Littérature scientifique sur le sujet « Central blood pressure levels »

Introduction: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are widely used in congestive heart failure and chronic kidney disease, but up to 40% of patients will experience aldosterone breakthrough, with aldosterone levels rising above pre-treatment levels after 6–12 months of renin-angiotensin-aldosterone system blockade. Aldosterone breakthrough has been associated with worsening congestive heart failure and chronic kidney disease, yet the pathophysiology remains unclear. Breakthrough has not been associated with elevated peripheral blood pressure, but no studies have assessed its effect on central blood pressure. Methods: Nineteen subjects with well-controlled peripheral blood pressure on stable doses of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker had aldosterone levels checked and central blood pressure parameters measured using the SphygmoCor system. The central blood pressure parameters of subjects with or without breakthrough, defined as serum aldosterone >15 ng/dl, were compared. Results: Of the 19 subjects, six had breakthrough with a mean aldosterone level of 33.8 ng/dl, and 13 were without breakthrough with a mean level of 7.1 ng/dl. There was no significant difference between the two groups in any central blood pressure parameter. Conclusions: We found no correlation between aldosterone breakthrough and central blood pressure. The clinical impact of aldosterone breakthrough likely depends on its non-genomic, pro-fibrotic, pro-inflammatory effects rather than its regulation of extracellular volume.

Background To eliminate the influence of hydrostatic pressure, proper transducer positions for central venous pressure and pulmonary artery wedge pressure are at the uppermost blood levels of right atrium (RA) and left atrium (LA). This study was performed to investigate accurate reference levels of central venous pressure and pulmonary artery wedge pressure in the supine position. Methods Chest computed tomography images of 96 patients without history of cardiothoracic surgery, heart disease, or cardiothoracic anatomical abnormality were retrospectively reviewed. The anteroposterior (AP) diameter of the thorax and the vertical distances from the skin on the back to the most anterior portion of RA (RA height) and LA (LA height) were measured. Their ratios were abbreviated, respectively, as RA height/AP diameter and LA height/AP diameter. Data are expressed as mean +/- SD (range). Results There was a significant difference [4.6 +/- 1.0 (1.6-6.4) cm; P < 0.001] between RA and LA heights. AP diameter was positively correlated with RA and LA heights (R = 0.839 and 0.700, respectively; P < 0.001). There was also a significant difference between RA height/AP diameter [0.83 +/- 0.03 (0.71-0.91)] and LA height/AP diameter [0.62 +/- 0.04 (0.52-0.72)] (P < 0.001). Conclusion In the supine position, a central venous pressure transducer should be positioned approximately 4.6 cm higher than a pulmonary artery wedge pressure transducer. The external reference level for central venous pressure seems to be at approximately four fifths of the AP diameter of the thorax from the back, and that for pulmonary artery wedge pressure seems to be at approximately three fifths of the AP diameter.

The study determines the peculiarities of the response of the central and peripheral links of to a cold stimulus in people with different levels of blood pressure (BP). The dynamics of blood pressure, heart rate, rheographic index and cardiorhythmography before and after the cold pressor test were evaluated. A significantly higher increase in systolic and diastolic BP in response to the cold pressor test was found in the persons with a normal high level of initial blood pressure (130/85–139/89 mm Hg) (p < 0.05). During the examination, a higher percentage of those with a hyperreactive blood pressure response was found (25%). In the experiment participants with initial blood pressure > 130/85 mm Hg a significant influence of the sympathetic nervous system on the cardiovascular system central and peripheral links in response to cold stress was observed. The individuals with normal (120/80– 129/84 mm Hg) and normal low (110/70-120/80 mm Hg) blood pressure showed a satisfactory response of the cardiovascular system to cold stress, so they should expect less health risks when working at low ambient temperatures.

Intraocular pressure (IOP), arterial blood pressure (PA), and cerebrospinal fluid (CSF) pressure have been identified as major players in several ocular pathologies, including glaucoma, central vein occlusion, and papilledema, to name a few. IOP, PA, and CSF pressures are not independent from each other. For example, aqueous humor and CSF flows, whose mechanics contribute to establish IOP and CSF pressure levels, originate from blood flow, which is driven by PA. As a consequence, it is difficult to experimentally isolate IOP, PA, and CSF pressure and to disentangle their effect in pathological conditions. Here we utilize a theoretical approach to address this issue.

Aim. To compare the relationships between conventional and new potentially more early investigational biomarkers (urine and ultrasound) of kidney injury and central aortic blood pressure, vascular stiffness and reactivity, endothelial dysfunction in patients with different severity of hypertension.Material and methods. Urine levels NGAL, KIM-1, L-FABP, albuminuria and serum levels of сystatin C and creatinine were measured in 92 hypertensive patients with mild and severe hypertension, 46 male (mean age 50,7±12,2 years). Glomerular filtration rate was estimated by the level of serum creatinine and cystatin C by MDRD and CKD-EPI formulas. Instrumental examination included measuring office blood pressure, 24-hour ambulatory blood pressure monitoring (SpaceLabs 90207), applanation tonometry (SphygmoCor, Artcor Medical) with the calculation of central aortic blood pressure, pulse wave velocity and augmentation index and Doppler ultrasonography with assessment of intraparenchymal renal arterial resistance indices — resistive index and pulsatility index (Vivid 7 dimension). Endothelial function was assessed by reactive hyperemia index with EndoPAT device (Itamar Medicals).Results. There were no differences in conventional levels of biomarkers between patients, however, cystatin C level increased and serum cystatin C estimated GFR and serum creatinine and cystatin C estimated GFR (CKD EPI formula) (sCr,Cys-estimated GFR) levels decreased with the severity of hypertension. These novel biomarkers were associated with increased central aortic blood pressure, arterial stiffness and intraparenchymal renal arterial resistance indices. Decreased sCr,Cys-estimated GFR levels were associated with lower reactive hyperemia index. There were no differences in NGAL, KIM-1 and L-FABP levels in patients with hypertension. However, NGAL levels were associated with increased augmentation index, resistive index in intralobular and pulsatility index in arcuate arteries, KIM-1 and L-FABP levels were associated with increased systolic and diastolic central aortic blood pressure, pulse wave velocity only in patients with severe and resistant hypertension.Conclusion. Serum cystatin C, NGAL, KIM-1 and L-FABP levels seem to be biomarkers of increased systemic and intrarenal vascular stiffness in patients with different severity of hypertension.

Resting blood volumes and arterial and central venous pressures (CVP) were measured in 14 men before and after exercise training to determine whether training-induced hypervolemia is accompanied by a change in total vascular capacitance. In addition, resting levels of plasma arginine vasopressin (AVP), atrial natriuretic peptide (ANP), aldosterone (Ald), and norepinephrine (NE) were measured. The same measurements were conducted in seven subjects who did not undergo exercise and acted as controls. Exercise training consisted of 10 wk of controlled cycle exercise for 30 min/day, 4 days/wk at 75-80% of maximal O2 uptake (VO2max). A training effect was verified by a 20% increase in VO2max, a resting bradycardia, and a 9% increase in blood volume. Mean arterial blood pressure was unaltered by exercise training, but resting CVP increased by 16% (P less than 0.05). The percent change in blood volume from before to after training was linearly related to the percent change in CVP (r = 0.903, P less than 0.05). As a consequence of elevations in both blood volume and CVP, the volume-to-pressure ratio was unchanged after exercise training. Plasma AVP, ANP, Ald, and NE were unaltered. Our results indicate that elevated CVP is a consequence of training-induced hypervolemia without alteration in total effective venous capacitance.

There is strong evidence from different types of studies, including the discrete infusion of agonists and antagonists and ablation of specific brain areas or transmitter-type neurons, that mineralocorticoids, in excess, act in the brain to elevate blood pressure. Aldosterone enhances the entry of Na+ through amiloride-sensitive Na+ channels in some mineralocorticoid-sensitive transport epithelial cells. To define possible cellular mechanisms involved in central mineralocorticoid action, benzamil, an amiloride analogue with selective affinity for the Na+ channel, was continuously infused intracerebroventricularly in three mineralocorticoid-dependent hypertension models in Sprague-Dawley rats, the continuous subcutaneous infusion of aldosterone, the intracerebroventricular infusion of aldosterone, and the ingestion of carbenoxolone, a synthetic licorice analogue. The intracerebroventricular infusion of 0.3 and 0.5 micrograms/h of benzamil, doses that did not have an adverse effect on growth and that had no effect on the blood pressure when infused subcutaneously, prevented the increase in blood pressure in these models. The infusion of these levels of benzamil had no effect on urine volume even in those animals in which it prevented an increase in blood pressure. These data suggest that the central effects of mineralocorticoids on blood pressure are mediated, at least in part, by the effects of mineralocorticoids on amiloride-sensitive sodium transport.

The integrated studies of central hemodynamics and vascular load of the heart in athletes of various specializations and skill levels are carried out over the last 30 years at RSUPE. However, data on the central hemodynamics and vascular load of the heart in highly skilled archers in the conditions of the draw are virtually absent. Determination of the vascular resistances (peripheral and elastic) during the draw is difficult because of the need of blood pressure measuring [4], it is virtually impossible since a typical way to draw both arms stiff. To simulate the draw, the authors have used the expander, one end of which is rigidly fixed, and stretching expander at the other end with one hand simulates the draw thus the second hand is free to measure blood pressure. It is shown that in the course of research the vascular resistances change in wide limits - from optimal normal levels to prehypertonic and hypertonic levels of their values. Thus, the systolic and diastolic pressures remain normal before stretching expander, and during the tensioning and recovery. With the increase in vascular resistance the values of the stroke and minute blood volumes are significantly reduced.

To the Editor.— We have read with great interest the recently published article by Perry et al.1 The need to define "safe" blood pressure levels in the critically ill premature infants is a central topic in the prevention of intracranial hemorrhage. However, in Perry's paper maximum systolic blood pressure and maximum mean blood pressure values are much higher than those reported by previously published articles.2-4 High blood pressure values were reported by Lou and Friis-Hansen5 in nine newborns.

Hemodynamic effects of insulin resistance (IR) are thought to be largely dependent on its relationship with body mass index (BMI) and blood pressure (BP) levels. The first part of the present thesis was aimed at exploring whether IR is associated with hemodynamic indices of cardiovascular function in a large sample of non-diabetic individuals from the general population (n=731) and if so, to explore if such relationship is continuous across different categories of BMI (lean, overweight and obese), and BP (normal BP, high-normal BP and hypertension). IR was assessed with the homeostasis model assessment of IR (HOMA-IR). Based on a value of HOMA-IR of 2.09 (75th percentile of distribution curve), subjects were classified as insulin-sensitive (IS, HOMA<2.09) or insulin-resistant (IR, HOMA≥2.09). Synchronized beat-to-beat recordings of stroke volume (impedance cardiography) and R-R interval (ECG), along with repeated BP measurements were performed over 5 minutes. Stroke index (SI), cardiac index (CI), systemic vascular resistance index (SVRI), left cardiac work index (LCWI), pre-ejection period (PEP) and left ventricular ejection time (LVET) were computed and averaged. In analysis of co-variance allowing for confounders, IR subjects showed significantly higher BP levels and SVRI, and reduced R-R interval, SI, CI, LCWI, PEP and LVET. These differences remained significant when analyses were performed within each BMI and BP category. Overall, these results indicate that effects of IR on hemodynamic indices of cardiovascular function are continuous across different BMI and BP categories, reinforcing the importance of IR in the pathogenesis of cardiovascular alterations beyond its association with obesity and hypertension. The finding of a significant association between IR and hemodynamic alterations even in lean and normotensive subjects was the rationale to explore potential mechanisms for these alterations in this selected group of subjects. Specific objectives of this second part of the thesis were: 1) To explore the relationship between insulin resistance and systemic hemodynamics, cardiac baroreflex sensitivity and indices of autonomic CV modulation. 2) To explore the relationship of insulin resistance with 24h heart rate, average blood pressure levels and blood pressure variability over the 24h; and 3) To explore the relationship of insulin resistance with central blood pressure levels and with measures of large artery stiffness and wave reflections. The study population for these analyses was constituted by subjects who were below the 30th percentile of diastolic blood pressure (DBP) distribution curve (DBP ≤72 mmHg) and who had no elevation in systolic BP levels. In addition, subjects were excluded in case of diabetes mellitus (fasting blood glucose ≥126 mg/dL or use of medications for previously diagnosed type 2 diabetes) obesity (BMI≥30) or taking medications with effects on BP. A total of 90 subjects fulfilling inclusion criteria were considered for the present analysis and underwent further assessments. Insulin resistance was assessed with HOMA-index and subjects classified into IR tertiles, based on the distribution of HOMA-index values. 24h Ambulatory BP monitoring was performed. Mean SBP and DBP were averaged for the day, night and 24h, and the respective day-to-night dipping was calculated. BPV was assessed for SBP and DBP as 24h standard deviation (SD), weighted 24h SD (wSD), daytime and night-time SD. Recordings of pulse waveform were obtained by means of a previously validated oscillometric device for ambulatory BP monitoring with in-built transfer-function like method. Aortic pulse wave velocity (PWV, m/s) and other measures derived from pulse wave analysis such as augmentation index (AIx, %), central SBP (cSBP), central DBP (cDBP) and central pulse pressure (cPP) were computed. Peripheral SBP and DBP, and heart rate (HR) were recorded and pulse pressure (PP) calculated as the difference between SBP and DBP. Non-invasive assessment of beat-to-beat BP, R-R interval (ECG) and stroke volume (by means of impedance cardiography) were performed during 10 min in supine position and specific hemodynamic indices associated with their measurement were computed and averaged: RRI (msec), heart rate (HR, bpm), stroke volume index (SI, mL/beat/m2), cardiac index (CI, L/min/m2), SBP (mmHg) and DBP (mmHg), systemic vascular resistance index (SVRI, dyn/sec/cm-5/m2), left cardiac work index (LCWI, Kg/m/m2), pre-ejection period (PEP, msec), left ventricular ejection time (LVET, msec) and PEP/LVET ratio were calculated. Cardiac autonomic modulation was assessed by computer analysis of 10 min beat-to-beat BP and ECG recordings in resting supine position. Cardiac baroreflex sensitivity (BRS) was estimated by sequence method. Total variance, low-frequency (LF) and high-frequency (HF) spectral components of HR variability (HRV) were assessed by autoregressive analysis. LF/HF ratio was calculated. After multiple regression analysis, adjusting for common confounders such as age, sex, HR and BMI, increasing values of HOMA-IR were associated with reduced RRI, SI, CI, and with increased SVRI, SBP and DBP. IR was also associated with reduced BRS (up, down, and total slopes), decreased parasympathetic indices of autonomic CV modulation (SDRRI, HF-power, total power) and a predominance of sympathetic component of HRV (increased LF/HF ratio). Increasing values of HOMA-IR were also associated with increased HR and average SBP levels (during day, night and 24-h period), with augmented BP variability (Day SBP SD, and SBP wSD) and with a reduced dipping of HR. Finally, insulin resistance was shown to be associated with increasing values of aortic PWV, and with higher central and peripheral SBP and DBP levels. Overall, these results support significant associations between insulin resistance and changes in hemodynamic and autonomic indices of cardiovascular function, even after accounting for common confounders. These findings suggest that in normotensive healthy adults, increases in insulin resistance may promote alterations in autonomic cardiovascular modulation, in systemic hemodynamics and in arterial stiffness, all of which are known contributors to the pathogenesis of hypertension.

Central aortic systolic blood pressure (cSBP) differs from peripheral systolic blood pressure (pSBP) measured in the arm. cSBP may be estimated non-invasively by application of a generalised transfer function (GIF) to a high fidelity peripheral arterial waveform or from the late systolic shoulder (SBP2) of such a waveform. The relative accuracy of these estimates and the degree to which they depend on the accuracy of peripheral blood pressure is unknown. The interest in estimates of central blood pressure is driven in large part by the fact that aortic pulse pressure (cPP) is thought to be a better predictor of cardiovascular risk and response to antihypertensive treatment than peripheral BP. However, little is known concerning the mechanism by which drugs may reduce cPP independently of effects on peripheral BP. Objectives of this thesis were to: 1. Examine the relative accuracy of different methods (GTF and SBP2) for estimating cSBP and cPP from a high fidelity peripheral arterial waveform. 2. Determine errors introduced by non-invasive calibration of this waveform (as would be the case when such methods are used in practice), 3. Explore the use of a simplified method for estimating cSBP based upon pressure oscillations within an arm cuff. 4. Determine the mechanism by which nitroglycerin (NTG, a drug that has relatively selective actions to lower cSBP) lowers cPP. Pressure and in some cases combined pressure and flow velocity were acquired at the aortic root during cardiac catheterisation. Peripheral blood pressure was measured by oscillometry and peripheral blood pressure waveforms were obtained from blood pressure cuffs, radial tonometry and a servo-controlled finger cuff. To address objective 4 additional measurements of ventricular and arterial mechanics where made using ultrasound and magnetic resonance imaging.

Background High blood pressure is associated with an increased risk of cardiovascular disease and premature death. The shape of association between blood pressure and the risk of cardiovascular events is debated. Some researchers suggest that the association is linear or log-linear, whereas others suggest it is J-shaped. Randomized controlled trials of antihypertensive treatment have been successful in hypertension, but ambiguous in the high normal blood pressure range. Previous systematic reviews have not found any interaction between baseline systolic blood pressure and treatment effect, with beneficial effects at systolic blood pressure levels well below what is currently recommended. These reviews, however, use a method to standardize treatment effects and study weights according to within-trial blood pressure differences that may introduce bias. Methods We performed two systematic reviews to assess the effect of antihypertensive treatment on cardiovascular disease and mortality at different blood pressure levels. The first review was limited to people with diabetes mellitus. The second review included all patient categories except those with heart failure and acute myocardial infarction. Both reviews were designed with guidance from Cochrane Collaborations Handbook for Systematic Reviews of Interventions, and are reported according to PRISMA guidelines. We included randomized controlled trials assessing any antihypertensive agent against placebo or any blood pressure targets against each other. Results were combined in random-effects meta-analyses, stratified by baseline systolic blood pressure. Non-stratified analyses were performed for coronary heart disease trials and post-stroke trials. Interaction between blood pressure level and treatment effect was assessed with Cochran’s Q in the first review, and multivariable-adjusted metaregression in the second review. The third paper builds on data from the second paper, and assesses the effect of standardization according to within-trial blood pressure differences on the results of meta-analyses. We performed non-standardized analyses, analyses with standardized treatment effects, and analyses with standardized treatment effects and standard errors. We compared treatment effect measures and heterogeneity across different methods of standardization. We also compared treatment effect estimates between fixed-effects and random-effects meta-analyses within each method of standardization. Lastly, we assessed the association between number of events and study weights, using linear regression. Results Forty-nine trials assessed the effect of antihypertensive treatment in people with diabetes mellitus. Treatment effect on cardiovascular mortality and myocardial infarction decreased with lower baseline systolic blood pressure. Treatment reduced the risk of death and cardiovascular disease if baseline systolic blood pressure was 140 mm Hg or higher. If baseline systolic blood pressure was below 140 mm Hg, however, treatment increased the risk of cardiovascular death by 15 % (0-32 %). Fifty-one trials assessed the effect of antihypertensive treatment in primary prevention. Treatment effect on cardiovascular mortality, major cardiovascular events, and heart failure decreased with lower baseline systolic blood pressure. If baseline systolic blood pressure was 160 mm Hg or higher treatment reduced the risk of major cardiovascular events by 22 % (95 % confidence interval 13-30 %). If systolic blood pressure was 140-159 mm Hg treatment reduced the risk by 12 % (4-20 %), whereas if systolic blood pressure was below 140 mm Hg, treatment effect was neutral (4 % increase to 10 % reduction). All-cause mortality was reduced if systolic blood pressure was 140 mm Hg or higher, with neutral effect at lower levels. Twelve trials compared antihypertensive treatment against placebo in people with coronary heart disease. Mean baseline systolic blood pressure was 138 mm Hg. Treatment reduced the risk of major cardiovascular events by 10 % (3-16 %), whereas the effect on mortality was neutral (7 % increase to 11 % reduction). Standardization of treatment effects resulted in more extreme effect estimates for individual trials. This caused increased between-study heterogeneity, and different results with fixed- and random-effects model. Standardization of standard errors shifted weights from trials with many events to trials with large blood pressure differences. This caused biased overall effect estimates. Standardization of standard errors also resulted in wider confidence intervals, masking the previously increased heterogeneity. This reduced the possibility to find different treatment effects at different blood pressure levels. Conclusion The effect of antihypertensive treatment depends on blood pressure level before treatment. Treatment reduces the risk of death and cardiovascular disease if baseline systolic blood pressure is 140 mm Hg or higher. Below this level, treatment is potentially harmful in people with diabetes, has neutral effect in primary prevention, but might offer additional protection in people with coronary heart disease. Standardization should generally be avoided in meta-analyses of antihypertensive treatment. Previous meta-analyses using standardized methods should be interpreted with caution.
Hjärt-kärlsjukdomar leder till fler dödsfall och fler förlorade levnadsår än någon annan sjukdomsgrupp. Den enskilt viktigaste riskfaktorn som bidrar till hjärtkärlsjukdomar ur ett befolkningsperspektiv är högt blodtryck. Risken att drabbas av hjärt-kärlsjukdomar minskar om man behandlar högt blodtryck men till vilken nivå blodtrycket skall behandlas är kontroversiellt. Denna avhandling innefattar två systematiska översikter och meta-analyser samt ett arbete som jämför olika sätt att hantera skillnader mellan studier i meta-analyser. De systematiska översikterna sammanställer data från randomiserade kontrollerade studier av blodtryckssänkande behandling. Vår övergripande frågeställning var om effekten av behandling påverkas av blodtrycksnivån innan behandling. Mer specifikt studerades hur behandling påverkade risken att dö eller drabbas av hjärt-kärlsjukdom vid olika blodtrycksnivåer. Det första arbetet fokuserade på personer med diabetes. För dessa fann vi att blodtryckssänkande behandling minskar risken att dö eller drabbas av hjärtkärlsjukdom vid nivåer ≥ 140 mmHg. Vi fann ingen nytta, men möjligen en skadlig effekt av behandling, vid lägre blodtrycksnivåer. Det andra arbetet inkluderade studier oberoende av vilka sjukdomar deltagarna hade. Vi fann att den förebyggande effekten av blodtryckssänkande behandling berodde på blodtrycksnivån. Vid blodtryck > 160 mmHg minskade risken att drabbas av hjärt-kärlsjukdomar med 22 % hos de som erhöll behandling. Om blodtrycket var 140-160 mmHg minskade risken med 12 %, men om blodtrycket var < 140 mmHg sågs ingen behandlingseffekt. Hos personer med känd kranskärlssjukdom, och ett medelblodtryck på 138 mmHg, fann vi en något minskad risk för hjärt-kärlhändelser med ytterligare behandling. I det tredje arbetet fann vi att skillnader i resultat mellan olika studier inte kan antas bero endast på olika grad av blodtryckssänkning i studierna. När resultaten standardiserades, som om alla studier hade sänkt blodtrycket lika mycket, ökade nämligen skillnaderna mellan studierna. Detta resulterade i sin tur i snedvridning av resultaten från meta-analyser av standardiserade värden. Sammanfattningsvis minskar blodtryckssänkande behandling risken att dö eller drabbas av hjärt-kärlsjukdomar om blodtrycket är 140 mmHg eller högre. Vid lägre nivåer är nyttan med behandling osäker samtidigt som det finns potentiella risker. Standardisering bör inte användas rutinmässigt vid metaanalyser av blodtrycksstudier. Tidigare meta-analyser som använt denna metod bör tolkas med försiktighet.

African Americans disproportionately develop cardiovascular disease risk factors including high blood pressure and high cholesterol levels in comparison to European Americans. The purpose of this study was to examine the associations of diet quality and physical activity with blood pressure levels and cholesterol levels among African Americans. The social ecological model was the theoretical foundation for the study. Research questions were designed to examine the extent to which diet quality and physical activity predict blood pressure levels and cholesterol levels. The research design was quantitative cross-sectional secondary analysis of 959 participants. After controlling for demographic factors, body mass index, and energy intake, there was a potential nonlinear association between the dietary approaches to stop hypertension (DASH) diet and blood pressure levels. Multivariable-adjusted logistic regression analysis showed that a fourth-quintile DASH score significantly predicted blood pressure (OR: 0.57; 95% CI [0.35, 0.93]). There was no association between the DASH diet and cholesterol levels. Physical activity was not significantly associated with blood pressure levels or cholesterol levels. Researchers can use these findings to replicate large prospective studies. In addition, findings may be used to promote positive social change by healthcare professionals including dieticians and clinicains, as well as health promotion advocates and other institutions or individuals with public health interest.

Background: In patients with diabetes, high blood pressure is an established risk factor for cardiovascular disease. The aim of this thesis was to explore the associations between blood pressure levels measured with different techniques and during different circumstances, and the degree of cardiovascular organ damage and subsequent prognosis in patients with diabetes. Methods: We analysed baseline data from patients with type 2 diabetes who participated in the observational cohort study CARDIPP (Cardiovascular Risk factors in Patients with Diabetes – a Prospective study in Primary care), and longitudinal data from patients registered in the Swedish national quality registry RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive care Admissions). Patients in CARDIPP underwent nurse-recorded, 24-hour ambulatory and non-invasive central blood pressure measurements. Patients in RIKS-HIA had their systolic blood pressure measured upon hospitalisation for acute chest pain. Results: In CARDIPP, nearly one in three patients with office normotension (<130/80 mmHg) were hypertensive during the night (≥120/70 mmHg). This phenomenon, masked nocturnal hypertension, was significantly associated with increased arterial stiffness and increased central blood pressure. Furthermore, nearly one in five CARDIPP patients with office normotension had high central pulse pressure (≥50 mmHg), and there was a significant association between high central pulse pressure and increased carotid intima-media thickness and increased arterial stiffness. Among CARDIPP patients who used at least one antihypertensive drug, those who used beta blockers had significantly higher central pulse pressure than those who used other antihypertensive drugs, but there were no significant between-group differences concerning office or ambulatory pulse pressures. In CARDIPP patients with or without antihypertensive treatment, ambulatory systolic blood pressure levels were significantly associated with left ventricular mass, independently of central systolic blood pressure levels. When RIKS-HIA patients, admitted to hospital for chest pain, were stratified in quartiles according to admission systolic blood pressure levels, the risk for all-cause one-year mortality was significantly lower in patients with admission systolic blood pressure in the highest quartile (≥163 mmHg) than in patients with admission systolic blood pressure in the reference quartile (128-144 mmHg). This finding remained unaltered when the analysis was restricted to include only patients with previously known diabetes. Conclusions: In patients with type 2 diabetes, ambulatory or central blood pressure measurements identified patients with residual risk factors despite excellent office blood pressure control or despite ongoing antihypertensive treatment. Ambulatory systolic blood pressure predicted left ventricular mass independently of central systolic blood pressure. In patients with previously known diabetes who were hospitalised for acute chest pain, there was an inverse relationship between systolic blood pressure measured at admission and the risk for one-year all-cause mortality.

With the rise in prevalence of cardiovascular (CV) disease, risk stratification is becoming increasingly important. Accurate characterization of the CV system is required, for which central aortic blood pressure (BP) parameters form an integral part. However, invasive measurement of central aortic BP parameters (aP) is difficult. Therefore, non-invasive methods to estimate aP from the radial pressure pulse (rPulse) have been proposed. To analyze accuracy of estimated aP (aPhat) and applicability in risk stratification and diagnosis, this study presents: (1) a novel representation of the rPulse with minimal loss of information, (2) a framework for strict definition and statistical analysis of aPhat, and (3) a dynamic analysis of effects of mean BP (MP) and heart rate (HR) in the rPulse shape. Methods: (1) 2671 rPulse s measured by applanation tonometry were represented using the first eight principal components (PC) scores after standard PC transformation. rPulse shapes were compared in three subpopulations. (2) The concept of "estimation option" (EO) for aP estimation was presented. A framework for strict definition of aPhat and the comparison of EOs was proposed, and 7 different EOs compared. (3) A sequence of rPulse s was analyzed during soft exhalation maneuver (SEM) %, a mild Valsalva type maneuver, in eight healthy subjects. Radial BP and respiration pressure were continuously measured. The effects of MP and HR in the rPulse parameters were analyzed by standard linear regression for each subject. Results: (1) PC representation of the rPulse improves accuracy of the estimation of aPhat compared with the simple use of rPulse parameters. Subpopulations have distinctive rPulse shapes. (2) No single EO was better for the estimation of all aPhat. Inclusion of MP improves estimation accuracy. Despite further improvement when rPulse is included, the general transfer function EO is a biased estimator. (3) The dynamic analysis of the rPulse provides information of the effects of MP and HR in the rPulse not available in static analysis. The effects were specific for each individual and different from the results obtained from a general population. Conclusions: For accurate CV risk stratification, future studies should include a dynamic measurement of calibrated radial pressure pulse during SEM maneuver. Risk analysis and diagnosis should be based on representations of the rPulse with minimum loss of information. aPhat should be used for better understanding of the underlying physiological principles.

Central venous pressure (CVP) is at the crucial intersection of the force returning blood to the heart and the force produced by cardiac function, which drives the blood back to the systemic circulation. The normal range of CVP is small so that before using it one must ensure proper measurement, specifically the reference level. A useful approach to hypotension is to first determine if arterial pressure is low because of a decrease in vascular resistance or a decrease in cardiac output. This is done by either measuring cardiac output or making a clinical assessment blood flow. If the cardiac output is decreased, next determine whether this is because of a cardiac pump problem or a return problem. It is at this stage that the CVP is most helpful for these options can be separated by considering the actual CVP or even better, how it changed with the change in cardiac output. A high CVP is indicative of a primary pump problem, and a low CVP and return problem. Understanding the factors that determine CVP magnitude, mechanisms that produce the components of the CVP wave form and changes in CVP with respiratory efforts can also provide useful clinical information. In many patients, CVP can be estimated on physical exam.

ABSTRACT Background: Maternal mortality in Indonesia is caused by multifactors that are both direct and indirect factors. Complications during pregnancy and after delivery, including preeclampsia is the direct cause of 90% of maternal deaths. This case report aimed to describe the anaesthesia management on the incidence of severe preeclampsia to prevent the complications. Subjects and Method: We reported a 33-year-old G3P2A0 woman with 33 weeks of gestational age, diagnosed with severe pre-eclampsia partial HELLP syndrome, fetal dis-tress, type II diabetes mellitus pro SCTP emergency with physical status ASA II. Regional anaesthesia with sub-arachnoid block was performed by using Lidodex 75 mg and fentanyl 25 mcg intrathecally. Results: From the operation process, a baby boy with birth weight 2.900 gram and APGAR Score 7-8-9 was born. Two-hour post operation examination on patient showed compos mentis (consciousness), blood pressure 121/ 80 mmHg, heart rate 64 bpm, respiration rate 20 breath per minute, blood oxygen saturation levels (SpO2) 99% with 3 L/min nasal cannula. Patient was administered to HCU post operation to be monitored vital sign and signs of impending eclampsia. Post-operative refeeding was performed after bowel sound was positive. Conclusion: Selection of appropriate anaesthetic management in severe preeclampsia cases can prevent complications. Keywords: severe preeclampsia, sectio caesaria, regional anesthesia, subarachnoid block Correspondence: R. Th. Supraptomo. Department of Anaesthesiology and Intensive Therapy Dr. Moewardi Hospital. Jl Kolonel Sutarto 132 Jebres, Surakarta, Central Java, 57126. Email: ekasatrio-@gmail.com. Mobile: +6281329025599. DOI: https://doi.org/10.26911/the7thicph.05.29

Introduction: Breast cancer (BC) is one of the most prevalent cancers and considered one of the main causes of death among women worldwide. The genetic contribution to the incidence of BC is of great relevance, however, modifiable risk factors seem to be related to the development of this neoplasm. Several studies have provided evidence on the role of blood pressure (BP) levels in the carcinogenesis process. Goals assess the association between BP levels and the occurrence of BC. Methods: This is a case-control study nested in a cohort conducted between December 2013 and August 2014 in a municipality in the south of Brazil. Patients referred to oncology referral centers before starting adjuvant or neoadjuvant therapy for BC participated in the study. The control group was composed of women who visited the gynecology clinic during the same period. For each newly diagnosed case of BC, a control matched for age (±5 years) and menopausal status was included. Data were obtained through measurements with standardized techniques of BP levels and waist circumference (WC) measurement. Individuals with systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 85 mmHg were considered to have altered blood pressure. Results: Eighty two patients with BC and 82 controls (n=164) were evaluated. Slightly different characteristics were found between the two groups: skin color (p=0.097), months of breastfeeding (p=0.185) and physical activity (p=0.160). These variables were included in the adjusted analysis. Regarding the BP measurement, patients with SBP ≥130 mmHg and with DBP ≥85 mmHg were 7.30 and 4.56 times more likely to have MF (Malignant), respectively (95%CI 2.43–21.91, p <0.001 and 95%CI 1.82–11.44, p=0.003). This relationship remained significant after adjustment for WC ≥80 cm (OR = 6.75, 95%CI 2.22–20.54 and OR=6.75, 95%CI 1.67–10.81). Conclusions: The results of this study corroborate the current findings in the literature, showing evidence of an association between BP and BC levels. BP assessment, already incorporated into clinical practice and considered a predictor of several comorbidities, may gain additional importance in the female population as a modifiable risk factor for the prevention of BC. Thus, the importance of interventions in the management of BP levels in this population is elucidated.

Review question / Objective: Hypertension is a major risk factor for cardiovascular disease, which remains the leading cause of mortality worldwide. Urban environment as an possible cause of hypertension has received great attention. We aimed to systematically review the associations between greenspace and blood pressure (BP) levels/hypertension and use a meta-analysis to quantify the effects of greenspace on BP levels/hypertension. Condition being studied: Many epidemiological studies have assessed associations of greenspace with blood pressure levels and/or the prevalence of hypertension, whereas the results was inconsistent with some studies showing positive association but the others reporting null or negative associations. Systematic review and meta-analysis was conducted to synthesize data quantitatively across studies based on the primary outcome.

Review question / Objective: Would meditation programs affect fasting blood glucose levels and HbA(1c) of patients with type 2 diabetes mellitus? Would meditation programs intervention be of benefit for remission of depression and anxiety level? Would meditation programs improve quality of life of individuals with type 2 diabetes？ Do meditation programs affect body mass index (BMI), serum lipid levels and level of blood pressure? Which type of meditation programs is better for type 2 diabetes patients? Are there any differences of efficacy among different meditation programs? To provide valid evidence for the effect of meditation programs for type 2 diabetes by synthesizing and comparing outcomes from clinical trials. Main outcome(s): The outcomes include fasting blood glucose levels and HbA(1c).

In Israel and in the U.S., Streptococcus iniae is responsible for considerable losses in various fish species. Poor understanding of its virulence factors and limited know-how-to of vaccine formulation and administration are the main reasons for the limited efficacy of vaccines. Our strategy was that in order to Improve control measures, both aspects should be equally addressed. Our proposal included the following objectives: (i) construction of host-pathogen interaction models; (ii) characterization of virulence factors and immunodominant antigens, with assessment of their relative importance in terms of protection and (iii) genetic identification of virulence factors and genes, with evaluation of the protective effect of recombinant proteins. We have shown that two different serotypes are involved. Their capsular polysaccharides (CPS) were characterized, and proved to play an important role in immune evasion and in other consequences of the infection. This is an innovative finding in fish bacteriology and resembles what, in other fields, has become apparent in the recent years: S. iniae alters surface antigens. By so doing, the pathogen escapes immune destruction. Immunological assays (agar-gel immunodiffusion and antibody titers) confirmed that only limited cross recognition between the two types occurs and that capsular polysaccharides are immunodominant. Vaccination with purified CPS (as an acellular vaccine) results in protection. In vitro and ex-vivo models have allowed us to unravel additional insights of the host-pathogen interactions. S. iniae 173 (type II) produced DNA fragmentation of TMB-8 cells characteristic of cellular necrosis; the same isolate also prevented the development of apoptosis in NCC. This was determined by finding reduced expression of phosphotidylserine (PS) on the outer membrane leaflet of NCC. NCC treated with this isolate had very high levels of cellular necrosis compared to all other isolates. This cellular pathology was confirmed by observing reduced DNA laddering in these same treated cells. Transmission EM also showed characteristic necrotic cellular changes in treated cells. To determine if the (in vitro) PCD/apoptosis protective effects of #173 correlated with any in vivo activity, tilapia were injected IV with #173 and #164 (an Israeli type I strain). Following injection, purified NCC were tested (in vitro) for cytotoxicity against HL-60 target cells. Four significant observations were made : (i) fish injected with #173 had 100-400% increased cytotoxicity compared to #164 (ii) in vivo activation occurred within 5 minutes of injection; (iii) activation occurred only within the peripheral blood compartment; and (iv) the isolate that protected NCC from apoptosis in vitro caused in vivo activation of cytotoxicity. The levels of in vivo cytotoxicity responses are associated with certain pathogens (pathogen associated molecular patterns/PAMP) and with the tissue of origin of NCC. NCC from different tissue (i.e. PBL, anterior kidney, spleen) exist in different states of differentiation. Random amplified polymorphic DNA (RAPD) analysis revealed the "adaptation" of the bacterium to the vaccinated environment, suggesting a "Darwinian-like" evolution of any bacterium. Due to the selective pressure which has occurred in the vaccinated environment, type II strains, able to evade the protective response elicited by the vaccine, have evolved from type I strains. The increased virulence through the appropriation of a novel antigenic composition conforms with pathogenic mechanisms described for other streptococci. Vaccine efficacy was improved: water-in-oil formulations were found effective in inducing protection that lasted for a period of (at least) 6 months. Protection was evaluated by functional tests - the protective effect, and immunological parameters - elicitation of T- and B-cells proliferation. Vaccinated fish were found to be resistant to the disease for (at least) six months; protection was accompanied by activation of the cellular and the humoral branches.

Objectives. Although the health benefits of physical activity are well described for the general population, less is known about the benefits and harms of physical activity in people dependent upon, partially dependent upon, or at risk for needing a wheelchair. This systematic review summarizes the evidence for physical activity in people with multiple sclerosis, cerebral palsy, and spinal cord injury regardless of current use or nonuse of a wheelchair. Data sources. We searched MEDLINE®, CINAHL®, PsycINFO®, Cochrane CENTRAL, Embase®, and Rehabilitation and Sports Medicine Source from 2008 through November 2020, reference lists, and clinical trial registries. Review methods. Predefined criteria were used to select randomized controlled trials, quasiexperimental nonrandomized trials, and cohort studies that addressed the benefits and harms of observed physical activity (at least 10 sessions on 10 different days of movement using more energy than rest) in participants with multiple sclerosis, cerebral palsy, and spinal cord injury. Individual study quality (risk of bias) and the strength of bodies of evidence for key outcomes were assessed using prespecified methods. Dual review procedures were used. Effects were analyzed by etiology of impairment and physical activity modality, such as treadmill, aquatic exercises, and yoga, using qualitative, and when appropriate, quantitative synthesis using random effects meta-analyses. Results. We included 146 randomized controlled trials, 15 quasiexperimental nonrandomized trials, and 7 cohort studies (168 studies in 197 publications). More studies enrolled participants with multiple sclerosis (44%) than other conditions, followed by cerebral palsy (38%) and spinal cord injury (18%). Most studies were rated fair quality (moderate risk of bias). The majority of the evidence was rated low strength. • In participants with multiple sclerosis, walking ability may be improved with treadmill training and multimodal exercise regimens that include strength training; function may be improved with treadmill training, balance exercises, and motion gaming; balance is likely improved with postural control exercises (which may also reduce risk of falls) and may be improved with aquatic exercises, robot-assisted gait training, treadmill training, motion gaming, and multimodal exercises; activities of daily living may be improved with aquatic therapy; sleep may be improved with aerobic exercises; aerobic fitness may be improved with multimodal exercises; and female sexual function may be improved with aquatic exercise. • In participants with cerebral palsy, balance may be improved with hippotherapy and motion gaming, and function may be improved with cycling, treadmill training, and hippotherapy. • In participants with spinal cord injury, evidence suggested that activities of daily living may be improved with robot-assisted gait training. • When randomized controlled trials were pooled across types of exercise, physical activity interventions were found to improve walking in multiple sclerosis and likely improve balance and depression in multiple sclerosis. Physical activity may improve function and aerobic fitness in people with cerebral palsy or spinal cord injury. When studies of populations with multiple sclerosis and cerebral palsy were combined, evidence indicated dance may improve function. • Evidence on long-term health outcomes was not found for any analysis groups. For intermediate outcomes such as blood pressure, lipid profile, and blood glucose, there was insufficient evidence from which to draw conclusions. There was inadequate reporting of adverse events in many trials. Conclusions. Physical activity was associated with improvements in walking ability, general function, balance (including fall risk), depression, sleep, activities of daily living, female sexual function, and aerobic capacity, depending on population enrolled and type of exercise utilized. No studies reported long-term cardiovascular or metabolic disease health outcomes. Future trials could alter these findings; further research is needed to examine health outcomes, and to understand the magnitude and clinical importance of benefits seen in intermediate outcomes.

1.1 Macroeconomic summary Economic recovery has consistently outperformed the technical staff’s expectations following a steep decline in activity in the second quarter of 2020. At the same time, total and core inflation rates have fallen and remain at low levels, suggesting that a significant element of the reactivation of Colombia’s economy has been related to recovery in potential GDP. This would support the technical staff’s diagnosis of weak aggregate demand and ample excess capacity. The most recently available data on 2020 growth suggests a contraction in economic activity of 6.8%, lower than estimates from January’s Monetary Policy Report (-7.2%). High-frequency indicators suggest that economic performance was significantly more dynamic than expected in January, despite mobility restrictions and quarantine measures. This has also come amid declines in total and core inflation, the latter of which was below January projections if controlling for certain relative price changes. This suggests that the unexpected strength of recent growth contains elements of demand, and that excess capacity, while significant, could be lower than previously estimated. Nevertheless, uncertainty over the measurement of excess capacity continues to be unusually high and marked both by variations in the way different economic sectors and spending components have been affected by the pandemic, and by uneven price behavior. The size of excess capacity, and in particular the evolution of the pandemic in forthcoming quarters, constitute substantial risks to the macroeconomic forecast presented in this report. Despite the unexpected strength of the recovery, the technical staff continues to project ample excess capacity that is expected to remain on the forecast horizon, alongside core inflation that will likely remain below the target. Domestic demand remains below 2019 levels amid unusually significant uncertainty over the size of excess capacity in the economy. High national unemployment (14.6% for February 2021) reflects a loose labor market, while observed total and core inflation continue to be below 2%. Inflationary pressures from the exchange rate are expected to continue to be low, with relatively little pass-through on inflation. This would be compatible with a negative output gap. Excess productive capacity and the expectation of core inflation below the 3% target on the forecast horizon provide a basis for an expansive monetary policy posture. The technical staff’s assessment of certain shocks and their expected effects on the economy, as well as the presence of several sources of uncertainty and related assumptions about their potential macroeconomic impacts, remain a feature of this report. The coronavirus pandemic, in particular, continues to affect the public health environment, and the reopening of Colombia’s economy remains incomplete. The technical staff’s assessment is that the COVID-19 shock has affected both aggregate demand and supply, but that the impact on demand has been deeper and more persistent. Given this persistence, the central forecast accounts for a gradual tightening of the output gap in the absence of new waves of contagion, and as vaccination campaigns progress. The central forecast continues to include an expected increase of total and core inflation rates in the second quarter of 2021, alongside the lapse of the temporary price relief measures put in place in 2020. Additional COVID-19 outbreaks (of uncertain duration and intensity) represent a significant risk factor that could affect these projections. Additionally, the forecast continues to include an upward trend in sovereign risk premiums, reflected by higher levels of public debt that in the wake of the pandemic are likely to persist on the forecast horizon, even in the context of a fiscal adjustment. At the same time, the projection accounts for the shortterm effects on private domestic demand from a fiscal adjustment along the lines of the one currently being proposed by the national government. This would be compatible with a gradual recovery of private domestic demand in 2022. The size and characteristics of the fiscal adjustment that is ultimately implemented, as well as the corresponding market response, represent another source of forecast uncertainty. Newly available information offers evidence of the potential for significant changes to the macroeconomic scenario, though without altering the general diagnosis described above. The most recent data on inflation, growth, fiscal policy, and international financial conditions suggests a more dynamic economy than previously expected. However, a third wave of the pandemic has delayed the re-opening of Colombia’s economy and brought with it a deceleration in economic activity. Detailed descriptions of these considerations and subsequent changes to the macroeconomic forecast are presented below. The expected annual decline in GDP (-0.3%) in the first quarter of 2021 appears to have been less pronounced than projected in January (-4.8%). Partial closures in January to address a second wave of COVID-19 appear to have had a less significant negative impact on the economy than previously estimated. This is reflected in figures related to mobility, energy demand, industry and retail sales, foreign trade, commercial transactions from selected banks, and the national statistics agency’s (DANE) economic tracking indicator (ISE). Output is now expected to have declined annually in the first quarter by 0.3%. Private consumption likely continued to recover, registering levels somewhat above those from the previous year, while public consumption likely increased significantly. While a recovery in investment in both housing and in other buildings and structures is expected, overall investment levels in this case likely continued to be low, and gross fixed capital formation is expected to continue to show significant annual declines. Imports likely recovered to again outpace exports, though both are expected to register significant annual declines. Economic activity that outpaced projections, an increase in oil prices and other export products, and an expected increase in public spending this year account for the upward revision to the 2021 growth forecast (from 4.6% with a range between 2% and 6% in January, to 6.0% with a range between 3% and 7% in April). As a result, the output gap is expected to be smaller and to tighten more rapidly than projected in the previous report, though it is still expected to remain in negative territory on the forecast horizon. Wide forecast intervals reflect the fact that the future evolution of the COVID-19 pandemic remains a significant source of uncertainty on these projections. The delay in the recovery of economic activity as a result of the resurgence of COVID-19 in the first quarter appears to have been less significant than projected in the January report. The central forecast scenario expects this improved performance to continue in 2021 alongside increased consumer and business confidence. Low real interest rates and an active credit supply would also support this dynamic, and the overall conditions would be expected to spur a recovery in consumption and investment. Increased growth in public spending and public works based on the national government’s spending plan (Plan Financiero del Gobierno) are other factors to consider. Additionally, an expected recovery in global demand and higher projected prices for oil and coffee would further contribute to improved external revenues and would favor investment, in particular in the oil sector. Given the above, the technical staff’s 2021 growth forecast has been revised upward from 4.6% in January (range from 2% to 6%) to 6.0% in April (range from 3% to 7%). These projections account for the potential for the third wave of COVID-19 to have a larger and more persistent effect on the economy than the previous wave, while also supposing that there will not be any additional significant waves of the pandemic and that mobility restrictions will be relaxed as a result. Economic growth in 2022 is expected to be 3%, with a range between 1% and 5%. This figure would be lower than projected in the January report (3.6% with a range between 2% and 6%), due to a higher base of comparison given the upward revision to expected GDP in 2021. This forecast also takes into account the likely effects on private demand of a fiscal adjustment of the size currently being proposed by the national government, and which would come into effect in 2022. Excess in productive capacity is now expected to be lower than estimated in January but continues to be significant and affected by high levels of uncertainty, as reflected in the wide forecast intervals. The possibility of new waves of the virus (of uncertain intensity and duration) represents a significant downward risk to projected GDP growth, and is signaled by the lower limits of the ranges provided in this report. Inflation (1.51%) and inflation excluding food and regulated items (0.94%) declined in March compared to December, continuing below the 3% target. The decline in inflation in this period was below projections, explained in large part by unanticipated increases in the costs of certain foods (3.92%) and regulated items (1.52%). An increase in international food and shipping prices, increased foreign demand for beef, and specific upward pressures on perishable food supplies appear to explain a lower-than-expected deceleration in the consumer price index (CPI) for foods. An unexpected increase in regulated items prices came amid unanticipated increases in international fuel prices, on some utilities rates, and for regulated education prices. The decline in annual inflation excluding food and regulated items between December and March was in line with projections from January, though this included downward pressure from a significant reduction in telecommunications rates due to the imminent entry of a new operator. When controlling for the effects of this relative price change, inflation excluding food and regulated items exceeds levels forecast in the previous report. Within this indicator of core inflation, the CPI for goods (1.05%) accelerated due to a reversion of the effects of the VAT-free day in November, which was largely accounted for in February, and possibly by the transmission of a recent depreciation of the peso on domestic prices for certain items (electric and household appliances). For their part, services prices decelerated and showed the lowest rate of annual growth (0.89%) among the large consumer baskets in the CPI. Within the services basket, the annual change in rental prices continued to decline, while those services that continue to experience the most significant restrictions on returning to normal operations (tourism, cinemas, nightlife, etc.) continued to register significant price declines. As previously mentioned, telephone rates also fell significantly due to increased competition in the market. Total inflation is expected to continue to be affected by ample excesses in productive capacity for the remainder of 2021 and 2022, though less so than projected in January. As a result, convergence to the inflation target is now expected to be somewhat faster than estimated in the previous report, assuming the absence of significant additional outbreaks of COVID-19. The technical staff’s year-end inflation projections for 2021 and 2022 have increased, suggesting figures around 3% due largely to variation in food and regulated items prices. The projection for inflation excluding food and regulated items also increased, but remains below 3%. Price relief measures on indirect taxes implemented in 2020 are expected to lapse in the second quarter of 2021, generating a one-off effect on prices and temporarily affecting inflation excluding food and regulated items. However, indexation to low levels of past inflation, weak demand, and ample excess productive capacity are expected to keep core inflation below the target, near 2.3% at the end of 2021 (previously 2.1%). The reversion in 2021 of the effects of some price relief measures on utility rates from 2020 should lead to an increase in the CPI for regulated items in the second half of this year. Annual price changes are now expected to be higher than estimated in the January report due to an increased expected path for fuel prices and unanticipated increases in regulated education prices. The projection for the CPI for foods has increased compared to the previous report, taking into account certain factors that were not anticipated in January (a less favorable agricultural cycle, increased pressure from international prices, and transport costs). Given the above, year-end annual inflation for 2021 and 2022 is now expected to be 3% and 2.8%, respectively, which would be above projections from January (2.3% and 2,7%). For its part, expected inflation based on analyst surveys suggests year-end inflation in 2021 and 2022 of 2.8% and 3.1%, respectively. There remains significant uncertainty surrounding the inflation forecasts included in this report due to several factors: 1) the evolution of the pandemic; 2) the difficulty in evaluating the size and persistence of excess productive capacity; 3) the timing and manner in which price relief measures will lapse; and 4) the future behavior of food prices. Projected 2021 growth in foreign demand (4.4% to 5.2%) and the supposed average oil price (USD 53 to USD 61 per Brent benchmark barrel) were both revised upward. An increase in long-term international interest rates has been reflected in a depreciation of the peso and could result in relatively tighter external financial conditions for emerging market economies, including Colombia. Average growth among Colombia’s trade partners was greater than expected in the fourth quarter of 2020. This, together with a sizable fiscal stimulus approved in the United States and the onset of a massive global vaccination campaign, largely explains the projected increase in foreign demand growth in 2021. The resilience of the goods market in the face of global crisis and an expected normalization in international trade are additional factors. These considerations and the expected continuation of a gradual reduction of mobility restrictions abroad suggest that Colombia’s trade partners could grow on average by 5.2% in 2021 and around 3.4% in 2022. The improved prospects for global economic growth have led to an increase in current and expected oil prices. Production interruptions due to a heavy winter, reduced inventories, and increased supply restrictions instituted by producing countries have also contributed to the increase. Meanwhile, market forecasts and recent Federal Reserve pronouncements suggest that the benchmark interest rate in the U.S. will remain stable for the next two years. Nevertheless, a significant increase in public spending in the country has fostered expectations for greater growth and inflation, as well as increased uncertainty over the moment in which a normalization of monetary policy might begin. This has been reflected in an increase in long-term interest rates. In this context, emerging market economies in the region, including Colombia, have registered increases in sovereign risk premiums and long-term domestic interest rates, and a depreciation of local currencies against the dollar. Recent outbreaks of COVID-19 in several of these economies; limits on vaccine supply and the slow pace of immunization campaigns in some countries; a significant increase in public debt; and tensions between the United States and China, among other factors, all add to a high level of uncertainty surrounding interest rate spreads, external financing conditions, and the future performance of risk premiums. The impact that this environment could have on the exchange rate and on domestic financing conditions represent risks to the macroeconomic and monetary policy forecasts. Domestic financial conditions continue to favor recovery in economic activity. The transmission of reductions to the policy interest rate on credit rates has been significant. The banking portfolio continues to recover amid circumstances that have affected both the supply and demand for loans, and in which some credit risks have materialized. Preferential and ordinary commercial interest rates have fallen to a similar degree as the benchmark interest rate. As is generally the case, this transmission has come at a slower pace for consumer credit rates, and has been further delayed in the case of mortgage rates. Commercial credit levels stabilized above pre-pandemic levels in March, following an increase resulting from significant liquidity requirements for businesses in the second quarter of 2020. The consumer credit portfolio continued to recover and has now surpassed February 2020 levels, though overall growth in the portfolio remains low. At the same time, portfolio projections and default indicators have increased, and credit establishment earnings have come down. Despite this, credit disbursements continue to recover and solvency indicators remain well above regulatory minimums. 1.2 Monetary policy decision In its meetings in March and April the BDBR left the benchmark interest rate unchanged at 1.75%.

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In the second quarter, annual inflation (9.67%), the technical staff’s projections and its expectations continued to increase, remaining above the target. International cost shocks, accentuated by Russia's invasion of Ukraine, have been more persistent than projected, thus contributing to higher inflation. The effects of indexation, higher than estimated excess demand, a tighter labor market, inflation expectations that continue to rise and currently exceed 3%, and the exchange rate pressures add to those described above. High core inflation measures as well as in the producer price index (PPI) across all baskets confirm a significant spread in price increases. Compared to estimates presented in April, the new forecast trajectory for headline and core inflation increased. This was partly the result of greater exchange rate pressure on prices, and a larger output gap, which is expected to remain positive for the remainder of 2022 and which is estimated to close towards yearend 2023. In addition, these trends take into account higher inflation rate indexation, more persistent above-target inflation expectations, a quickening of domestic fuel price increases due to the correction of lags versus the parity price and higher international oil price forecasts. The forecast supposes a good domestic supply of perishable foods, although it also considers that international prices of processed foods will remain high. In terms of the goods sub-basket, the end of the national health emergency implies a reversal of the value-added tax (VAT) refund applied to health and personal hygiene products, resulting in increases in the prices of these goods. Alternatively, the monetary policy adjustment process and the moderation of external shocks would help inflation and its expectations to begin to decrease over time and resume their alignment with the target. Thus, the new projection suggests that inflation could remain high for the second half of 2022, closing at 9.7%. However, it would begin to fall during 2023, closing the year at 5.7%. These forecasts are subject to significant uncertainty, especially regarding the future behavior of external cost shocks, the degree of indexation of nominal contracts and decisions made regarding the domestic price of fuels. Economic activity continues to outperform expectations, and the technical staff’s growth projections for 2022 have been revised upwards from 5% to 6.9%. The new forecasts suggest higher output levels that would continue to exceed the economy’s productive capacity for the remainder of 2022. Economic growth during the first quarter was above that estimated in April, while economic activity indicators for the second quarter suggest that the GDP could be expected to remain high, potentially above that of the first quarter. Domestic demand is expected to maintain a positive dynamic, in particular, due to the household consumption quarterly growth, as suggested by vehicle registrations, retail sales, credit card purchases and consumer loan disbursement figures. A slowdown in the machinery and equipment imports from the levels observed in March contrasts with the positive performance of sales and housing construction licenses, which indicates an investment level similar to that registered for the first three months of the year. International trade data suggests the trade deficit would be reduced as a consequence of import levels that would be lesser than those observed in the first quarter, and stable export levels. For the remainder of the year and 2023, a deceleration in consumption is expected from the high levels seen during the first half of the year, partially as a result of lower repressed demand, tighter domestic financial conditions and household available income deterioration due to increased inflation. Investment is expected to continue its slow recovery while remaining below pre-pandemic levels. The trade deficit is expected to tighten due to projected lower domestic demand dynamics, and high prices of oil and other basic goods exported by the country. Given the above, economic growth in the second quarter of 2022 would be 11.5%, and for 2022 and 2023 an annual growth of 6.9% and 1.1% is expected, respectively. Currently, and for the remainder of 2022, the output gap would be positive and greater than that estimated in April, and prices would be affected by demand pressures. These projections continue to be affected by significant uncertainty associated with global political tensions, the expected adjustment of monetary policy in developed countries, external demand behavior, changes in country risk outlook, and the future developments in domestic fiscal policy, among others. The high inflation levels and respective expectations, which exceed the target of the world's main central banks, largely explain the observed and anticipated increase in their monetary policy interest rates. This environment has tempered the growth forecast for external demand. Disruptions in value chains, rising international food and energy prices, and expansionary monetary and fiscal policies have contributed to the rise in inflation and above-target expectations seen by several of Colombia’s main trading partners. These cost and price shocks, heightened by the effects of Russia's invasion of Ukraine, have been more prevalent than expected and have taken place within a set of output and employment recovery, variables that in some countries currently equal or exceed their projected long-term levels. In response, the U.S. Federal Reserve accelerated the pace of the benchmark interest rate increase and rapidly reduced liquidity levels in the money market. Financial market actors expect this behavior to continue and, consequently, significantly increase their expectations of the average path of the Fed's benchmark interest rate. In this setting, the U.S. dollar appreciated versus the peso in the second quarter and emerging market risk measures increased, a behavior that intensified for Colombia. Given the aforementioned, for the remainder of 2022 and 2023, the Bank's technical staff increased the forecast trajectory for the Fed's interest rate and reduced the country's external demand growth forecast. The projected oil price was revised upward over the forecast horizon, specifically due to greater supply restrictions and the interruption of hydrocarbon trade between the European Union and Russia. Global geopolitical tensions, a tightening of monetary policy in developed economies, the increase in risk perception for emerging markets and the macroeconomic imbalances in the country explain the increase in the projected trajectory of the risk premium, its trend level and the neutral real interest rate1. Uncertainty about external forecasts and their consequent impact on the country's macroeconomic scenario remains high, given the unpredictable evolution of the conflict between Russia and Ukraine, geopolitical tensions, the degree of the global economic slowdown and the effect the response to recent outbreaks of the pandemic in some Asian countries may have on the world economy. This macroeconomic scenario that includes high inflation, inflation forecasts, and expectations above 3% and a positive output gap suggests the need for a contractionary monetary policy that mitigates the risk of the persistent unanchoring of inflation expectations. In contrast to the forecasts of the April report, the increase in the risk premium trend implies a higher neutral real interest rate and a greater prevailing monetary stimulus than previously estimated. For its part, domestic demand has been more dynamic, with a higher observed and expected output level that exceeds the economy’s productive capacity. The surprising accelerations in the headline and core inflation reflect stronger and more persistent external shocks, which, in combination with the strength of aggregate demand, indexation, higher inflation expectations and exchange rate pressures, explain the upward projected inflation trajectory at levels that exceed the target over the next two years. This is corroborated by the inflation expectations of economic analysts and those derived from the public debt market, which continued to climb and currently exceed 3%. All of the above increase the risk of unanchoring inflation expectations and could generate widespread indexation processes that may push inflation away from the target for longer. This new macroeconomic scenario suggests that the interest rate adjustment should continue towards a contractionary monetary policy landscape. 1.2. Monetary policy decision Banco de la República’s Board of Directors (BDBR), at its meetings in June and July 2022, decided to continue adjusting its monetary policy. At its June meeting, the BDBR decided to increase the monetary policy rate by 150 basis points (b.p.) and its July meeting by majority vote, on a 150 b.p. increase thereof at its July meeting. Consequently, the monetary policy interest rate currently stands at 9.0% . 1 The neutral real interest rate refers to the real interest rate level that is neither stimulative nor contractionary for aggregate demand and, therefore, does not generate pressures that lead to the close of the output gap. In a small, open economy like Colombia, this rate depends on the external neutral real interest rate, medium-term components of the country risk premium, and expected depreciation. Box 1: A Weekly Indicator of Economic Activity for Colombia Juan Pablo Cote Carlos Daniel Rojas Nicol Rodriguez Box 2: Common Inflationary Trends in Colombia Carlos D. Rojas-Martínez Nicolás Martínez-Cortés Franky Juliano Galeano-Ramírez Box 3: Shock Decomposition of 2021 Forecast Errors Nicolás Moreno Arias

1.1 Macroeconomic summary In September, headline inflation (11.4% annually) and the average of core inflation indicators (8.6% annually) continued on a rising trend, and higher increases than expected were recorded. Forecasts increased again, and inflation expectations remained above 3%. Inflationary surprises in the third quarter were significant and widespread, and they are the result of several shocks. On the one hand, international cost and price shocks, which have mainly affected goods and foods, continue to exert upwards pressure on national inflation. In addition to these external supply shocks, domestic supply shocks have also affected foods. On the other hand, the strong recovery of aggregate demand, especially for private consumption and for machinery and equipment, as well as a higher accumulated depreciation of the Colombian peso and its pass-through to domestic prices also explain the rise in inflation. Indexation also contributes, both through the Consumer Price Index (CPI) and through the Producer Price Index (PPI), which continues to have a significant impact on electricity prices and, to a lesser degree, on other public utilities and rent. In comparison with July’s report, the new forecast trajectory for headline and core inflation (excluding food and regulated items) is higher in the forecast horizon, mainly due to exchange rate pressures, higher excess demand, and indexation at higher inflation rates, but it maintains a trend of convergence towards the target. In the case of food, a good domestic supply of perishable foods and some moderation in international processed food prices are still expected. However, the technical staff estimates higher pressures on this group’s prices from labor costs, raw material prices, and exchange rates. In terms of the CPI for regulated items, the new forecast supposes reductions in electricity prices at the end of the year, but the effects of indexation at higher inflation rates and the expected rises in fuel prices would continue to push this CPI group. Therefore, the new projection suggests that, in December, inflation would reach 11.3% and would decrease throughout 2023 and 2024, closing the year at 7.1% and 3.5%, respectively. These forecasts have a high level of uncertainty, due especially to the future behavior of international financial conditions, external price and cost shocks, the persistence of depreciation of the Colombian peso, the pace of adjustment of domestic demand, the indexation degree of nominal contracts, and the decisions that would be made regarding domestic fuel and electricity prices. Economic activity continues to surprise on the upside, and the projection of growth for 2022 rose from 6.9% to 7.9% but lowered for 2023 from 1.1% to 0.5%. Thus, excess demand is higher than estimated in the previous report, and it would diminish in 2023. Economic growth in the second quarterwas higher than estimated in July due to stronger domestic demand, mainly because of private consumption. Economic activity indicators for the third quarter suggest that the GDP would stay at a high level, above its potential, with an annual change of 6.4%, and 0.6% higher than observed in the second quarter. Nevertheless, these numbers reflect deceleration in its quarterly and annual growth. Domestic demand would show similar behavior, with a high value, higher than that of output. This can be explained partly by the strong behavior of private consumption and investment in machinery and equipment. In the third quarter, investment in construction would have continued with mediocre performance, which would still place it at levels lower than those observed before the pandemic. The trade deficit would have widened due to high imports with a stronger trend than that for exports. It is expected that, in the forecast horizon, consumption would decrease from its current high levels, partly as a consequence of tighter domestic financial conditions, lower repressed demand, higher exchange rate pressures on imported goods prices, and the deterioration of actual income due to the rise in inflation. Investment would continue to lag behind, without reaching the levels observed before the pandemic, in a context of high financing costs and high uncertainty. A lower projected behavior in domestic demand and the high levels of prices for oil and other basic goods that the country exports would be reflected in a reduction in the trade deficit. Due to all of this, economic growth for all of 2022, 2023, and 2024 would be 7.9%, 0.5%, and 1.3%, respectively. Expected excess demand (measured via the output gap) is estimated to be higher than contemplated in the previous report; it would diminish in 2023 and could turn negative in 2024. These estimates remain subject to a high degree of uncertainty related to global political tension, a rise in international interest rates, and the effects of this rise on demand and financial conditions abroad. In the domestic context, the evolution of fiscal policy as well as future measures regarding economic policy and their possible effects on macroeconomic imbalances in the country, among others, are factors that generate uncertainty and affect risk premia, the exchange rate, investment, and the country’s economic activity. Interest rates at several of the world’s main central banks continue to rise, some at a pace higher than expected by the market. This is in response to the high levels of inflation and their inflation expectations, which continue to exceed the targets. Thus, global growth projections are still being moderated, risk premia have risen, and the dollar continues to gain strength against other main currencies. International pressures on global inflation have heightened. In the United States, core inflation has not receded, pressured by the behavior of the CPI for services and a tight labor market. Consequently, the U.S. Federal Reserve continued to increase the policy interest rate at a strong pace. This rate is expected to now reach higher levels than projected in the previous quarter. Other developed and emerging economies have also increased their policy interest rates. Thus, international financial conditions have tightened significantly, which reflects in a widespread strengthening of the dollar, increases in worldwide risk premia, and the devaluation of risky assets. Recently, these effects have been stronger in Colombia than in the majority of its peers in the region. Considering all of the aforementioned, the technical staff of the bank increased its assumption regarding the U.S. Federal Reserve’s interest rate, reduced the country’s external demand growth forecast, and raised the projected trajectory for the risk premium. The latter remains elevated at higher levels than its historical average, within a context of high local uncertainty and of extensive financing needs from the foreign sector and the public sector. All of this results in higher inflationary pressures associated to the depreciation of the Colombian peso. The uncertainty regarding external forecasts and its impact on the country remain elevated, given the unforeseeable evolution of the conflict between Russia and Ukraine, of geopolitical tensions, and of the tightening of external financial conditions, among others. A macroeconomic context of high inflation, inflation expectations and forecasts above 3%, and a positive output gap suggests the need for contractionary monetary policy, compatible with the macroeconomic adjustment necessary to eliminate excess demand, mitigate the risk of unanchoring in inflation expectations, and guarantee convergence of inflation at the target. In comparison with the July report forecasts, domestic demand has been more dynamic, with a higher observed output level that surpasses the economy’s productive capacity. Headline and core inflation have registered surprising rises, associated with the effects of domestic and external price shocks that were more persistent than anticipated, with excess demand and indexation processes in some CPI groups. The country’s risk premium and the observed and expected international interest rates increased. As a consequence of this, inflationary pressures from the exchange rate rose, and in this report, the probability of the neutral real interest rate being higher than estimated increased. In general, inflation expectations for all terms and the bank’s technical staff inflation forecast for 2023 increased again and continue to stray from 3%. All of the aforementioned elevated the risk of unanchoring inflation expectations and could heighten widespread indexation processes that push inflation away from the target for a longer time. In this context, it is necessary to consolidate a contractionary monetary policy that tends towards convergence of inflation at the target in the forecast horizon and towards the reduction of excess demand in order to guarantee a sustainable output level trajectory. 1.2 Monetary policy decision In its September and October of 2022 meetings, Banco de la República’s Board of Directors (BDBR) decided to continue adjusting its monetary policy. In September, the BDBR decided by a majority vote to raise the monetary policy interest rate by 100 basis points (bps), and in its October meeting, unanimously, by 100bps. Therefore, the rate is at 11.0%. Boxes 1 Food inflation: a comparison with other countries