Academic literature on the topic 'Subclinical atherosclerosi'

Recently the research has been focused on the earlier stages of the atherosclerotic process, i.e. subclinical atherosclerosis. Endothelial dysfunction is a suitable marker of subclinical atherosclerosis. In routine clinical practice, ultrasonography is the most useful and accessible non-invasive method for diagnosis of subclinical atherosclerosis. Carotid intimai media thickness (IMT) was shown to be predictive for the risk of cardiovascular events. Furthermore, vascular stiffness can be a helpful marker for assessment of the vascular wall state and blood flow. Calcium antagonists (CA) seem to be promising for the prevention of subclinical atherosclerosis progression, and amlodipine has the priority due to the metabolic neutralilty, vasodilation effect and favourable effects on renal hemodynamics. The data on IMT assessement showed that amlodipine slows down the development of atherosclerotic lesions in hypertensive patients.

Сердечно-сосудистые заболевания остаются ведущей причиной заболеваемости и смертности во всем мире и в системе здравоохранения обуславливают самую высокую долю затрат. Патоморфологической основой ишемической болезни сердца в подавляющем большинстве клинических ситуаций является атеросклероз коронарных артерий. В последнее время множество исследований посвящено изучению ранней стадии атеросклероза – субклинического атеросклероза. Дестабилизация гемодинамически незначимых, бессимптомных атеросклеротических бляшек может привести к развитию инфаркта миокарда. В статье обсуждается распространенность, клиническая значимость необструктивного атеросклероза коронарных артерий. Отдельное внимание уделено шкалам стратификации сердечно-сосудистого риска. Обозначены современные методы диагностики коронарного атеросклероза, методы визуализации «нестабильных» атеросклеротических бляшек. В реальной клинической практике оценить «нестабильность» атеросклеротической бляшки не представляется возможным, поэтому сам факт наличия субклинического атеросклероза коронарных артерий позволяет отнести пациента к категории высокого и очень высокого риска. Cardiovascular diseases remain the leading cause of mortality and morbidity worldwide and represent the highest proportion of costs in healthcare systems. In the vast majority of cases, the pathomorphological basis of coronary heart disease is coronary artery atherosclerosis. Many of the recent research have been devoted to the study of the early stage of atherosclerosis – subclinical atherosclerosis. Destabilization of hemodynamically insignificant, asymptomatic atherosclerotic plaques can lead to the development of myocardial infarction. The article discusses the prevalence and clinical significance of non- obstructive atherosclerosis of the coronary arteries. Special attention is devoted to the scales of cardiovascular risk stratification. Modern methods of coronary atherosclerosis diagnosis, methods of visualization of unstable atherosclerotic plaques are outlined. Considering that it is impossible to assess the instability of atherosclerotic plaque in real clinical practice, the presence of subclinical coronary atherosclerosis itself allows the patient to be classified as high and very high risk.

Subclinical atherosclerosis is an initial, latent stage of chronic progressing arterial inflammation. Destabilisation of asymptomatic, hemodynamically non-significant atherosclerotic plaques (AP) could lead to myocardial infarction, stroke, or sudden death. Since the assessment of AP stability is problematic in real-world clinical settings, the risk stratification should, at least, account for the presence of subclinical atherosclerosis. In 600 ambulatory patients from the Moscow City Western Administrative Okrug who had low and moderate SCORE-assessed cardiovascular risk levels, the prevalence of AP, based on the duplex carotid ultrasound results, was 59% (n=358). Presently, no standard guidelines exist on cardiovascular risk stratification which would include the assessment of subclinical atherosclerosis, despite the importance of the latter as a prognostic factor. Large clinical studies on prognosis in patients with subclinical atherosclerosis will clarify the role of this parameter as an independent cardiovascular risk factor and facilitate the development of respective clinical recommendations.

Background: We aimed to investigate the association of toenail onychomycosis with subclinical atherosclerosis in patients with diabetes mellitus. Patients and methods: Consecutive diabetic patients who were seen at our outpatient clinic were enrolled. The carotid intima-media thickness (CIMT) was assessed and toenail onychomycosis was diagnosed with microscopic evaluation. Results: We investigated 127 patients with diabetes melltus type 2. Overall, the prevalence of toenail onychomycosis was 37.8 % (48 of 127). Of the 127 patients, 60 (47.2 %) had subclinical atherosclerosis (CIMT ≥ 1 mm). Prevalence of male gender (43.3 % vs. 22.4 %, p = 0.012) and onychomycosis (53.3 % vs. 23.9 %, p = 0.001) was significantly higher in patients with subclinical atherosclerosis. Among biochemical parameters, low-density lipoprotein (122 ± 38 mg/dL vs. 108 ± 36 mg/dL, p = 0.039) and glycosylated hemoglobin levels (median 8.4 %, IQR: 2.1 % vs. median 7.5 %, IQR: 1.6 %, p = 0.002) were significantly higher in patients with subclinical atherosclerosis. Study groups were similar with respect to all other demographic, clinical, and laboratory parameters. After adjustment for all potential confounders, the presence of onychomycosis was independently associated with subclinical atherosclerosis (OR 2.77, 95 % CI 1.16 to 6.30) in multivariate logistic regression analysis. Conclusions: Presence of onychomycosis in patients with diabetes is associated with subclinical atherosclerosis. Onychomycosis may be a marker of atherosclerotic arterial involvement.

Background.Cardiovascular disease (CVD) remains a significant problem in Chronic Kidney Disease (CKD). Subclinical atherosclerosis identified by noninvasive methods could improve CVD risk prediction in CKD but these methods are often unavailable. We therefore systematically reviewed whether circulating levels of Matrix Metalloproteinases (MMPs) and tissue inhibitors (TIMPs) are associated with subclinical atherosclerosis in CKD, as this would support their use as biomarkers or pharmacologic targets.Methods.All major electronic databases were systematically searched from inception until May 2015 using appropriate terms. Studies involving CKD patients with data on circulating MMPs levels and atherosclerosis were considered and subjected to quality assessment.Results.Overall, 16 studies were identified for qualitative synthesis and 9 studies were included in quantitative synthesis. MMP-2 and TIMP-1 were most frequently studied while most studies assessed carotid Intima-Media Thickness (cIMT) as a measure of subclinical atherosclerosis. Only MMP-2 demonstrated a consistent positive association with cIMT. Considerable variability in cIMT measurement methodology and poor plaque assessment was found.Conclusions.Although MMPs demonstrate great potential as biomarkers of subclinical atherosclerosis, they are understudied in CKD and not enough data existed for meta-analysis. Larger studies involving several MMPs, with more homogenized approaches in determining the atherosclerotic burden in CKD, are needed.

Background: Current data on the possible involvement of aging neutrophils in atherogenesis are limited. This study aimed to research the diagnostic value of aging neutrophils in their relation to subclinical atherosclerosis in statin-naïve patients without established atherosclerotic cardiovascular diseases (ASCVD). Methods: The study was carried out on 151 statin-naïve patients aged 40–64 years old without ASCVD. All patients underwent duplex scanning of the carotid arteries, lower limb arteries and abdominal aorta. Phenotyping and differentiation of neutrophil subpopulations were performed through flow cytometry (Navios 6/2, Beckman Coulter, USA). Results: The number of CD62LloCXCR4hi-neutrophils is known to be significantly higher in patients with subclinical atherosclerosis compared with patients without atherosclerosis (p = 0.006). An increase in the number of CD62LloCXCR4hi-neutrophils above cut-off values makes it possible to predict atherosclerosis in at least one vascular bed with sensitivity of 35.4–50.5% and specificity of 80.0–92.1%, in two vascular beds with sensitivity of 44.7–84.4% and specificity of 80.8–33.3%. Conclusion: In statin-naïve patients 40–64 years old without established ASCVD with subclinical atherosclerosis, there is an increase in circulating CD62LloCXCR4hi-neutrophils. It was also concluded that the increase in the number of circulating CD62LloCXCR4hi-neutrophils demonstrated moderate diagnostic efficiency (AUC 0.617–0.656) in relation to the detection of subclinical atherosclerosis, including polyvascular atherosclerosis.

Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and metabolic syndrome. Although the precise pathogenetic links between psoriasis and atherosclerosis warrants further investigation, it is believed that chronic systemic inflammation along with the T helper (Th)-1 and Th17 polarization are associated with endothelial dysfunction and subsequent acceleration of atherosclerosis. Considering the above, several studies have evaluated if optimal control of the inflammation in psoriasis by inhibiting interleukins targeting the Interleukin (IL)-23/Th17 axis could subsequently reduce the atherosclerotic process during anti-psoriatic treatment by using a variety of surrogate markers of subclinical atherosclerosis. This systematic review summarizes current knowledge on the pathogenetic mechanisms and diagnostic evaluation of atherosclerosis in the context of psoriasis and provides a systematic review of the literature on the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis.

Cardiovascular risk (CVR) stratification plays an important role in the primary prevention of atherosclerosis and associated disorders. The standard scales for CVR assessment (Framingham scale, SCORE scale, etc.) are focused on a limited number of traditional risk factors (RFs) and, therefore, neither produce precise individual risk estimates, nor increase the effectiveness of preventive interventions. One of the methods for CVR assessment optimisation is the diagnostics of subclinical atherosclerosis, based on the direct visualisation of preclinical atherosclerotic changes in arterial wall. Extracranial carotid artery (CA) ultrasound and assessment of the intima-media thickness (IMT) index or atherosclerotic plaque volume (PV) is an important method of the preclinical atherosclerosis diagnostics. The review discusses pathogenetic mechanisms of IMT increase, the standards of ultrasound IMT assessment and its interpretation, and the role of the information obtained for optimization of the CVR evaluation.

In this review of literature present duplex scanning technology as modern noninvasive information technique of subclinical carotid atherosclerosis verification. The article gives assessment and description of intima-media complex thicknesses and atherosclerotic plaques in patients risk stratification within the scope of primary cardiovascular prophylaxis.

Background: Atherosclerosis is emerging as an important complication of rheumatoid arthritis (RA), with coronary artery disease being projected as the major cause of mortality in these patients.This study was undertaken to evaluate the presence of subclinical atherosclerosis and to identify the risk factors of atherosclerosis in patients with RA. Patients and methods: All consecutive in- and out-patients of rheumatoid arthritis (n = 100) irrespective of the disease duration were included in the study. A group of 100 age and sex matched controls were also studied. Increased carotid intima media thickness (beyond the 75th percentile for age and sex), presence of plaques, ankle brachial pressure index and QT dispersion were deemed as non-invasive measures of atherosclerotic burden. Results: Fifty patients (50.0 %) with RA had evidence of subclinical atherosclerosis as compared to the control group (n = 11, 11 %); plaques were observed in 26 patients. Eighteen (36 %) of these developed this evidence within 1 - 5 years of disease onset. Low HDL levels among the conventional risk factors and advanced patient age, longer disease duration, greater number of involved joint areas, steroid use and indices of inflammation in particular in RA, were associated with subclinical atherosclerosis. Sustained inflammation was observed throughout the sub-group with atherosclerosis irrespective of the disease duration. Conclusions: RA is a pro-atherogenic state with the process of atherosclerosis initiated in the early stage of the disease. Besides the traditional risk factors, sustained inflammation contributes to atherogenesis.

Contesto e scopo: La proproteina convertasi subtilisina/kexina di tipo 9 (PCSK9), uno dei principali regolatori del metabolismo del recettore delle LDL, è stata associata allo sviluppo di aterosclerosi. Diversi studi hanno confermato tale associazione attraverso vie lipidiche e non lipidiche. Tuttavia, le relazioni dirette tra PCSK9 circolante e marcatori di aterosclerosi subclinica e clinica sono ancora da chiarire. Pertanto, abbiamo valutato le relazioni tra i livelli plasmatici di PCSK9 ed alcuni indici di aterosclerosi subclinica (marcatori di imaging) e clinica (eventi vascolari; EV). Un altro obiettivo è stato l'identificazione dei determinanti indipendenti di PCSK9, con particolare attenzione ai lipidi e ai biomarcatori infiammatori. Infine, abbiamo anche valutato la relazione tra alcuni marcatori di imaging e quattro SNPs del gene PCSK9, noti per essere associati alla presenza di bassi livelli di colesterolo LDL. Per validare i risultati ottenuti in quest’ultima parte, le analisi genetiche sono state replicate in una coorte indipendente reclutata nel Regno Unito (UK). Metodi: Lo studio è stato realizzato sfruttando le banche dati, biobanche e la banca di immagini dello studio IMPROVE. 3,703 soggetti europei (54-79 anni; 48% uomini), privi di EV al basale e definiti ad alto rischio per la presenza di almeno tre fattori di rischio vascolare, sono stati reclutati e seguiti per 36 mesi. PCSK9 è stata misurata tramite ELISA e trasformata in logaritmo prima delle analisi. I marcatori di imaging convenzionali [spessore medio-intimale carotideo (cIMT, dall’inglese intima-media thickness) e dimensione della placca carotidea] ed emergenti [cambiamento di cIMT nel tempo, ecolucenza dello spessore del complesso medio intimale della carotide comune misurato in zone libere da placca (PF CC-IMTmean), ecolucenza della placca più grande rilevata in tutto l'albero carotideo e punteggio di calcio carotideo (cCS, dall’inglese carotid calcium score)] sono stati misurati su scansioni ultrasonografiche conservate nella banca di immagini. In particolare, l'ecolucenza è stata misurata in termini di mediana della scala dei grigi (GSM, dall’inglese grey scale median) della distribuzione dei pixel di una specifica regione d’interesse, mentre il cCS è stato calcolato come somma delle lunghezze dei coni d’ombra acustici generati dal calcio all'interno delle placche carotidee. I lipidi sono stati misurati con metodi enzimatici (ad eccezione del colesterolo LDL che è stato calcolato con la formula di Friedewald). Tra i marcatori infiammatori, la proteina C reattiva ad alta sensibilità (hs-PCR) è stata misurata con la turbidimetria, mentre il conteggio dei globuli bianchi (WBC, dall’inglese white blood cells) e la formula leucocitaria sono stati misurati localmente. Tutti i soggetti dello studio IMPROVE e della coorte UK (n=22,179; 48 % uomini) sono stati genotipizzati. Risultati: Nell'analisi univariata, PCSK9 correlava positivamente con colesterolo totale, LDL e HDL e con trigliceridi e basofili (tutte le p <0.0001), mentre correlava negativamente con neutrofili ed eosinofili (entrambe le p=0.04). Le correlazioni positive osservate con hs-PCR e con il conteggio dei WBC erano solo vicine alla significatività statistica (p=0.060 e 0.064, rispettivamente). Le terapie con fibrati o statine (positivamente; entrambe le p <0.0001), così come sesso maschile e storia familiare di diabete (negativamente; entrambe le p <0.05) erano i predittori indipendenti più forti dei livelli plasmatici di PCSK9. Nell'analisi non aggiustata, si osservava una correlazione negativa tra PCSK9 e variabili basali di cIMT (IMTmean, IMTmax, IMTmean-max, e PF CC-IMTmean), una correlazione negativa tra PCSK9 e la variazione di cIMT nel tempo (Fastest-IMTmax-progr) e cCS (tutte le p ≤0.01), mentre si osservava un trend positivo tra PCSK9 e GSM sia del PF CC-IMTmean che della placca carotidea (entrambe le p ≤0.0001). Il cCS (positivamente) e il GSM del PF CC-IMTmean (positivamente) erano associati significativamente (o vicini alla significatività) a PCSK9 in diversi modelli multivariati (tutte le p ≤0.064). Tutte le correlazioni osservate all’analisi univariata tra PCSK9 e le variabili basali di cIMT, Fastest-IMTmax-progr e GSM della placca carotidea perdevano la significatività statistica dopo aggiustamento delle stesse per età, sesso, latitudine ed altri potenziali confondenti. Durante il follow-up [mediana (intervallo interquartile): 3.01 (2.98; 3.12) anni], sono stati registrati 215 EV: 125 coronarici, 73 cerebrali e 17 EV periferici. Tra questi, 37 erano eventi hard (infarto miocardico, morte improvvisa ed ictus). Nell'analisi non aggiustata, PCSK9 era associata positivamente ad eventi combinati e coronarici (entrambe le p <0.01), ma non ad eventi cerebrovascolari. Anche in questo caso, tuttavia, tutte le associazioni osservate perdevano la significatività statistica dopo aggiustamento delle analisi per età, sesso e stratificazione per latitudine. La mancanza di associazione con EV era confermata anche nel modello aggiustato per tutti i fattori confondenti considerati e nelle analisi focalizzate sugli eventi hard. Per quanto riguarda il ruolo delle varianti genetiche, nessuno dei quattro SNPs considerati correlava con cIMT (IMTmean, IMTmax, IMTmean-max) quando l'analisi era effettuata nei soggetti reclutati nello studio IMPROVE. La variante rs11591147, invece, correlava negativamente con l’IMTmax misurato nella popolazione UK (p=0.002). Combinando le quattro varianti genetiche in uno score, la relazione con cIMT era non significativa nello studio IMPROVE, mentre era negativa e significativa nella popolazione UK (tutte le p <0.01). Conclusioni: I livelli plasmatici di PCSK9 non sono associati a EV. Per quanto riguarda i marcatori dell'aterosclerosi subclinica, i livelli plasmatici di PCSK9 non sono associati né alla dimensione della lesione, né all'ecolucenza della placca carotidea, ma sono associati all'ecolucenza dello spessore della parete carotidea e al carotid calcium score. Ulteriori studi sono pertanto necessari per comprendere meglio il ruolo di tale proproteina nell'ecolucenza dello spessore della parete carotidea e nel carotid calcium score. La terapia con fibrati o statine, così come il sesso maschile e la storia familiare di diabete sono i predittori indipendenti più forti di PCSK9 circolante. È stata inoltre confermata l'associazione, precedentemente osservata, tra PCSK9 circolante e alcuni marcatori lipidici ed infiammatori. La relazione tra i livelli plasmatici di PCSK9 ed altri marcatori infiammatori (neutrofili, basofili ed eosinofili) merita ulteriori indagini, così come merita ulteriori indagini l’associazione tra le quattro varianti genetiche di PCSK9 selezionate e il cIMT nella coorte britannica, in quanto lascia intravvedere un possibile ruolo di SNPs o polimorfismi genici di PCSK9 nell’aterosclerosi e nelle strategie della sua prevenzione.
Background and purpose: Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the main regulators of LDL receptor metabolism, has been associated with atherosclerosis development. Several studies have confirmed such association through both lipid and non-lipid pathways. However, the direct relationships between circulating PCSK9 and markers of subclinical and clinical atherosclerosis are still matter of debate. Therefore, we investigated the relationships between plasma PCSK9 levels and some indexes of subclinical (imaging markers) and clinical (vascular events; VEs) atherosclerosis. Another objective was the identification of the independent determinants of PCSK9, with particular attention to lipids and inflammatory biomarkers. Finally, we also assessed the relationship between some imaging markers and four SNPs of the PCSK9 gene, known to be associated with the presence of low levels of LDL-cholesterol. In order to validate the results obtained in this last part, the genetic analyses were replicated in an independent cohort recruited in the United Kingdom (UK). Methods: The study was carried out taking advantage of databases, biobanks and imaging-bank of the IMPROVE study. 3,703 European subjects (54-79 years; 48% men), free of VEs at baseline and defined at high risk for the presence of at least three vascular risk factors, were recruited and followed-up for 36 months. PCSK9 was measured by ELISA and log-transformed prior to analyses. Conventional imaging markers [carotid intima-media thickness (cIMT) and carotid plaque-size], and emerging imaging markers [cIMT change over time, echolucency of the intima-media thickess of common carotid measured in plaque free areas (PF CC-IMTmean), echolucency of the biggest plaque detected in the whole carotid tree, and carotid calcium score (cCS)] were measured on ultrasonographic scans stored in the imaging-bank. In particular, echolucency was measured in terms of grey scale median (GSM) of pixels distribution of a specific region of interest, whereas cCS was calculated as sum of lengths of acoustic shadow cones generated by calcium within carotid plaques. Lipids were measured with enzymatic methods (except for LDL-cholesterol, which was calculated by Friedewald's formula). Among inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) was measured by turbidimetry, whereas white blood cells (WBC) count and the leukocyte formula had already been measured locally. All the IMPROVE study and UK (n=22,179; 48% men) subjects have been genotyped. Results: In the univariate analysis, PCSK9 was positively correlated with total, LDL-, and HDL-cholesterol, and with triglycerides and basophils (all p <0.0001), whereas was negatively correlated with neutrophils and eosinophils (both p=0.04). The positive correlations observed with hs-CRP and WBC count were just close to the statistical significance (p=0.060 and 0.064, respectively). Fibrates or statins therapies (positively; both p <0.0001), as well as male sex and family history of diabetes (negatively; both p <0.05) were the strongest independent predictors of plasma PCSK9 levels. In the unadjusted analysis, a negative correlation was observed between PCSK9 levels and basal cIMT variables (i.e. carotid IMTmean, IMTmax, IMTmean-max, and PF CC-IMTmean), a negative correlation between PCSK9 and cIMT change over time (Fastest-IMTmax-progr) and cCS (all p ≤0.01), whereas a positive trend was observed between PCSK9 and GSM of both PF CC-IMTmean and carotid plaque (both p ≤0.0001). The cCS (positively) and the GSM of PF CC-IMTmean (positively) were significantly (or almost significantly) associated with PCSK9 in several multivariate models (all p ≤0.064). All correlations observed in the univariate analysis between PCSK9 and basal cIMT variables, Fastest-IMTmax-progr and GSM of carotid plaque lost the statistical significance after adjustment for age, sex, latitude, and other potential confounders. During the follow-up [median (interquartile range): 3.01 (2.98; 3.12) years], 215 VEs were recorded: 125 coronary, 73 cerebral and 17 peripheral VEs. Among these, 37 were hard events (i.e. myocardial infarction, sudden death and stroke). In the unadjusted analysis, PCSK9 was positively associated with combined and coronary events (both p <0.01), but not with cerebrovascular events. Also in this case, however, all the associations observed lost the statistical significance after adjustment of the analyses for age, sex, and stratification for latitude. The lack of association with VEs was confirmed also in the model adjusted for all confounding factors considered, and in the analyses focused on hard events. With regard to the role of genetic variants, none of the four SNPs considered was correlated with cIMT (i.e. IMTmean, IMTmax, IMTmean-max) when the analysis was performed in the subjects recruited in the IMPROVE study. The rs11591147 variant, by contrast, was negatively correlated with IMTmax measured in the UK population (p=0.002). By combining the four genetic variants in a score, the relationship with cIMT was not significant in the IMPROVE study, whereas was negative and significant in the UK population (all p <0.01). Conclusions: Plasma PCSK9 levels are not associated with VEs. Regarding markers of subclinical atherosclerosis, PCSK9 levels are associated neither with lesion size, nor with carotid plaque echolucency, but are associated with echolucency of carotid wall thickness and with carotid calcium score. Therefore, further studies are needed to better understand the role of such circulating proprotein in carotid wall thickness echolucency and in carotid calcium score. Fibrates or statins therapies, as well as male sex and family history of diabetes are the strongest independent predictors of PCSK9 levels. The associations, previously observed, between circulating PCSK9 and some lipid and inflammatory markers have been confirmed. The relationship between plasma levels of PCSK9 and other inflammatory markers (neutrophils, basophils and eosinophils) deserves further investigation, as does the association between the four selected PCSK9 variants and cIMT in the UK cohort, as it suggests a possible role of PCSK9 SNPs or gene polymorphisms in atherosclerosis and in its preventive strategies.

Background: Cardiovascular health disparities across subpopulations and geographies have been well-documented in urban areas. Evidence suggests that racial minorities and low-socioeconomic groups have high risks of developing cardiovascular diseases (CVD). Residents of the Appalachia also exhibit high rates of CVD, but little is known about the relationships between cardiovascular risk factors, spatial disadvantage, and cardiovascular health outcomes in this region. Thus, this study aimed to examine the independent association between neighborhood factors and subclinical atherosclerosis in an asymptomatic population from central Appalachia. Methods: Community-dwelling asymptomatic individuals (n=210) were screened for Coronary Artery Calcium (CAC), a subclinical marker for coronary atherosclerosis, from January 2010 to January 2014. Based on the standard Agatston Scale, participants were grouped into 4 CAC scores: zero (CAC = 0), mild (CAC = 1-99), moderate (CAC = 100-399) and severe (CAC ≥ 400) to determine the severity of coronary artery disease (CAD). Demographic information (e.g., age, gender, race, and marital status), cardiovascular risk factors (e.g., hypertension, hypercholesterolemia, obesity, smoking, and family history of CAD), and neighborhood level characteristics (racial and socioeconomic characteristics of the population) were used in ordinal logistic regression analyses performed in Stata 14.1. Results: Of the 210 participants, over three-fourths (79%) had a CAC score greater than 1. While 67% of the participants were hypertensive, 80% had hypercholesterolemia, 75% were overweight or obese, 52% had a history of smoking, and 55% had a family history of CAD. There were significant differences in the socioeconomic environment of these residents. Specifically, zip-code median household income was higher for individuals with zero CAC score. Additionally, the zip-code household poverty percentage was higher for those with CAC scores ≥ 1. Although all the neighborhood factors increased the odds of having higher CAC score, none of them were statistically significant. Conclusion: The positive, albeit statistically non-significant, association of adverse neighborhood factors with higher CAC scores suggests the need for larger studies for further understanding of this association. Finally, achieving the Healthy People 2020 goal of reducing or eliminating disparities requires risk factor screening and control in high prevalent areas such as central Appalachia, and understanding the neighborhood level dynamics for CVD.

La malaltia cardiovascular és la primera causa de morbiditat i mortalitat mundial. Els individus amb diabetis i malaltia renal crònica (MRC) presenten un major risc d’esdeveniments cardiovasculars (ECV) respecte a la població general. En la diabetis, l’increment de el risc cardiovascular és heterogeni i s’ha relacionat amb el grau d’afectació renal. D’altra banda, els algoritmes tradicionals per calcular el risc cardiovascular no traslladen amb suficient precisió el risc futur de ECV. L’avaluació de l’aterosclerosi subclínica (AS) mitjançant ecografia multiterritorial representa una eina vàlida per refinar el risc cardiovascular. El propòsit d’aquesta tesi va ser analitzar mitjançant ecografia multiterritorial la prevalença, distribució i progressió de AS, així com factors de risc associats, en una àmplia cohort de pacients, sense malaltia cardiovascular, amb MRC i amb i sense diabetis. Posteriorment, es va avaluar el valor pronòstic de l’AS per determinar la incidència d’ECV en aquesta població d’alt risc. Inicialment, es van analitzar les dades dels subjectes amb MRC, amb diabetis i sense diabetis, de la cohort de l’estudi NEFRONA reclutats a l’inici de l’estudi i que van assistir a la visita de control als 24 mesos. Després de realitzar un estudi ultrasonogràfic carotidi i femoral tant en la visita inicial com en la de seguiment, es va avaluar la correlació de factors de risc associats amb prevalença i progressió de placa mitjançant anàlisi multivariables. Així mateix, es va realitzar una altra anàlisi amb tots els subjectes de l’estudi, amb i sense diabetis, reclutats inicialment i als quals se’ls va seguir durant 48 mesos. Durant el període de seguiment es van registrar els ECV incidents. Es van utilitzar anàlisis bivariades i anàlisi de model de riscos competitius de Fine-Grey per a l’estudi estadístic. L’índex C es va estimar per als models de risc resultants amb més potència. Com a resultats, es va observar que la proporció d’individus amb placa basal va ser més gran entre els subjectes amb diabetis. Els subjectes amb diabetis també van presentar amb més freqüència l’afectació amb placa de més de dos territoris vasculars. També es va observar més progressió de placa entre els individus amb diabetis. Després de realitzar l’anàlisi multivariable, es va demostrar que la presència de placa basal s’associava amb l’edat, el gènere masculí, l’hàbit tabàquic i la diàlisi en els subjectes sense diabetis mentre que, en els subjectes amb diabetis, la presència de placa basal es associar tan sols a l’edat i al gènere masculí. La progressió de placa es va associar a l’edat, a el nombre de territoris amb placa basal, a l’hàbit tabàquic i a la diàlisi en els dos grups. Es van registrar un total de 107 ECV entre els subjectes sense diabetis (19.58 per 1000 anys-persona) i 96 entre els subjectes amb diabetis (44.44 per 1000 anys-persona). El model que millor va predir futurs ECV en individus sense diabetis contenia les variables: edat, 25-OH vitamina D i nombre de territoris amb placa basal. Entre els participants amb diabetis el model més robust en predir ECV incidents contenia tan sols la variable nombre de territoris amb placa basal. Per a tots dos models, l’índex estadístic C, estimat als 24 i als 48 mesos, va ser superior a 0.70. La AS és més prevalent, comporta major càrrega i és més progressiva en individus amb MRC i diabetis. En aquests subjectes, la diabetis supera altres factors de risc descrits. Així mateix, la càrrega d’AS és el predictor més potent de futurs ECV en individus amb diabetis i MRC. La detecció precoç de càrrega AS mitjançant ultrasonografia multiterritorial podria millorar la predicció de ECV en aquesta població.
La enfermedad cardiovascular es la primera causa de morbilidad y mortalidad mundial. Los individuos con diabetes y enfermedad renal crónica (ERC) presentan un mayor riesgo de eventos cardiovasculares (ECV) con respecto a la población general. En la diabetes, el incremento del riesgo cardiovascular es heterogéneo y se ha relacionado con el grado de afectación renal. Por otra parte, los algoritmos tradicionales para calcular el riesgo cardiovascular no trasladan con suficiente precisión el riesgo futuro de ECV. La evaluación de la aterosclerosis subclínica (AS) mediante ecografía multiterritorial representa una herramienta válida para refinar el riesgo cardiovascular. El propósito de esta tesis fue analizar mediante ecografía multiterritorial la prevalencia, distribución y progresión de AS, así como factores de riesgo asociados, en una amplia cohorte de pacientes, sin enfermedad cardiovascular, con ERC y con y sin diabetes. Posteriormente, se evaluó el valor pronóstico de la AS para determinar la incidencia de ECV en esta población de alto riesgo. Inicialmente, se analizaron los datos de los sujetos con ERC, con diabetes y sin diabetes, de la cohorte del estudio NEFRONA reclutados al inicio del estudio y que asistieron a la visita de control a los 24 meses. Tras realizar un estudio ultrasonográfico carotídeo y femoral tanto en la visita inicial como en la de seguimiento, se evaluó la correlación de factores de riesgo asociados con prevalencia y progresión de placa mediante análisis multivariables. Asimismo, se realizó otro análisis con todos los sujetos del NEFRONA, con y sin diabetes, reclutados inicialmente y a los que se les siguió durante 48 meses. Durante el periodo de seguimiento se registraron los ECV incidentes. Se utilizaron análisis bivariados y análisis de modelo de riesgos competitivos de Fine-Grey para el estudio estadístico. El índice C se estimó para los modelos de riesgo resultantes con mayor potencia. Como resultados, se observó que la proporción de individuos con placa basal fue mayor entre los sujetos con diabetes. Los sujetos con diabetes presentaron con mayor frecuencia la afectación con placa de más de dos territorios vasculares. También se observó una mayor progresión de placa en los individuos con diabetes. Tras realizar el análisis multivariable, se demostró que la presencia de placa basal se asociaba con la edad, el género masculino, el hábito tabáquico y la diálisis en los sujetos sin diabetes mientras que, en los sujetos con diabetes, la presencia de placa basal se asoció tan sólo a la edad y al género masculino. La progresión de placa se asoció a la edad, al número de territorios con placa basal, al hábito tabáquico y a la diálisis en ambos grupos. Se registraron 107 ECV entre los sujetos sin diabetes (19.58 por 1000 años-persona) y 96 entre los sujetos con diabetes (44.44 por 1000 años-persona). El modelo que mejor predijo futuros ECV en individuos sin diabetes contenía las variables: edad, 25-OH vitamina D y número de territorios con placa basal. Entre los participantes con diabetes el modelo más robusto en predecir ECV incidentes contenía tan sólo la variable ‘número de territorios con placa basal’. Para ambos modelos, el índice estadístico C, estimado a los 24 y a los 48 meses, fue superior a 0.70. La AS es más prevalente, conlleva mayor carga y es más progresiva en individuos con ERC y diabetes. En estos sujetos, la diabetes supera otros factores de riesgo descritos. Así mismo, la carga de AS es el predictor más potente de futuros ECV en individuos con diabetes y ERC. La detección precoz de carga AS mediante ultrasonografía multiterritorial podría mejorar la predicción de ECV en esta población.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Individuals with diabetes and chronic kidney disease (CKD) have remarkably high rates of CVD risk. Moreover, incremental cardiovascular risk in diabetes is heterogeneous and has been often related to concomitant CKD. Typically used risk equations based on traditional cardiovascular risk factors fail to accurately predict cardiovascular risk not only in the general population but also in these subsets of the population. Multi-territorial ultrasonography to assess subclinical atherosclerosis (SA) has emerged as a valid tool to refine cardiovascular risk assessment beyond traditional risk factors. The purpose of this thesis was to analyse the prevalence, distribution, and progression of SA, as well as the associated cardiovascular risk factors in a large cohort of CKD subjects with and without diabetes, free from CVD, using multi-territorial ultrasonography. Subsequently, we further evaluated the prognostic value of SA in determining the incidence of first cardiovascular events (CVE) in this high-risk population. First, we included the data from CKD subjects with and without diabetes and free from previous CVE from the NEFRONA cohort, that were recruited at baseline, and that attended a follow-up visit 24 months later. Participants underwent carotid and femoral ultrasound examinations at baseline and at 24-month follow-up. Risk factors associated with the prevalence and progression of SA were evaluated using multivariate model analyses. In the second hand, we also conducted another analysis including data from the NEFRONA cohort subjects with and without diabetes that were recruited initially and were followed-up for 48 months. During the follow-up period, all CVE were registered. Bivariate analysis and Fine-Gray competing risk models were used to perform the statistical analysis. Concordance Index (C-statistics) was estimated for the strongest resulting risk models. We found that at baseline, the proportion of subjects with plaque at any of the examined territories was higher among diabetic individuals. Diabetic subjects more frequently had more than two vascular territories with plaque. During a 24-month follow-up period, plaque progression occurred in 72.2% individuals with diabetes whereas, among individuals without diabetes, plaque progression occurred in 55.8%. Multivariable analysis indicated that plaque at baseline was significantly associated with age, male gender, smoking, and dialysis in the non-diabetic subjects, while only age and male gender were associated with plaque presence in diabetic subjects. Plaque progression was significantly associated with age, the number of territories with basal plaque, smoking, and renal replacement therapy in both groups. Additionally, during a mean follow-up time of 48 months, CVE rate among participants without diabetes was 19.58 per 1000 person-years and 44.44 per 1000 person-years among participants with diabetes. After competing risk analyses and model selection, those variables that better predicted CVE in individuals without diabetes were the number of territories with plaque, age and serum concentrations of 25-OH vitamin D. Among participants with diabetes, the strongest model predicting incident CVE had only one variable: the number of territories with basal plaque. For both models, the concordance (C) index score was greater than 0.7 at both 24 and 48 months. We concluded that SA is more prevalent, carries a higher plaque burden, and is more progressive in CKD subjects with diabetes than in CKD subjects without diabetes. In these individuals, diabetes outweighs other risk factors associated with the presence of SA. SA is the strongest predictor of future CVE in diabetic individuals with CKD. Early detection of the SA burden by multi-territorial vascular ultrasound could improve CVE prediction in this population.

Background: Type 2 diabetes is a common disease with increased mortality and morbidity due to cardiovascular disease (CVD). This thesis is based on three studies that evaluated traditionally used and emerging risk markers to identify individuals with high-risk of developing CVD in middle-aged men and women with type 2 diabetes. One study was conducted to compare the equivalence between two different ultrasound techniques to measure intima-media thickness since IMT was used to evaluate subclinical atherosclerosis as a surrogate endpoint. Methods: Data from the cohort study, cardiovascular risk in type 2 diabetes – a prospective study in primary care (CARDIPP) was used in paper I, III and IV. In paper I, baseline data from the first 247 subjects was analysed. Associations between traditionally measured lipids, apolipoproteins, glycaemic control and low-grade inflammation and IMT were analysed. In paper III, the full baseline cohort, with data from 761 subjects from the CARDIPP study was cross-sectionally analysed regarding correlations between abdominal obesity measured as waist circumference (WC) and sagittal abdominal diameter (SAD), inflammatory markers and IMT and pulse wave velocity (PWV). In paper IV, the associations reported in paper I and III were prospectively investigated with data from the first year of follow-up four years after the baseline investigations in CARDIPP-revisited. In paper II a study was performed on 24 young healthy subjects, both men and women. IMT was measured in the common carotid artery (CCA) and in the abdominal aorta (AA), by two skilled ultrasonographers, with 2 different ultrasound techniques in a randomised order. Results: ApoB/apoA-I ratio (r=0.207, p=0.001), apoB (r=0.166, p=0.009) and non HDLcholesterol (nHDL-c) (0.129, p=0.046) correlated with IMT. In CCA IMT was equivalent using B-mode- and M-mode respectively. However in AA, IMT was 11.5% thicker using B-mode. Abdominal obesity were significantly correlated with; IL-6 and CRP (both p<0.001, WC and SAD respectively), IMT (WC p=0.012, SAD p=0.003) and PWV (p<0.001 WC and SAD respectively). Adjusting for age, sex, treatment with statins, systolic blood pressure (SBP), Body Mass Index (BMI), CRP and HbA1c, SAD (p=0.047) but not WC, remained associated with IMT. There were significant correlations between apoB (r=0.144, p=0.03) and CRP (r=0.172, p=0.009) measured at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r=0.130, p=0.049), WC (r=0.147, p=0.027) and SAD (r=0.184, p=0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p=0.036). Conclusions: There was a significant association between apoB/apoA-I ratio and IMT. The association was independent of conventional lipids, CRP, glycaemic control and use of statins. Both SAD and WC were associated with inflammation, atherosclerosis and arterial stiffness. However, SAD was slightly more robustly associated to subclinical organ damage, compared with WC. Prospectively; apoB and CRP, but not LDL-cholesterol predicted increased subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes. The two different ultrasound techniques, B-mode and M-mode, measured different IMT thickness in the aorta, emphasizing the importance of using similar technique when comparing the impact of absolute values of IMT on cardiovascular disease.

Objective: To examine the association between subclinical atherosclerosis (ascertained as coronary artery calcium; CAC) in asymptomatic individuals in the Central Appalachian region of the United States and individual- and geographic-level factors. Methods: Data were obtained from participants in CAC screening during 2012 and 2016. CAC score was assessed as CAC=0 (no plaque), 1≤CAC≤99 (mild plaque), 100≤CAC≤399 (moderate plaque), and CAC≥400 (severe plaque). Additionally, data on demographics (age, sex, and race), medical conditions, lifestyle factors, and family history of coronary artery disease (CAD) were obtained. Further, zip codes of place of residence for participants were used to generate geographic-level data. Descriptive statistics were used to estimate the prevalence of CAC, and multinomial logistic regression models were used to delineate significant factors. Results: Of 1512 participants, 57.6% had CAC>0. The prevalence of mild, moderate, and severe plaques was 31.6%, 16.3%, and 9.7%, respectively. Demographic, medical conditions, lifestyle factors, and family history of CAD were associated with increased risk for subclinical atherosclerosis. Further, the proportion of minority residents significantly increased the risk for severe plaque [RRR=1.06; p-value=0.04] and the proportion of residents on government assistance significantly decreased the risk for mild plaque [RRR=0.93; p-value=0.03]. Conclusion: The results imply that the proportion of minority residents in a geographic area is associated with increased relative risk for subclinical atherosclerosis, while the proportion of residents on government assistance decreased such risk. However, future geographic or neighborhood-level studies with larger sample size are needed to delineate further the consistency of these results in the Central Appalachian population.

Subclinical atherosclerosis is an important area of research to evaluate stroke risk and predict localization of plaque. The current methods for detecting atherosclerosis risk are insufficient because it is based on The Framingham Risk Score and carotid intima media thickness, therefore an engineering detection model based on quantifiable data is needed. Laminar and turbulent flow, dictated by Reynolds number and relative roughness, was modeled through the carotid artery bifurcation to compare shear stress and shear rate. Computer-aided design and fluid flow software were used to model hemodynamics through the carotid artery. Data from the model was derived from governing equations programmed in COMSOL for both laminar and turbulent flow. A carotid artery model is accurate enough to describe how relative roughness, flow profiles, and shear rate can be a good prediction of subclinical atherosclerosis.

Introduction: Patients with inflammatory polyarthritis (IP) have an excess risk of cardiovascular (CVD) mortality due to accelerated atherosclerosis. Markers identifying individuals with subclinical atherosclerosis as measured by carotid intima-medial thickness (cIMT) and plaque may allow for attenuation of CVD risk. The objective of this study was to identify associated risk markers for atheromatous plaque and cIMT in an incident cohort of patients with early IP and to assess the risk markers associated with progression of cIMT and plaque after 2 years of follow-up.Methods: From 2004 to 2008 consecutive patients with early IP (≥2 joints swollen for ≥4 weeks) aged 18-65 years, who were within 24 months of symptom onset (±6 months) were recruited as part of a primary-care-based inception cohort. Apparently healthy controls were recruited on a frequency matched 'buddy' pair system. Patients underwent joint and blood pressure examination. Patients and controls underwent BMI measurement and their medication was recorded. Patients' blood was taken for measurement of rheumatoid factor, anti-citrullinated protein antibody, C reactive protein, glucose, lipids (LDL, HDL, triglycerides, paroxonase 1, apolipoprotein A1 and B) and markers of vascular damage (E-selectin, VCAM) and adipocytokines (leptin and adiponectin). Patients and controls underwent B mode Doppler ultrasound examination of the carotid arteries to assess for cIMT and the presence of plaque. In univariate analyses we identified factors that were associated with cIMT and plaque presence after age and gender adjustment. An additive stepwise multivariable logistic regression model was created to investigate the independence of any associations.Results: The 329 IP subjects had a median (IQR) age of 51 (42-58) years and 96 (29%) were male. IP subjects were more likely to be smokers, have a family history of CVD, have diabetes, higher BP and be overweight than their apparently healthy counterparts. IP subjects with plaque at baseline often did not have prior CVD. Subjects with IP had a 2.87 fold higher plaque frequency at the baseline but a similar median cIMT relative to the controls. Traditional CVD risk markers such as age, systolic BP and LDL were associated with cIMT and plaque at baseline. Adiponectin levels were negatively associated with cIMT and positively associated with plaque. IP subjects had a significant increase in their cIMT in the first 2 years of follow-up. The rate of progression of cIMT was 1.5-2.2 fold greater in IP than reported in the general population. Novel risk factors added to the model above and beyond traditional risk factors in predicting atherosclerosis. Steroid exposure at 2 years was associated with atherosclerosis progression.Conclusion: Markers known to be associated with atherosclerosis in the general population are associated with cIMT and plaque presence in early IP prior to established inflammatory disease and therapy. While cIMT in subjects and controls was the same at baseline there was an accelerated rate of progression of cIMT in IP subjects relative to that reported in the general population.

Aim: To examine the association of cardiovascular disease risk factors with and their cumulative effect on coronary artery calcium in hard-to-reach asymptomatic patients with diabetes. Methods: : A total of 2563 community-dwelling asymptomatic subjects from Central Appalachia participated in coronary artery calcium screening at a heart centre. Binary variable was used to indicate that coronary artery calcium was either present or absent. Independent variables consisted of demographic and modifiable risk factors and medical conditions. Descriptive statistics and multinomial logistic regression analyses were conducted. Results: : In total, 55.8% and 13.7% of study participants had subclinical atherosclerosis (coronary artery calcium ⩾1) and diabetes, respectively. The presence of coronary artery calcium was higher in subjects with diabetes (68.5%) than those without (53.8%). Compared to subjects without diabetes with coronary artery calcium = 0, obesity, hypertension, hypercholesterolaemia and smoking increased the odds of the presence of coronary artery calcium (coronary artery calcium score ⩾1) regardless of diabetes status; however, with larger odds ratios in subjects with diabetes. Compared to subjects without diabetes with coronary artery calcium score = 0, having 3, 4 and ⩾5 risk factors increased the odds of presence of coronary artery calcium in subjects with diabetes by 14.06 (confidence interval = 3.26–62.69), 32.30 (confidence interval = 7.41–140.82) and 47.12 (confidence interval = 10.35–214.66) times, respectively. Conclusion: : There is a need for awareness about subclinical atherosclerosis in patients with diabetes and more research about coronary artery calcium in subpopulations of patients.

Acquired immunodeficiency syndrome (AIDS) is considered a global epidemic with over 65 million people worldwide infected with the HIV-1 virus, the causative agent [1]. The development of highly active antiretroviral therapy (HAART) has significantly increased the life expectancy of people infected with the virus by slowing the progression to the development of AIDS. However, the treatment has also led to the emergence of early onset cardiovascular complications including myocardial infarction [2] and atherosclerotic lesions [3], as well as subclinical markers of atherosclerosis including increased carotid artery intima-media thickness [4], increased arterial stiffness [5–6], and endothelial dysfunction [6]. It appears that HAART and HIV-1-infection are independent risk factors for the development of atherosclerosis in adults [7]; however, the mechanism of disease progression remains unclear. There is a pressing need to identify mechanisms of early on-set cardiovascular disease associated with HIV-1 infection and HAART and to identify therapeutic strategies to reduce cardiovascular disease in HIV patients. The overall goal of this study is to test the hypothesis that over-expression of HIV proteins will lead to alterations in the biomechanical properties of large arteries.

With over 33 million people infected with the human immunodefeciency virus (HIV-1), HIV-1 and autoimmune deficiency syndrome (AIDS) is a worldwide epidemic [1]. However, the development and widespread use of highly active antiretroviral therapy (HAART) has helped transform HIV-1 infection from a terminal disease leading to AIDS to a manageable chronic condition. With the increase in life expectancy, a new set of non-AIDS related complications has emerged including dyslipidemia, lipodystrophy, insulin resistance, diabetes mellitus, and cardiovascular disease (CVD) specifically high risks for myocardial infarction[2] and increased incidence of atherosclerosis [3]. Additionally, patients exhibit markers of subclinical atherosclerosis including endothelial dysfunction [4], carotid artery intima-media thickening [5], and arterial stiffening [4, 6].