Isolated low levels of high-density lipoprotein cholesterol are associated with an increased risk of coronary heart disease: an individual participant data meta-analysis of 23 studies in the Asia-Pacific region.

BACKGROUND: Previous studies have suggested that there is a novel dyslipidemic profile consisting of isolated low high-density lipoprotein cholesterol (HDL-C) level that is associated with increased risk of coronary heart disease, and that this trait may be especially prevalent in Asian populations. METHODS AND RESULTS: Individual participant data from 220 060 participants (87% Asian) in 37 studies from the Asia-Pacific region were included. Low HDL-C (HDL <1.03 mmol/L in men and <1.30 mmol/L in women) was seen among 33.1% (95% confidence interval [CI], 32.9-33.3) of Asians versus 27.0% (95% CI, 26.5-27.5) of non-Asians (P<0.001). The prevalence of low HDL-C in the absence of other lipid abnormalities (isolated low HDL-C) was higher in Asians compared with non-Asians: 22.4% (95% CI, 22.2-22.5) versus 14.5% (95% CI, 14.1-14.9), respectively (P<0.001). During 6.8 years of follow-up, there were 574 coronary heart disease and 739 stroke events. There was an inverse relationship between low HDL-C with coronary heart disease in all individuals (hazard ratio, 1.57; 95% CI, 1.31-1.87). In Asians, isolated low levels of HDL-C were as strongly associated with coronary heart disease risk as low levels of HDL-C combined with other lipid abnormalities (hazard ratio, 1.67 [95% CI, 1.27-2.19] versus 1.63 [95% CI, 1.24-2.15], respectively). There was no association between low HDL-C and stroke risk in this population (hazard ratio, 0.95 [95% CI, 0.78 to 1.17] with nonisolated low HDL-C and 0.81 [95% CI, 0.67-1.00] with isolated low HDL-C). CONCLUSION: Isolated low HDL-C is a novel lipid phenotype that appears to be more prevalent among Asian populations, in whom it is associated with increased coronary risk. Further investigation into this type of dyslipidemia is warranted.

Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial.

BACKGROUND: Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk. METHODS/DESIGN: The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner. DISCUSSION: It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities. Trial registration Current Controlled Trials ISRCTN02839188.

Ischemic stroke in South Asians: a review of the epidemiology, pathophysiology, and ethnicity-related clinical features.

BACKGROUND AND PURPOSE: Within the United Kingdom, mortality from stroke is higher among South Asians compared to European whites. The reasons for this excess cerebrovascular risk in South Asians remain unclear. The aim of this review is to present a comprehensive and systematic overview of the available literature relating to ischemic stroke among South Asian populations identifying distinct features of stroke epidemiology in this group. SUMMARY OF REVIEW: A high frequency of lacunar strokes is a familiar pattern among South Asians, which suggests a greater prevalence of small-vessel disease in South Asians. This may be a consequence of abnormal metabolic and glycemic processes. In addition, stroke mortality among South Asians appears to be explained by glycemic status, which is an independent predictor of long-term stroke mortality. Within India, there is a perceptible rural-urban gradient in stroke prevalence, underlying the dangers of the rapid transition in socioeconomic circumstances seen across the Indian subcontinent. CONCLUSIONS: This review emphasizes the importance of further research into ischemic stroke for South Asians given their higher cardiovascular disease burden and necessity for targeted healthcare approaches.

Glycemic status underlies increased arterial stiffness and impaired endothelial function in migrant South Asian stroke survivors compared to European Caucasians: pathophysiological insights from the West Birmingham Stroke Project.

BACKGROUND: The pathophysiology of an increased risk of cerebrovascular disease mortality among South Asians (SA) remains unclear. Indices of arterial stiffness and endothelial dysfunction are independent markers of vascular disease, having both prognostic and diagnostic implications. We hypothesized that there are ethnic variations in indices of arterial stiffness and endothelial dysfunction between SA and European Caucasian (EC) stroke patients, which may underline a poorer prognosis in the former, and further investigated promoters of vessel wall abnormalities. METHODS: Using a cross-sectional approach, a total of 100 SA stroke survivors were prospectively recruited from the ongoing West Birmingham Stroke Project. Indices of vessel wall characteristics (arterial stiffness and endothelial function [change in reflective index]) were measured noninvasively using the digital volume pulse analysis technique in a temperature-controlled environment, using a direct standardized approach. SA stroke subjects were compared to 60 EC stroke survivors, 60 SA with risk factors, and 73 healthy controls. RESULTS: Among stroke patients, both ethnic groups were comparable for cardiovascular risk profile, except for more diabetes mellitus in SA (P=0.007) subjects and a higher prevalence of atrial fibrillation in EC (P=0.04) subjects. According to the TOAST and Bamford classifications, SA subjects had more small vessel (P=0.04) and lacunar infarctions (P=0.01). SA subjects had higher measurements of arterial stiffness (P<0.001) and impaired endothelial-dependent vascular function (change in reflective index %; P<0.001). On univariate analysis, endothelial function was negatively correlated with fasting plasma glucose (r=-0.4; P<0.001) and total cholesterol level (r=-0.2; P<0.001). On multivariate analysis, glycemic status was independently associated with impaired endothelial function (P=0.008) and increased arterial stiffness (P<0.001) among SA subjects. CONCLUSIONS: SA stroke survivors had more small vessel disease-related cerebrovascular events compared to EC subjects. Underlying glycemic status in SA subjects had an adverse impact on the vascular system, leading to abnormal vessel wall characteristics.

Impact of mean arterial blood pressure on higher arterial stiffness indices in South Asians compared to white Europeans.

BACKGROUND: The pathophysiology of excessive premature coronary heart disease mortality among South Asians living in Britain remains unclear. We hypothesized that higher measures of arterial stiffness among South Asians compared with their white European counterparts would reflect an earlier progression of atherosclerosis, even in the absence of established coronary heart disease risk indices. METHODS: Arterial stiffness was measured by digital volume pulse photoplethysmography in 90 healthy South Asians and compared with 62 matched white Europeans in a temperature-controlled environment using a direct, standardized approach. RESULTS: Both ethnic groups were comparable for coronary heart disease risk profiles and had similar 10-year coronary heart disease risk estimates, but South Asians had a greater mean (SD) stiffness index compared with white Europeans [9.39 (0.22) vs. 8.43 (0.23) m/s; P = 0.007]. On linear regression analysis, mean arterial blood pressure (beta = 0.06; P = 0.03) and age (beta = 0.11; P = 0.002) were independent predictors of arterial stiffness in South Asians. Among white Europeans, age was an independent predictor of arterial stiffness (beta = 0.05; P = 0.01). CONCLUSION: Healthy South Asians have increased systemic arterial stiffness measured by stiffness index compared with white Europeans. There was an adverse and disproportional impact of age and mean arterial pressure on the vascular system in South Asians. Increased indices of arterial stiffness may explain their increased susceptibility to coronary heart disease.

Measurement of stiffness index by digital volume pulse analysis technique: clinical utility in cardiovascular disease risk stratification.

BACKGROUND: Indices of arterial stiffness are accepted as independent markers of cardiovascular disease (CVD), having both positive prognostic and diagnostic implications. The utility of stiffness index (SI) derived from digital volume pulse (DVP) analysis in CVD risk screening is not established. METHODS: Using a representative sample of individuals from local communities (West Midlands, UK), we determined the performance of SI in the discrimination of increasing CVD risk. Arterial stiffness was measured by DVP photoplethysmography (PCA 2; Micro Medical) using a direct, standardized approach. CVD risk assessment was performed in accordance with the Joint British Society guidelines (JBS2). RESULTS: Of our cohort of 247 individuals (51% male; mean age 55.2 (s.d. 10.3) years), 187 were apparently healthy and 60 had established CVD risk factors (diabetes mellitus: 33%, hypertension: 77.8%, hypercholesteremia: 61%). On univariate analysis, SI was strongly associated with CVD risk (the European Society of Cardiology (ESC) based HeartScore) (Pearson correlation coefficient (R): 0.56, P < or = 0.001) and increased in an ordinal fashion from "low risk" to "medium risk" to "high risk" to "very high risk" (pseudo R2 = 0.30; P < 0.001). In receiver operator characteristic curve analysis, SI was the best discriminator between low to medium risk and high-risk categories (area under curve (AUC): 0.76 (95% CI 0.64-0.88), P < 0.001) when compared to total cholesterol, plasma glucose, systolic blood pressure, and waist-to-hip ratio and had the utility to discriminate the individuals with known CVD risk factors such as diabetes and hypertension. CONCLUSION: Noninvasive measurements of arterial stiffness may aid the optimal stratification of CVD risk in an apparently healthy population.

Is soluble CD40 ligand a mediator of angiogenesis in patients with coronary artery disease?

BACKGROUND: In cardiovascular disease, soluble CD40 ligand (sCD40L) has been associated with an adverse prognosis. Angiogenesis has been implicated in the progression of coronary artery disease (CAD) and sCD40L has pro-angiogenic effects in vitro. Angiogenesis itself is regulated by many mediators, such as vascular endothelial growth factor (VEGF) and the angiopoietins (Ang). Ang-1 promotes vascular maturation whilst Ang-2 destabilises the blood vessel and permits vascular growth with VEGF. Hence, selective elevation of VEGF and Ang-2 suggest a state of vascular plasticity and increased angiogenesis. We hypothesised raised plasma levels of VEGF and Ang-2, but not Ang-1, and correlations with raised sCD40L levels and CAD severity/collateralisation in patients with CAD. METHODS: We recruited 153 patients attending diagnostic angiography for CAD and 47 healthy controls. Patients with previous revascularisation or unequivocally normal angiograms were excluded. The coronary atheroma score (CAS) and coronary stenosis score (CSS), and the presence of collaterals, were assessed by 2 blinded observers. Plasma sCD40L, VEGF, Ang-1 and -2 levels were measured by ELISA. RESULTS: Plasma levels of sCD40L, VEGF and Ang-2, but not Ang-1, were higher in CAD patients compared to controls. Both plasma VEGF (r=0.526, p<0.001) and Ang-2 (r=0.429, p<0.001) were correlated with sCD40L, but not with CAS, CSS or collateralisation. On stepwise multivariate regression analysis, plasma sCD40L was an independent predictor of plasma VEGF (p=0.002), and Ang-2 (p<0.001) levels. CONCLUSION: These data suggest abnormal indices of angiogenesis in CAD, which may be associated with increased CD40-CD40L interactions in patients with CAD. Plasma sCD40L, VEGF and Ang-2 levels were not correlated to angiographic CAD/collateralisation.

High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet activation in 880 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors, stroke risk stratification schema, and prognosis.

BACKGROUND AND PURPOSE: There is now considerable evidence that atrial fibrillation is associated with an inflammatory state. We tested the hypothesis that plasma levels of C-reactive protein (CRP; an index of inflammation) and soluble CD40 ligand (an index of platelet activation, with links to inflammation) could be related to 3 established stroke risk stratification schema (SPAF, CHADS(2), and NICE), recognized stroke risk factors or other cardiovascular disease, and prognosis. METHODS: We studied 880 subjects with atrial fibrillation recruited from subjects receiving aspirin 325 mg/d (alone or combined with fixed inefficacious doses of warfarin) from the Stroke Prevention in Atrial Fibrillation (SPAF) III clinical trial. CRP and soluble CD40 ligand were measured by enzyme-linked immunosorbent assay. RESULTS: With respect to the SPAF III stroke risk stratification criteria, those with moderate to high risk had the highest levels of CRP (Kruskal Wallis test, P<0.001), but those with the highest risk had the lowest levels of soluble CD40 ligand (P=0.01). Similarly, CRP levels increased in a positive fashion with increasing stroke risk with respect to the CHADS(2) and NICE risk stratification criteria, whereas soluble CD40 ligand levels were negatively associated with stroke risk. CRP levels were higher among those patients with raised body mass index, diabetes, hypertension, ischemic heart disease, peripheral vascular disease, and recent heart failure, but not those with thromboembolism. Patients were followed-up for a mean time of 453 (standard deviation, 229) days, and all-cause mortality (log rank test, P=0.001), and vascular events (P=0.05), but not stroke, were more common in patients with high CRP levels. Soluble CD40 ligand levels were not related to stroke, vascular events, or all-cause mortality. CONCLUSIONS: Among atrial fibrillation patients, CRP was positively correlated to stroke risk and related to stroke risk factors and prognosis (mortality, vascular events). Soluble CD40 ligand levels were lowest in those at moderate to high risk of stroke and not related to prognosis. The use of CRP in risk stratification for atrial fibrillation merits further study.

Evaluation of B-type natriuretic peptide for validation of a heart failure register in primary care.

BACKGROUND: Diagnosing heart failure and left ventricular systolic dysfunction is difficult on clinical grounds alone. We sought to determine the accuracy of a heart failure register in a single primary care practice, and to examine the usefulness of b-type (or brain) natriuretic peptide (BNP) assay for this purpose. METHODS: A register validation audit in a single general practice in the UK was carried out. Of 217 patients on the heart failure register, 56 of 61 patients who had not been previously investigated underwent 12-lead electrocardiography and echocardiography within the practice site. Plasma was obtained for BNP assay from 45 subjects, and its performance in identifying echocardiographic abnormalities consistent with heart failure was assessed by analysing area under receiver operator characteristic (ROC) curves. RESULTS: 30/217 were found to have no evidence to suggest heart failure on notes review and were probably incorrectly coded. 70/112 who were previously investigated were confirmed to have heart failure. Of those not previously investigated, 24/56 (42.9%) who attended for the study had echocardiographic left ventricular systolic dysfunction. A further 8 (14.3%) had normal systolic function, but had left ventricular hypertrophy or significant valve disease. Overall, echocardiographic features consistent with heart failure were found in only 102/203 (50.2%). BNP was poor at discriminating those with and without systolic dysfunction (area under ROC curve 0.612), and those with and without any significant echocardiographic abnormality (area under ROC curve 0.723). CONCLUSION: In this practice, half of the registered patients did not have significant cardiac dysfunction. On-site echocardiography identifies patients who can be removed from the heart failure register. The use of BNP assay to determine which patients require echocardiography is not supported by these data.

Widening access to cardiovascular healthcare: community screening among ethnic minorities in inner-city Britain - the Healthy Hearts Project.

BACKGROUND: The burden of cardiovascular disease (CVD) in Britain is concentrated in inner-city areas such as Sandwell, which is home to a diverse multi-ethnic population. Current guidance for CVD risk screening is not established, nor are there specific details for ethnic minorities. Given the disparity in equitable healthcare for these groups, we developed a 'tailored' and systematic approach to CVD risk screening within communities of the Sandwell locality. The key anticipated outcomes were the numbers of participants from various ethnic backgrounds attending the health screening events and the prevalence of known and undiagnosed CVD risk within ethnic groups. METHODS: Data was collected during 10 health screening events (September 2005 and July 2006), which included an assessment of raised blood pressure, overweight, hyperlipidaemia, impaired fasting glucose, smoking habit and the 10 year CVD risk score. Specific features of our approach included (i) community involvement, (ii) a clinician who could deliver immediate attention to adverse findings, and (iii) the use of an interpreter. RESULTS: A total of 824 people from the Sandwell were included in this study (47% men, mean age 47.7 years) from community groups such as the Gujarati Indian, Punjabi Indian, European Caucasian, Yemeni, Pakistani and Bangladeshi. A total of 470 (57%) individuals were referred to their General Practitioner with a report of an increased CVD score - undetected high blood pressure in 120 (15%), undetected abnormal blood glucose in 70 (8%), undetected raised total cholesterol in 149 (18%), and CVD risk management review in 131 (16%). CONCLUSION: Using this systematic and targeted approach, there was a clear demand for this service from people of various ethnic backgrounds, of whom, one in two needed review from primary or secondary healthcare. Further work is required to assess the accuracy and clinical benefits of this community health screening approach.

Novel concepts of statin therapy for cardiovascular risk reduction in hypertension.

Hypertension is associated with an increase in cardiovascular events. Pathophysiological mechanisms of this include endothelial damage/dysfunction, inflammatory activation, insulin resistance, platelet activation and alterations in the coagulation cascade leading to a prothrombotic state. Dyslipidaemia acts synergistically with hypertension in increasing cardiovascular risk. HMG CoA reductase inhibitors (statins) are lipid-lowering drugs and more recently have been shown to have a significant pleiotropic effect on endothelial function, inflammation, platelet activation and coagulation. Statins affect the whole pathophysiology of atherogenesis from deposition to plaque rupture and thrombogenesis because of its pleiotropic effects. Therefore it is intuitive that statins may be of benefit in hypertensive patients with conventionally normal lipid levels by preventing the pathological effects of hypertension. There is an increasing clinical evidence base for statins use in patients with hypertension. In this article, the novel pleiotropic and conventional mechanisms of statins, and clinical data of statin therapy in patients with hypertension are reviewed.

Abnormal soluble CD40 ligand and C-reactive protein concentrations in hypertension: relationship to indices of angiogenesis.

BACKGROUND: Abnormal inflammation, platelets and angiogenesis are involved in the pathophysiology of cardiovascular disease (CVD). OBJECTIVE: To test the hypothesis that concentrations of high sensitive C-reactive protein (CRP, an index of inflammation) and soluble CD40 ligand (sCD40L, an index of platelet activation) would be abnormal in hypertension, and in turn, be related to plasma indices of angiogenesis, the angiopoietins-1 and -2, and vascular endothelial growth factor (VEGF), in addition to the presence or absence of CVD. METHODS: Using a cross-sectional approach, we measured plasma concentrations of CRP, sCD40L, VEGF, and angiopoietins-1 and -2 in 147 patients with hypertension (85 with a history of CVD event/s, 62 CVD event-free) and 68 age- and sex-matched healthy controls. RESULTS: Concentrations of sCD40L (P = 0.039), CRP (P < 0.001), angiopoietin-1 (P < 0.001), angiopoietin-2 (P = 0.003) and VEGF (P < 0.001) were all greater amongst hypertensive patients than in controls. There were no significant differences in sCD40L and VEGF concentrations between hypertensive individuals with and without CVD events, but CRP and angiopoietin-1 concentrations were significantly greater amongst those with CVD events. On multiple regression analysis, sCD40L was associated with angiopoietin-2 (P = 0.01) and VEGF (P = 0.007) in hypertensive individuals, but no such associations were found within the healthy control group. CONCLUSION: In patients with hypertension, sCD40L was associated with increased circulating markers of abnormal angiogenesis (angiopoietin-2, VEGF). The interaction between sCD40L and angiogenesis may contribute to the pathophysiology of CVD in hypertension.

Effects of short-term glucocorticoids on hemostatic factors in healthy volunteers.

OBJECTIVE: Increased circulating levels of hemostatic factors have been associated with arterial and venous thrombosis. Although in vitro evidence suggests that glucocorticoids may activate hemostasis and inhibit thrombolysis, no controlled in vivo studies have examined the effects of glucocorticoids on hemostatic factors. We hypothesized that a 5-day treatment course of dexamethasone would increase circulating levels of hemostatic and anti-fibrinolytic factors. METHODS: We randomized 24 healthy men ages 19-39 to receive either dexamethasone 3 mg twice daily versus placebo for 5 days. Parameters examined before and after the intervention included: clotting factors VII, VIII, and XI, von Willebrand factor (vWF), D-dimer, PAI-1, soluble CD40-ligand (sCD40-ligand), and fibrinogen. RESULTS: Dexamethasone tended to modestly increase clotting factors levels and fibrinogen without significantly affecting PAI-1, D-dimer or sCD40-ligand. Factor VII increased by a mean of 13% (p = 0.04 versus placebo), factor VIII by 27% (p = 0.0008), factor XI by 6% (p = 0.01), and fibrinogen by 13% (p = 0.05). CONCLUSIONS: Glucocorticoids may increase the activity of clotting factors in vivo. This may contribute to the reported increased risk of thrombosis in patients with sustained exposure to glucocorticoids.

Role of metabolically active hormones in the insulin resistance associated with short-term glucocorticoid treatment.

BACKGROUND: The mechanisms by which glucocorticoid therapy promotes obesity and insulin resistance are incompletely characterized. Modulations of the metabolically active hormones, tumour necrosis factor alpha (TNF alpha), ghrelin, leptin and adiponectin are all implicated in the development of these cardiovascular risk factors. Little is known about the effects of short-term glucocorticoid treatment on levels of these hormones. RESEARCH METHODS AND PROCEDURES: Using a blinded, placebo-controlled approach, we randomised 25 healthy men (mean (SD) age: 24.2 (5.4) years) to 5 days of treatment with either placebo or oral dexamethasone 3 mg twice daily. Fasting plasma TNFalpha, ghrelin, leptin and adiponectin were measured before and after treatment. RESULTS: Mean changes in all hormones were no different between treatment arms, despite dexamethasone-related increases in body weight, blood pressure, HDL cholesterol and insulin. Changes in calculated indices of insulin sensitivity (HOMA-S, insulin sensitivity index) were strongly related to dexamethasone treatment (p < 0.001). DISCUSSION: Our data do not support a role for TNF alpha, ghrelin, leptin or adiponectin in the insulin resistance associated with short-term glucocorticoid treatment.

Corrigendum to "Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent".

[This corrects the article DOI: 10.1155/2015/924387.].

Tipping the balance: Haemoglobinopathies and the risk of diabetes.

AIM: To establish a link between the risk of diabetes with haemoglobinopathies by examining available evidence of the effects of iron and blood glucose homeostasis from molecular to epidemiological perspectives. METHODS: A systematic literature search was performed using electronic literature databases using various search terms. The International Diabetes Federation World Atlas was used to generate a list of populations with high rates of diabetes. PubMed, Scopus and Google Scholar were used to identify which of these populations also had a reported prevalence of haemoglobin abnormalities. RESULTS: Abnormalities in iron homeostasis leads to increases in reactive oxygen species in the blood. This promotes oxidative stress which contributes to peripheral resistance to insulin in two ways: (1) reduced insulin/insulin receptor interaction; and (2) ß-cell dysfunction. Hepcidin is crucial in terms of maintaining appropriate amounts of iron in the body and is in turn affected by haemoglobinopathies. Hepcidin also has other metabolic effects in places such as the liver but so far the extent of these is not well understood. It does however directly control the levels of serum ferritin. High serum ferritin is found in obese patients and those with diabetes and a meta-analysis of the various studies shows that high serum ferritin does indeed increase diabetes risk. CONCLUSION: From an epidemiological standpoint, it is plausible that the well-documented protective effects of haemoglobinopathies with regard to malaria may have also offered other evolutionary advantages. By contributing to peripheral insulin resistance, haemoglobinopathies may have helped to sculpt the so-called "thrifty genotype", which hypothetically is advantageous in times of famine. The prevalence data however is not extensive enough to provide concrete associations between diabetes and haemoglobinopathies - more precise studies are required.

Effects of short-term glucocorticoids on cardiovascular biomarkers.

CONTEXT: Glucocorticoids are known to acutely increase blood pressure, suppress inflammation, and precipitate insulin resistance. However, the short-term effects of glucocorticoids on other cardiovascular risk factors remain incompletely characterized. OBJECTIVE: Our objective was to determine the effects of a short course of dexamethasone on multiple cardiovascular biomarkers and to determine whether suppression of morning cortisol in response to low-dose dexamethasone is correlated with cardiovascular risk markers in healthy volunteers. DESIGN: We conducted a randomized, double-blind, placebo-controlled study. SETTING: The study took place in a tertiary care hospital. STUDY SUBJECTS: Twenty-five healthy male volunteers, ages 19-39 yr, participated in the study. INTERVENTION: Subjects received either 3 mg dexamethasone twice daily or placebo for 5 d. Subjects also underwent a low-dose (0.5 mg) overnight dexamethasone suppression test. MEASURES: Parameters examined before and after the 5-d intervention included heart rate, blood pressure, weight, fasting lipid variables, homocysteine, renin, aldosterone, insulin resistance (homeostasis model assessment), high-sensitivity C-reactive protein, B-type natriuretic peptide, flow-mediated and nitroglycerin-mediated brachial artery dilatation, and heart rate recovery after exercise. All measurements were done in the morning hours in the fasting state. RESULTS: Dexamethasone increased systolic blood pressure, weight, B-type natriuretic peptide, and high-density-lipoprotein-cholesterol. Dexamethasone decreased resting heart rate, high-sensitivity C-reactive protein, and aldosterone and tended to attenuate nitroglycerin-mediated vasodilatation. There was no effect on flow-mediated vasodilatation, diastolic blood pressure, triglycerides, low-density-lipoprotein-cholesterol, nonesterified fatty acids, homocysteine, or heart rate recovery. The response of circulating cortisol to low-dose dexamethasone had no significant correlation with any of the cardiovascular risk markers. CONCLUSIONS: Short-term glucocorticoids elicits both favorable and unfavorable effects on different cardiovascular risk factors. Manipulation of specific glucocorticoid-responsive physiological pathways deserves further study.

Comparison of brain natriuretic peptide and left ventricular diastolic function determined by tissue Doppler in patients with diabetes mellitus, patients with hypertension without diabetes, and in healthy subjects.

In this study, it was found that increased plasma B-type natriuretic peptide (BNP) levels in patients with diabetes may be related to left ventricular (LV) diastolic relaxation, independent of LV mass and atherosclerosis (using common carotid intima-media thickness as a surrogate index). A "package of care" of glycemic control and cardiovascular risk management was not associated with reduction in BNP levels.

Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease.

Endogenous matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are important mediators of extracellular matrix remodeling, which is integral to plaque progression in coronary artery disease. In addition, high levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. We hypothesized that circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were abnormal in patients who had stable coronary artery disease, and these levels were compared with those in matched controls. We also hypothesized correlations of MMPs, TIMPs, and sCD40L to each other and to high-sensitivity C-reactive protein (a proinflammatory marker), white blood cell count, severity of coronary artery disease (based on angiographic measurements of atherosclerotic burden), and coronary collateralization. We studied 204 adult patients who attended our unit for outpatient diagnostic cardiac catheterization for the investigation of suspected coronary artery disease. Coronary angiograms were scored for atheroma burden and stenosis by 2 independent observers. Circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were measured by enzyme-linked immunosorbent assay. Plasma levels of MMP-9 (p = 0.0099), TIMP-2 (p = 0.0019), and sCD40L (p <0.001), but not TIMP-1 (p = 0.463) were high in patients compared with healthy controls. In patients who had coronary artery disease, MMP-9 and high-sensitivity C-reactive protein levels were significantly higher in women than in men. Only MMP-9 correlated modestly with total white blood cell count (Spearman's correlation, r = 0.274, p = 0.002). Logistic regression of cardiovascular risk factors showed that only white blood cell count was independently associated with MMP-9 (p = 0.02). After standardizing for atheroma and stenosis scores, there were no statistically significant differences in our research indexes in patients who had angiographic collaterals compared with those who did not. In conclusion, stable coronary artery disease is associated with abnormal circulating levels of MMP-9, TIMP-2, and sCD40L, which do not appear to related to each other or to severity of coronary artery disease or collateralization. The gender difference in high-sensitivity C-reactive protein and MMP-9 levels may provide insight into the pathophysiology of coronary artery disease in men and women, and further studies are warranted to explore this potential link.

Efficacy and safety of atorvastatin in South Asian patients with dyslipidemia: an open label noncomparative pilot study.

BACKGROUND: Rates of coronary heart disease (CHD) mortality are 40% higher amongst South Asian men and women living in the UK compared with the general UK population. Despite an established excess CHD risk, little is known of the efficacy and safety of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) amongst South Asian migrants. METHODS AND RESULTS: Hyperlipidemic South Asian patients (raised or uncontrolled low-density lipoprotein cholesterol [LDL-C]) were recruited from two UK centers (n = 33). After a five-week period, which included dietary advice, patients received atorvastatin 10 mg/d for five weeks to achieve a target LDL-C goal of < 3.0 mmol/L, titrated to 20 mg, 40 mg, or 80 mg for a further 12 weeks as required. Significant reductions in LDL-C levels from baseline were observed after 4 weeks' and 17 weeks' treatment with atorvastatin (> or = 33.6%; 26.0, 41.2). Overall, 81% (95% confidence interval [CI]: 62.5, 92.6%) achieved the target LDL-C after 4 weeks' treatment with 10 mg atorvastatin. Titration to a dose of more than 20 mg was required in only one patient (40 mg) at any point during the study. Nineteen patients reported at least one adverse event during the study; the majority were mild in severity and considered unrelated to atorvastatin. CONCLUSIONS: Atorvastatin was effective in achieving target lipid levels and was well tolerated. Statin therapy for high-risk South Asian individuals is likely to benefit CHD outcomes, although further and larger prospective trials are required.