Haematocrit: a predictor of cardiovascular mortality ?

Abstract. Objectives. The main purpose of the study was to assess a possible association between haematocrit (Hct) and long-term cardiovascular disease (CVD) mortality. Design. An extensive examination programme was carried out in 2014 men, defined as apparently healthy, during the period 1972 to 1975, including Hct measurements in a 25% random subsample. Sequential, cause-specific mortality was followed prospectively over a period of 16 years. Setting. The survey was conducted at Medical Department B, Rikshospitalet, Oslo, Norway. Subjects. The participants represented 86% of all eligible apparently healthy men working in five preselected companies in Oslo. Interventions. No intervention was given by the study group during follow-up. Main outcome measures. Complete, cause-specific mortality figures after 8–16 years were obtained from the Norwegian Central Bureau of Statistics. Results. Hct measures were obtained in 488 men (24.2%). Mean Hct was 47.2% (sd 2.9%). After correcting for differences in age, plasma cholesterol, systolic blood pressure, erythrocyte sedimentation rate and smoking habits (Cox proportional hazards model), an increase in Hct by 2 SDS was associated with an increase in CVD mortality by a factor ranging between 2.9 at 10, and 1.9 at 16 years (P < 0.05). A similar increased risk was observed earlier during follow-up but the number of deaths was too small for meaningful statistical analysis. No association was found between Hct and non-CVD mortality. Conclusions. Our data show that increased Hct is associated with an increased risk of dying from CVD—independent of conventional CVD risk factors.     

Haematocrit,hypertension and risk of stroke

Abstract. Objectives . To assess the relationship between haematocrit and risk of stroke. Design . Prospective study of a cohort of men followed up for 9.5 years. Setting . General practices in 24 towns in England, Scotland and Wales (British Regional Heart Study). Subjects . A total of 7735 men aged 40–59 years at screening, selected at random from one general practice in each of 24 towns. Main outcome measures . Fatal and non-fatal strokes. Results . During a follow-up period of 9.5 years for all men there were 123 stroke events (33 fatal) in the 7346 men in whom the haematocrit level had been determined. In the cohort as a whole, risk of stroke was significantly raised at haematocrit levels ≥ 51% (relative risk [RR] = 2.5; 95% confidence intervals [CI] 1.2–5.0) after adjustment for age, social class, smoking, body mass index, physical activity, presence of diabetes and pre-existing ischaemic heart disease. Further adjustment for systolic blood pressure did not attenuate this association (RR = 2.4; 95% CI 1.2–4.9). A raised haematocrit was associated with an increase of stroke only in men with hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 90 mmHg or on regular antihypertensive treatment). No increased risk of stroke was seen at the higher haematocrit level (≥ 51%) in normotensive men. At haematocrit levels below 51%, hypertension was associated with a three-fold increase in risk of stroke compared with normotension (RR = 3.4, 95% CI 2.3, 5.1). At haematocrit levels 51%, hypertension was associated with a nine-fold increase in risk of stroke compared with normotension (RR = 9.3; 95% CI 4.2, 21.0). Exclusion of men receiving regular antihypertensive therapy did not alter the strong associations seen. Conclusion . The data suggest that an elevated haematocrit is an independent risk factor for stroke and that it interacts synergistically with elevated blood pressure.     

Haematocrit and risk of development of Type 2 diabetes mellitus in middle-aged Japanese men.

AIMS: To investigate the association between haematocrit and risk of development of diabetes. Methods The study enrolled 2953 normoglycaemic [fasting plasma glucose (FPG) < 6.1 mmol/l and taking no hypoglycaemic medication] Japanese men aged 35-59 years and free of medication for hypertension and history of cardiovascular disease. FPG was measured at periodic annual health examinations from May 1994 through May 2001. Men in whom Type 2 diabetes mellitus (FPG > or = 7.0 mmol/l or receiving hypoglycaemic medication) was found during repeated surveys were classified as having Type 2 diabetes. RESULTS: The estimated incidence rates for Type 2 diabetes during 7 years of follow-up were 3.1% [[95% confidence interval (CI) 1.6, 4.6]], 4.6% (2.8, 6.4), 5.0% (3.2, 6.9), 6.4% (4.4, 8.5), and 11.5% (8.9, 14.2) for respective haematocrit levels of < 42.6, 42.6-44.0, 44.1-45.3, 45.4-46.8, and >/= 46.9% (the log-rank test: P < 0.001). After controlling for potential predictors of diabetes, the respective relative risks for Type 2 diabetes were 1.0 (reference), 1.52 (95% CI 0.81, 2.86), 1.24 (0.66, 2.31), 1.57 (0.86, 2.88), and 2.30 (1.30, 4.08) (P for trend = 0.002). From stratified analyses by presence or absence of a risk factor, a linear association of haematocrit level with risk of development of Type 2 diabetes was also observed. CONCLUSION: These results indicate that haematocrit contributes to the risk of developing Type 2 diabetes.     

Rosiglitazone and cardiovascular risk

A meta-analysis of 42 clinical trials suggested that rosiglitazone, a widely used thiazolidinedione, was associated with a 43% greater risk of myocardial infarction (P = 0.03) and a 64% greater risk of cardiovascular death (P = 0.06). However, a number of criticisms have been raised that potentially undermine the conclusions of this analysis. In this article, we point out some of these limitations, summarize the currently available evidence concerning rosiglitazone and cardiovascular risk, share implications for drug safety evaluation, and offer practical recommendations to health care providers. We conclude that the data showing the increased risk for myocardial infarction and death from cardiovascular disease for diabetic patients taking rosiglitazone are inconclusive.     

Chemokines and cardiovascular risk

Based on the importance of inflammation in atherogenesis, recent work has focused on whether plasma markers of inflammation can noninvasively diagnose and prognosticate atherosclerotic disorders. Although several studies support an important pathogenic role of chemokines in atherosclerosis, potentially representing attractive therapeutic targets in atherosclerotic disorders, this does not necessarily mean that chemokines are suitable parameters for risk prediction. In fact, the ability to reflect upstream inflammatory activity, stable levels in individuals, and high stability of the actual protein (eg, long half-life and negligible circadian variation) are additional important criteria for an ideal biomarker in cardiovascular disease. Although plasma/serum levels of certain chemokines (eg, interleukin- 8/CXCL8 and monocyte chemoattractant protein-1/CCL2) have shown to be predictive for future cardiac events in some studies, their role as clinical biomarkers is unclear, and their ability to predict subclinical atherosclerosis has been disappointing. Further prospective studies, including a larger number of patients, are needed to make any firm conclusion. Based on the participation of several chemokines in atherogenesis, it is possible that in the future, combined measurements of multiple chemokines could reveal as a "signature of disease" that can serve as a highly accurate method to assess for the presence of atherosclerotic disease.     

Hyperglycaemia and cardiovascular risk

Cardiovascular diseases represent, today, the principal cause of mortality in the general population, especially in subjects with type 2 diabetes mellitus. In these patients the risk of death from cardiovascular diseases is equal to that of non-diabetic subjects with a previous episode of myocardial infarction. Many factors concur to determine such high risk. Hyperglycaemia contributes to the increase in morbidity and cardiovascular mortality associated with diabetes mellitus. Hyperglycaemia acts as a multiplier of cardiovascular risk due to frequent association of multiple risk factors in diabetic patients. Therefore, effective treatment requires a more complete assessment of quantitative and qualitative aspects of glycemic control as well as all components of the diabetic syndrome or, more commonly, metabolic syndrome.     

Glucose and cardiovascular risk

The American Diabetes Association and the World Health Organisation have recently redefined the spectrum of abnormal glucose tolerance. The criteria for diabetes mellitus were sharpened and impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were classified as intermediate stages between normal glucose homeostasis and diabetes, based on fasting and challenged glucose levels, respectively. Criteria were established for 'the metabolic syndrome', as a cluster of cardiovascular risk factors that frequently coincides with the abnormal glucose tolerance state. The extent to which the glucose level itself should be regarded as a cardiovascular risk factor is the subject of ongoing debate. Recent research suggests that cardiovascular risk is related to the plasma glucose level even in the normal range of glucose concentrations. The impact of glucose in relation to cardiovascular events is discussed in this review.     

Testosterone and cardiovascular risk

Cardiovascular (CV) disease is one of the most common causes of death in the western populations and, nowadays, its incidence is increasing even in the developing countries; although CV disease affects both sexes, it is more frequent in males in whom it shortens the average life expectancy. In this regard, this difference has been wrongly attributed for many years to the negative effects of testosterone (T); however, nowadays, a large amount of evidence suggests that this hormone may have protective effects on the CV system and that, indeed, the low levels of T could be associated with an increased CV risk and with an augmentation of morbidity and mortality in males. Such an aspect gains great relevance in light of the consideration that T decrease, besides occurring as a consequence of rare pathological conditions, can often take place with natural aging, causing a state of “male menopause”, also called late-onset hypogonadism. In this review, we aimed to summarize the present state of the art concerning the association between T deficit and CV disease by analyzing the protective role of T on CV system and the relationship of this hormonal lack with metabolic syndrome, CV morbidity and mortality, and with the CV complications, such as ischemic heart disease, heart failure and stroke, that frequently occur in T deficiency.     

Aldosterone and cardiovascular risk

Through its classic effects on sodium and potassium homeostasis, aldosterone, when produced in excess, is associated with the development of hypertension and hence with higher cardiovascular and renal risk. In recent years, experimental and epidemiologic data have suggested that aldosterone also may be linked to high cardiovascular risk independently of its effects on blood pressure. Thus, aldosterone has been associated with obesity and metabolic syndrome in selected populations, and these associations may further contribute to the higher cardiovascular risk of subjects with elevated aldosterone levels. Moreover, aldosterone has been reported to promote inflammation, oxidative stress, and fibrosis in a number of tissues. Clinical evidence indicates that patients with primary hyperaldosteronism have a higher risk of developing cardiovascular and renal complications than patients with essential hypertension who have the same level of blood pressure. Aldosterone receptor blockade has been shown to lower cardiovascular mortality after myocardial infarction and in patients with congestive heart failure. Some studies have also demonstrated that aldosterone blockade could have a favorable impact on the progression of renal disease. However, prospective interventional trials are needed to further evaluate the impact of blockade of aldosterone on cardiovascular risk.     

Obesity and cardiovascular risk

Obesity has assumed epidemic proportions and is expected to decrease the life expectancy of current and future generations by its cardiovascular complications and other associated chronic diseases. Recognizing the gravity of this trend, the American Heart Association recently identified obesity as an independent and important modifiable risk factor for cardiovascular disease. Obesity is known to cluster with other cardiovascular and metabolic risk factors constituting the cardiometabolic syndrome. The pathophysiogic link between obesity and cardiovascular disease is complex and involves multiple metabolic and inflammatory risk factors. In an attempt to better elucidate this major public health problem, this article reviews obesity as an epidemic, the structural and functional changes in the cardiovascular system as a result of obesity, and the pathophysiology of obesity-related cardiomyopathy. The sheer magnitude of the problem of obesity with its immense cardiovascular consequences warrants immediate intervention.     

Microalbuminuria and cardiovascular risk

Microalbuminuria is a marker for generalized vascular dysfunction. Its prevalence in United States and European general population surveys ranges from 6% to 10%. Increased risk for cardiovascular morbidity and mortality begins with albumin excretion rates that are well within normal limits. Although microalbuminuria interacts with the traditional cardiovascular risk factors, it has an independent relationship to renal and cardiovascular outcomes. For example, microalbuminuria doubles the risk for a cardiovascular event in patients with type 2 diabetes mellitus even after adjusting for the usual risk factors. Elevated rates of urinary albumin excretion predict target organ damage, notably renal disease, but are also related to left ventricular dysfunction, stroke, and myocardial infarction. Screening for microalbuminuria, which is recommended by several expert committees and associations, has become a readily accessible procedure. Screening can give clinicians prognostic information concerning cardiovascular risk and assist in guiding therapy. The goal of treatment is to prevent progression of, and even to reverse, microalbuminuria. Abundant evidence demonstrates that antihypertensive therapy is an important key to the control of urinary albumin excretion, and blockade of the renin-angiotensin system (with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) is the treatment of choice. These drugs have successfully halted or delayed the progression to nephropathy and have reversed elevated rates of albumin excretion to normal values, even when blood pressure reduction has been minimal.