Books on the topic 'Major cardiovascular events'

Mental stress, intrinsically subjective, lacks clear operationalization by any universally accepted gauge in routine clinical practice. There is not even an accepted single conceptualization of mental stress as opposed to the classic risk factors measured by, for example, resting blood pressure or low-density lipoprotein cholesterol among others. Yet, the link between psychosocial stress and cardiovascular events is a century-old intuition substantiated by many studies. Likely, mental stress affects cardiovascular health over the whole course of at-risk-stage up to cardiovascular events. This chapter discusses the major pathophysiologic effects of mental stress on cardiovascular pathogenesis.

Sport and exercise have been intensely advocated as protective lifestyle measures, preventing or reducing the risk of severe health issues including cardiovascular disease. More extreme forms of sport (for instance at high altitudes) have been identified as an important way of promoting cardiovascular adaptation, but have also been associated with adverse effects and even major cardiovascular events. More commonplace sport and exercise may also increase an individual’s risk of cardiac events. This publication is timely in the light of an increasing number of clinical papers in this field. The textbook provides an overview of prevention, detection, and treatment for elite athletes and young sports professionals in training which will be useful for clinical cardiologists, sports physicians, and general physicians alike. Split into eleven key areas in sports cardiology, ranging from sudden cardiac death in athletes to cardiovascular effects of substance of abuse/doping, the text is an invaluable resource covering all aspects of sports cardiology.

This chapter provides a brief summary of the immune pathogenesis of atherosclerosis, highlighting shared features with inflammatory pathways in rheumatoid arthritis (RA) described in detail in Chapter 25.4. RA constitutes a prototype autoimmune disease primarily affecting the joints but also the heart and vessels associated with increased cardiovascular mortality. Recent years have produced a wealth of novel insights into the diversity of immune cell types which either propagate or dampen inflammation in atherogenesis. Expansion of this inherent anti-inflammatory component carried by regulatory T cells may constitute a new therapeutic target to harness the progression of atherosclerotic cardiovascular disease. Among the various inflammatory mediators involved in RA pathology, cytokines (tumour necrosis factor-α‎ and interleukin-6) have gained major interest as therapeutic targets with approved therapies available. In light of the many common features in the pathogenesis of RA and atherosclerosis, these biologics are currently being evaluated in cardiovascular patients. The recently published CANTOS trial showed that IL-1 inhibition reduced adverse cardiovascular events in patients with coronary artery disease demonstrating that inflammation is a genuine therapeutic target. The near future will provide more information whether inflammation is a bona fide cardiovascular risk factor based on completion of several clinical trials using anti-inflammatory approaches in patients with both cardiovascular disease and rheumatoid arthritis.

Prevention of hypertension can help prevent cardiovascular disease and renal complications. Obesity, a high sodium and low potassium intake, physical inactivity, and high alcohol consumption all contribute to the development of hypertension, and randomized controlled trials have shown that appropriate lifestyle modifications are able to reduce blood pressure and/or prevent the development of hypertension. The major complications of hypertension are stroke, coronary heart disease, heart failure, peripheral artery disease, and chronic kidney disease. Multiple randomized controlled trials and their meta-analyses have shown that treatment with antihypertensive drugs reduces the incidence of fatal and non-fatal cardiovascular events. In addition, meta-analyses have shown that there are no clinically relevant differences in the effects of the five major drug classes on outcome, so all of them are considered suitable for the initiation and maintenance of antihypertensive therapy. Nevertheless, the therapeutic approach in the elderly, women, and patients with diabetes, cerebrovascular, cardiac, or renal disease deserves special attention.

Higher organisms have a cardiovascular circulatory system with blood vessels to supply vital nutrients and oxygen to distant tissues. It is therefore not surprising that vascular disorders are leading causes of mortality. Understanding how new blood vessels form, creates opportunities to cure these life-threatening diseases. After birth, growth of blood vessels mainly occurs via two distinct mechanisms depending on the initial trigger: angiogenesis (referred here as capillary sprouting) is induced primarily by hypoxia, whereas arteriogenesis (referred here as the rapid enlargement of pre-existing collateral arteries, induced by vascular occlusion) is mainly driven by fluid shear stress. Arteriogenesis allows conductance of much larger volumes of blood per unit of time than does the increase in capillary density during angiogenesis. Notwithstanding these major differences, angiogenesis and arteriogenesis share a number of underlying mechanisms, e.g. the involvement of growth factor signalling. This chapter highlights the cellular and molecular events driving the two processes and discusses the therapeutic potential of targeting angiogenesis in cancer and arteriogenesis in cardiovascular diseases.

This chapter, found in the chest pain section of the book, provides a succinct synopsis of a key study examining the use of computed tomography (CT) coronary artery calcium score for cardiovascular risk stratification. This summary outlines the study methodology and design, major results, limitations and criticisms, related studies and additional information, and clinical implications. Researchers report that adding coronary artery calcium score to traditional risk factors produces significant improvements in classification of patients for future risk of coronary heart disease events, especially for intermediate-risk individuals who stand to benefit the most from a risk stratification strategy. In addition to outlining the most salient features of the study, a clinical vignette and imaging example are included in order to provide relevant clinical context.

The risk of developing cardiovascular (CV) disease is increased in patients with chronic kidney disease (CKD) and although dyslipidaemia is a major contributory factor to the development of premature CV disease, the relationship is complex. Changes in lipid fractions are related to glomerular filtration rate and the presence and severity of proteinuria, diabetes, and other confounding factors. The spectrum of CV disease changes from lipid-dependent, atheromatous coronary disease in early CKD to lipid-independent, non-coronary disease, manifesting as heart failure, and sudden cardiac death in advanced and end-stage renal disease. Statin-based lipid-lowering therapy is proven to reduce coronary events across the spectrum of CKD. The relative reduction in overall CV events, however, diminishes as CKD progresses and the proportion of lipid-dependent coronary events declines. There is nevertheless a strong argument for the use of statin-based therapy across the spectrum of CKD. The argument is particularly strong for those patients with progressive renal disease who will eventually require transplantation, in whom preventive therapy should start as early as possible. The SHARP study established the benefits and endorses the use of lipid-lowering therapy in CKD 3-4 but uncertainty about the value of initiation of statin therapy in CKD 5 remains. There is, however, no rationale for stopping agents started earlier in the course of the illness for compelling indications, particularly in those who will ultimately be transplanted. The place of high-density lipoprotein-cholesterol raising and triglyceride lowering therapy needs to be assessed in trials. Modifying dyslipidaemia in CKD has demonstrated that lipid-dependent atheromatous cardiovascular disease is only one component of the burden of CV disease in CKD patients, that this is proportionately less in advanced CKD, and that modification of lipid profiles is only one part of CV risk management.

Psoriasis is a common chronic inflammatory disorder of the skin that is associated with multisystem effects. Approximately 125 million people worldwide are affected by psoriasis, nearly one quarter of whom have moderate to severe disease. The majority of patients with psoriasis have a waxing and waning course with variable periods of spontaneous disease improvement or clearance. A rapidly expanding body of epidemiologic literature suggests psoriasis to be associated with a greater comorbid disease burden than patients without psoriasis. In addition to psoriatic arthritis, cardiometabolic diseases, including metabolic syndrome and its component disorders, as well as major adverse cardiovascular events are the most common comorbidities of psoriasis; together they are the primary cause of premature mortality among moderate to severe psoriasis patients. Continued efforts to better understand currently known and identify other emerging comorbidities of psoriasis are critical.

The spread of non-communicable diseases (NCDs) is a barrier to the development of goals including reduction of poverty, health equity, economic stability, and human security. NCDs accounted for 61% of the estimated 58 million deaths and 46% of the global burden of diseases worldwide in 2005. Among NCDs, chronic kidney disease (CKD) is of particular significance. It is recognized that the burden of CKD is not only limited to its impact on demands for renal replacement therapy but has equally major impacts on the health of the overall population. For example, it is now well established that among the general population as well as in the diabetic or hypertensive population, the prognosis, especially the mortality and acceleration of cardiovascular events, depends on kidney involvement. Also, CKD is associated with other major serious consequences including increased risk of acute kidney injury, increased risk of mineral and bone disease, adverse metabolic and nutritional consequences, infections, and reduced cognitive function. As a consequence of these amplifying effects, the financial expenditure and medical resources consumed for the management of CKD patients is much higher than expected. The burden of CKD is likely to have profound socioeconomic and public health consequences in developing countries.

Chronic kidney disease (CKD) is associated with a variety of outcomes, some of which are directly and indirectly related to kidney disease, but which ultimately impact on patients’ quality of life and long-term outcomes. The events to which people with CKD are exposed ultimately determine their risk and prognosis of both progression to needing renal replacement therapy, or other morbidities and mortalities. The notion of competing risk is important. The five major outcomes of CKD are: progression of CKD, progression to ESRD (either dialysis or transplantation); death; cardiovascular events; infections; and hospitalizations. Where data is available, not only the risk of the specific outcome, but the factors which may predict those outcomes are described. Each section describes what is currently known about the frequency of the outcome, the limitations of that knowledge, the risk factors associated with outcome, and implications for care and future research. Available published literature often describes outcomes in CKD populations as if it is a homogenous group of patients. But it is well documented that outcomes in those with CKD differ depending on stage or severity, and whether they are or are not known to specialists. Where possible, each section ensures that the specific CKD cohort(s) from which the information is derived is clearly described.

Arterial diseases are heavily intertwined with atherosclerosis and coronary artery disease and the presence of both symptomatic and asymptomatic peripheral artery diseases is known to affect the rate of cardiovascular events and deaths. Screening for abdominal aortic aneurysm (AAA) in selected populations is also a major issue for the cardiologist. Additionally, intima-media thickness and ankle-brachial index (ABI) measurements, screening for carotid or femoral plaques, and new techniques looking at the rigidity and elasticity of arteries may further help with risk stratification, especially in intermediary risk populations. Cardiologists may also encounter other conditions such as subclavian artery disease, arterial dissection, arterial entrapment, and arteritis (e.g. giant cell or Takayasu’s arteritis). Even if they don’t undertake imaging themselves, they should know about these diseases and when to refer patients. Although cardiac and vascular ultrasounds are complementary, they require a completely different skill set and formal training. The ultimate goal of this chapter is to define the basic principles that any cardiologist should know, and also provide guidance to cardiologists more interested in vascular diseases. For the benefit of the patient there is a need for collaboration between the different disciplines involved in vascular diseases according to local medical availability and skill.

The goals of treatment in renal vasculitis are to stop vasculitic activity and recover renal function. Subsequent strategies are required to prevent vasculitis returning and to address longer-term co-morbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk.Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as azathioprine, to prevent relapse. Plasma exchange improves renal recovery in severe presentations. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Methotrexate is effective in non-renal vasculitis but difficult to use in patients with renal impairment. Mycophenolate mofetil seems to be effective but there is less long-term evidence.Drug toxicity contributes to co-morbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn.Disease relapse occurs in about 50% of patients. Early detection is less likely to lead to an adverse affect on outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator.Renal impairment at diagnosis is a strong predictor of patient survival and renal outcome. Other predictors include patient age, antineutrophil cytoplasmic antibody subtype, disease extent and response to therapy. Chronic kidney disease can stabilize for many years but the risks of end-stage renal disease are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful with similar outcomes to other causes of end-stage renal disease.

Cardiac arrest in the perioperative period is distinct from cardiac arrest in other scenarios, given that the event is typically witnessed and real-time vital signs are often being monitored. Additionally, having a mental framework by which to consider and refine the differential diagnosis is paramount, as this then guides the selection of a suitable treatment plan. However, in order to establish the correct diagnosis, one must have an adequate understanding of normal cardiac physiology, of cardiovascular pathology, and the ways in which this may adversely affect cardiac function. This chapter provides an overview of how to approach the patient with cardiovascular instability. Subsequent chapters in this section discuss specific treatment plans for the major life-threatening pathophysiologies one could encounter.

Preoperative risk assessment is one of the most important steps in perioperative management. In the last decades, considerable progress has been achieved. However, as more high-risk procedures are performed in more aged patients, suffering more morbidity, this may lead to an increased risk of adverse outcomes. The goal of preoperative assessment is to identify patients at extreme risk and discuss whether they should be operated on, or undergo an alternative procedure with a lower risk profile, or if conservative treatment should be continued. Furthermore, it gives the opportunity to optimize patients prior to surgery, adapt intraoperative anaesthetic management and monitoring, and select patients for postoperative treatment at an intensive care unit or post-anaesthesia care unit. The cornerstone of preoperative assessment is the estimation of functional capacity. Accurate anamnesis and physical examination are crucial. Several procedures have been used to optimize the preoperative risk stratification. In this chapter, the value of these additional preoperative investigations is reviewed. These investigations are to be performed only in patients with considerable co-morbidity undergoing high-risk surgery. As cardiovascular adverse events are a major determinant of postoperative outcome, the chapter focuses on the management of the two most important cardiac risk factors, that is, myocardial ischaemia and impaired left ventricular function.

Perioperative risk assessment is essential in screening patients before noncardiac surgery. Cardiovascular complications such as fatal and non-fatal myocardial infarction (MI), ventricular arrhythmia, pulmonary edema, and stroke are important in-hospital causes of morbidity and mortality intra and post-operatively. The optimal approach is to identify patients at increased risk so that appropriate testing and therapeutic interventions are undertaken a priori to minimize such risk. The initial preoperative evaluation includes identification of surgery-specific risk, patient exercise functional capacity and clinical risk profile. Patients with major predictors of events such as acute coronary syndromes, recent MI, unstable arrhythmia, and severe valvular disease warrant further management and optimization that often lead to delaying surgery. Those with three or more predictors (history of ischemic heart disease, compensated heart failure, diabetes, renal insufficiency, or history of cerebrovascular disease) undergoing high- risk surgery often require stress testing. Although data from randomized prospective trials are lacking, numerous studies have demonstrated the utility of myocardial perfusion imaging (MPI) for determination of perioperative cardiac risk. The goal of this chapter is to review the use of MPI for preoperative risk assessment and the recommendations from the current guidelines. The focus will be on short-term and long-term prognosis including special groups such as after coronary stenting and before vascular surgery, liver and renal transplantation.

The goals of treatment in anti-neutrophil cytoplasm antibody (ANCA) vasculitis are to stop vasculitic activity, to prevent vasculitis returning, and to address longer-term comorbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk. Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as methotrexate or azathioprine, to prevent relapse. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Additional therapy with intravenous methylprednisolone and plasma exchange is employed in severe presentations with failing vital organ function. Drug toxicity contributes to comorbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem, with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn. Disease relapse occurs in 50% and requires early detection at a stage when it will not adversely affect outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator. Outcomes of vasculitis depend heavily on the level of tissue damage at diagnosis, especially renal dysfunction, but are also influenced by patient age, ANCA subtype, disease extent, and response to therapy. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)is treated along similar principles to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis but the persistence of steroid-dependent asthma in over one-third and differences in pathogenesis has suggested alternative treatment approaches. Chronic morbidity results from tissue damage and is especially common in the upper and lower respiratory tract and kidneys. Tracheobronchial disease is a severe late complication of GPA, while deafness, nasal obstruction, and chronic sinusitis are sequelae of nasal and ear vasculitis. Chronic infection of damaged epithelial surfaces acts as a drive for vasculitic activity and adequate infection control is necessary for stable remission. Chronic kidney disease can stabilize for many years but the risks of endstage renal disease (ESRD) are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful, with similar outcomes to other causes of ESRD.

Arrhythmogenic cardiomyopathy is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias and pathologically by an acquired and progressive dystrophy of the ventricular myocardium with fibrofatty replacement. The clinical manifestations of arrhythmogenic cardiomyopathy vary according to the ‘phenotypic’ stage of the underlying disease process. Since there is no ‘gold standard’ to reach the diagnosis of arrhythmogenic cardiomyopathy, multiple categories of diagnostic information have been combined. Different diagnostic categories include right ventricular morphofunctional abnormalities (by echocardiography and/or angiography and/or cardiovascular magnetic resonance imaging), histopathological features on endomyocardial biopsy, electrocardiogram, arrhythmias, and family history, including genetics. The diagnostic criteria were revised in 2010 to improve diagnostic sensitivity, but with the important prerequisite of maintaining diagnostic specificity. Quantitative parameters have been put forward and abnormalities are defined based on the comparison with normal subject data. A definite diagnosis of arrhythmogenic cardiomyopathy is achieved when two major, or one major and two minor, or four minor criteria from different categories are met. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, sarcoidosis, dilated cardiomyopathy, right ventricular infarction, congenital heart diseases with right ventricular overload, and athlete’s heart. Among diagnostic tools, contrast-enhanced cardiovascular magnetic resonance is playing a major role in detecting subepicardial-midmural left ventricular free wall involvement, even preceding morphofunctional abnormalities. Moreover, electroanatomical mapping is an invasive tool able to detect early right ventricular free wall involvement in terms of low-voltage areas. Both techniques are increasingly used in the diagnostic work-up although are not yet part of diagnostic criteria.

This chapter examines the bidirectional relationship between depression and stroke. It is now clearly established that depression is a significant risk factor for stroke, and vice-versa. We review the main biological and demographic factors underlying the association between stroke and depression, the predicted mortality, the mechanism of post-stroke depression, and recent findings on its pharmacological prevention. We conclude by stressing the need for developing effective strategies to manage the burden of illness associated with these interacting conditions. As with the cardiovascular system depression has major effects on the occurrence of stroke. Morbidity and mortality are increased for patients with cerebral vascular accidents (CVA) who are depressed and is seen even in a 10-year follow-up. Depression should be treated concurrently with the management of the acute phase of a CVA.

Excess protein in the urine almost always comes from the kidney. Proteinuria up to 150 mg/day in an adult (protein:creatinine ratio (PCR) up to 15 mg/mmol) is considered normal. Daily average excretion is 80 mg, of which about 30 mg is albumin that has been filtered and not reabsorbed. Other components comprise low-molecular-weight filtered proteins that have escaped reabsorption, and proteins secreted or lost into urine from cells of the nephron. Increased permeability of the glomerulus to high-molecular-weight proteins is the most common cause of the clinically detected proteinuria, and albumin is the major component of excess glomerular proteinuria. Even small amounts of proteinuria are associated with increased cardiovascular risk and long-term renal risk. In patients with renal disease, regardless of type, proteinuria is a strong predictor of loss of glomerular filtration rate and proteinuria at levels higher than an equivalent of 1 g/24 hours can be considered high renal risk. This limit should be lowered in young patients, and if microscopic haematuria is also present. For both cardiovascular and renal outcomes, risk is graded with severity of proteinuria. In routine clinical practice, ratios of albumin or total protein to creatinine level (ACR or PCR) in spot urine samples are usually more pragmatic and useful than 24-hour collections. ACR is more sensitive as a screening test (normal range up to 2.5 mg/mmol in men, 3.5 mg/mmol in women).

Even if sudden cardiac death is considered to be the most frequent cause of death in adults in industrialized countries, its incidence varies widely, depending on the definition and the source and quality of underlying data. It is estimated that about 70-80% of cases are due to coronary heart disease. The remaining 20% are attributable to a wide variety of inborn, genetically determined or acquired diseases, including a small group with hitherto undefined background. Prevention primarily encompasses the treatment of cardiovascular risk factors to avoid manifestations of coronary heart disease. Furthermore, preventive strategies are targeted to define groups of patients with an increased risk for sudden cardiac death or individuals at risk in specific populations, e.g. competitive athletes. A major target group are patients with impaired left ventricular function, preferentially due to myocardial infarction. These patients, and some less clearly defined patient groups with non-ischaemic cardiomyopathy and heart failure, may benefit from the insertion of an implantable cardioverter-defibrillator. With regard to pharmacological prevention, treatment of the underlying condition is the mainstay, since no antiarrhythmic substance-with the exemption of beta-blockers in some situations-has shown to be of efficacy.

Any public debate about air pollution starts with the premise that air pollution cannot be good for you, so we should have less of it. However, it is much more difficult to determine how much is dangerous, and even more difficult to decide how much we are willing to pay for improvements in measured air pollution. Recent UK estimates suggest that fine particulate pollution causes about 6500 deaths per year, although it is not clear how many years of life are lost as a result. Some deaths may just be brought forward by a few days or weeks, while others may be truly premature. Globally, household pollution from cooking fuels may cause up to two million premature deaths per year in the developing world. The hazards of black smoke air pollution have been known since antiquity. The first descriptions of deaths caused by air pollution are those recorded after the eruption of Vesuvius in ad 79. In modern times, the infamous smogs of the early twentieth century in Belgium and London were clearly shown to trigger deaths in people with chronic bronchitis and heart disease. In mechanistic terms, black smoke and sulphur dioxide generated from industrial processes and domestic coal burning cause airway inflammation, exacerbation of chronic bronchitis, and consequent heart failure. Epidemiological analysis has confirmed that the deaths included both those who were likely to have died soon anyway and those who might well have survived for months or years if the pollution event had not occurred. Clean air legislation has dramatically reduced the levels of these traditional pollutants in the West, although these pollutants are still important in China, and smoke from solid cooking fuel continues to take a heavy toll amongst women in less developed parts of the world. New forms of air pollution have emerged, principally due to the increase in motor vehicle traffic since the 1950s. The combination of fine particulates and ground-level ozone causes ‘summer smogs’ which intensify over cities during summer periods of high barometric pressure. In Los Angeles and Mexico City, ozone concentrations commonly reach levels which are associated with adverse respiratory effects in normal and asthmatic subjects. Ozone directly affects the airways, causing reduced inspiratory capacity. This effect is more marked in patients with asthma and is clinically important, since epidemiological studies have found linear associations between ozone concentrations and admission rates for asthma and related respiratory diseases. Ozone induces an acute neutrophilic inflammatory response in both human and animal airways, together with release of chemokines (e.g. interleukin 8 and growth-related oncogene-alpha). Nitrogen oxides have less direct effect on human airways, but they increase the response to allergen challenge in patients with atopic asthma. Nitrogen oxide exposure also increases the risk of becoming ill after exposure to influenza. Alveolar macrophages are less able to inactivate influenza viruses and this leads to an increased probability of infection after experimental exposure to influenza. In the last two decades, major concerns have been raised about the effects of fine particulates. An association between fine particulate levels and cardiovascular and respiratory mortality and morbidity was first reported in 1993 and has since been confirmed in several other countries. Globally, about 90% of airborne particles are formed naturally, from sea spray, dust storms, volcanoes, and burning grass and forests. Human activity accounts for about 10% of aerosols (in terms of mass). This comes from transport, power stations, and various industrial processes. Diesel exhaust is the principal source of fine particulate pollution in Europe, while sea spray is the principal source in California, and agricultural activity is a major contributor in inland areas of the US. Dust storms are important sources in the Sahara, the Middle East, and parts of China. The mechanism of adverse health effects remains unclear but, unlike the case for ozone and nitrogen oxides, there is no safe threshold for the health effects of particulates. Since the 1990s, tax measures aimed at reducing greenhouse gas emissions have led to a rapid rise in the proportion of new cars with diesel engines. In the UK, this rose from 4% in 1990 to one-third of new cars in 2004 while, in France, over half of new vehicles have diesel engines. Diesel exhaust particles may increase the risk of sensitization to airborne allergens and cause airways inflammation both in vitro and in vivo. Extensive epidemiological work has confirmed that there is an association between increased exposure to environmental fine particulates and death from cardiovascular causes. Various mechanisms have been proposed: cardiac rhythm disturbance seems the most likely at present. It has also been proposed that high numbers of ultrafine particles may cause alveolar inflammation which then exacerbates preexisting cardiac and pulmonary disease. In support of this hypothesis, the metal content of ultrafine particles induces oxidative stress when alveolar macrophages are exposed to particles in vitro. While this is a plausible mechanism, in epidemiological studies it is difficult to separate the effects of ultrafine particles from those of other traffic-related pollutants.