The metabolic syndrome and mortality: the Singapore Cardiovascular Cohort Study

Objective  This study assesses the effect of the metabolic syndrome on all-cause and cardiovascular disease (CVD) mortality in healthy Chinese, Malays and Asian Indians in Singapore. The utility of the metabolic syndrome is also compared with the Framingham risk score for prediction of mortality.
Methods  Healthy participants ( n  = 5699) were grouped by the presence or absence of the metabolic syndrome, and followed up (mean 14·1 years) by data linkage with the National Death Register. Risk of mortality was obtained by Cox's proportional hazards model with adjusted hazard ratios (HRs). Area under receiver operating characteristic (ROC) curves were used to compare the metabolic syndrome and Framingham risk score for prediction of mortality.
Results  During a follow-up of 80 236 person-years, there were 382 deaths, of which 128 were due to CVD. Individuals with the metabolic syndrome had an increased risk of mortality for 'all-causes' (males: HR 1·4, 95% confidence intervals (95%CI) 1·1–1·8; and females: HR 1·8, 95%CI 1·3–2·6). There was also an increased risk of mortality due to CVD (males: HR 3·0, 95%CI 1·9–4·8; and females: HR 2·1, 95%CI 1·1–4·0). The area under ROC for Framingham risk score was higher for both all-cause and CVD mortality than metabolic syndrome.
Conclusions  Although an increased risk of 'all-cause' and CVD mortality due to the metabolic syndrome was found, the Framingham risk function still performed better than the metabolic syndrome in an Asian population. However, the metabolic syndrome should not be disregarded as it is a clinically useful entity for identifying individuals for management of its component CVD risk factors.     

Cardiovascular risk factors and mortality in women

Men and women are subject to similar environmental influences but women have a markedly longer life expectancy, the difference in which is still increasing. In general, the level of saturated fat intake appears the most important determinant of life expectancy and it seems likely that this factor is even responsible for regional differences within a given country. In both men and women in Western populations, serum cholesterol levels are much higher than in Oriental populations. Women have higher total serum cholesterol than men in the age groups below 20 and over 50 years and this discrepancy may play a crucial role in the development of arteriosclerosis. Women also have markedly higher HDL-cholesterol levels than men in Western countries. Other important factors possibly accounting for the difference in life expectancy are the facts that in women less than 50 years of age, blood pressure is lower than in men and in women, smoking is much less prevalent. Overall, however, serum lipid levels and intake of saturated fat have a lesser influence on mortality in women than in men and, accordingly, they are lower predictors of mortality.     

C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men.

BACKGROUND: There is much interest in reported associations between serum C-reactive protein and incident ischaemic heart disease. It is uncertain what this association represents. We aimed to assess the effect of confounding from a number of different sources in the Caerphilly Prospective Heart Disease Study and in particular whether the low grade inflammation indicated by C-reactive protein may be the mechanism whereby non-circulating risk factors may influence pathogenesis of ischaemic heart disease. Methods: Plasma specimens collected during 1979-83 from 1395 men with sufficient sample remaining were assayed for serum C-reactive protein by ELISA. Subsequent mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records and electrocardiographic changes at 5-yearly follow-up examinations. RESULTS: There was a positive association between C-reactive protein and incident ischaemic heart disease (P<0.005) mainly with fatal disease (P<0.002). There was also a positive association with all-cause mortality (P<0.0001). C-reactive protein was significantly associated with a number of non-circulating risk factors including body mass index (P<0.0001), smoking (P<0.0001), low forced expiratory volume in 1 s (P<0.0001), height (P=0.025), low childhood social class (P=0.014) and age (P=0.036). C-reactive protein was also associated positively with circulating risk factors including viscosity, leukocyte count, fibrinogen (all P<0.0001) and insulin (P=0.0058). After adjustment for non-circulating risk factors the association with all-incident ischaemic heart disease and ischaemic heart disease death became non-significant, but the association with all-cause mortality remained (P=0.033). Further adjustment for fibrinogen however removed any hint of an increasing trend in odds for all three outcomes. CONCLUSION: C-reactive protein levels are raised in association with a variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.     

Novel measures of heart rate variability predict cardiovascular mortality in older adults independent of traditional cardiovascular risk factors: the Cardiovascular Health Study (CHS)

Background: It is unknown whether abnormal heart rate turbulence (HRT) and abnormal fractal properties of heart rate variability identify older adults at increased risk of cardiovascular death (CVdth). Methods: Data from 1,172 community‐dwelling adults, ages 72 ± 5 (65–93) years, who participated in the Cardiovascular Health Study (CHS), a study of risk factors for CV disease in people ≥65 years. HRT and the short‐term fractal scaling exponent (DFA1) derived from 24‐hour Holter recordings. HRT categorized as: normal (turbulence slope [TS] and turbulence onset [TO] normal) or abnormal (TS and/or TO abnormal). DFA1 categorized as low (≤1) or high (>1). Cox regression analyses stratified by Framingham Risk Score (FRS) strata (low = <10, mid = 10–20, and high >20) and adjusted for prevalent clinical cardiovascular disease (CVD), diabetes, and quartiles of ventricular premature beat counts (VPCs). Results: CVdths (N = 172) occurred over a median follow‐up of 12.3 years. Within each FRS stratum, low DFA1 + abnormal HRT predicted risk of CVdth (RR = 7.7 for low FRS; 3.6, mid FRS; 2.8, high FRS). Among high FRS stratum participants, low DFA1 alone also predicted CVdth (RR = 2.0). VPCs in the highest quartile predicted CVdth, but only in the high FRS group. Clinical CV disease predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9, high). Diabetes predicted CVdth in the highest FRS group only (RR = 2.2). Conclusions: The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth among older adults even after adjustment for conventional CVD risk measures and the presence of CVD.     

Hypertension, endothelial dysfunction and cardiovascular risk

Increased blood pressure induces functional and structural changes of the vascular endothelium. Depression of endothelium-dependant vasodilatation is an early manifestation of endothelial dysfunction due to hypertension. It can be demonstrated by pharmacological or physiological tests. Decreased availability of nitric oxide (NO) is a major determinant of the depression of vasodilatation. It may be caused by a reduction in the activity of NO-endothelial synthase (NOSe) related to: 1) a deficit in substrate (L-arginine), 2) an inhibition by asymmetrical dimethylarginine, 3) a deficit in the cofactor tetrahydrobiopterin (BH4). However, the increase in oxidative stress, a producer of superoxide radicals which combine with NO to form peroxynitrates (ONOO-), is the determining factor. It is related to activation of membranous NAD(P)H oxidases initiated by the stimulation of activating mecanosensors of protein C kinase. The message is amplified by oxidation of BH4 which transforms the NOSe into a producer of superoxide radicals. A cascade of auto-amplification loops leading to atherosclerosis and its complications is then triggered. The superoxide radicals and the peroxynitrates oxidise the LDL-cholesterol. They activate the nuclear factor-kappaB which controls the genes stimulating the expression of many proteins: angiotensinogen and AT1 receptors which stimulate the sympathetic system, receptors of oxidised LDL, adhesion and migration factors (ICAM-1, VCAM-1, E-selectin and MCP-1), pro-inflammatory cytokins (interleukines and TNF-alpha), growth factors (MAP kinases), plasminogen activator inhibitor 1. The monocytes and smooth muscle cells produce metalloproteinases and pro-inflammatory cytokins which destabilise the atheromatous plaque and favourise vascular remodelling. Inshort, the endothelial dysfunction due to hypertension plays a role in a complex physiopathological process and is a marker of future cardiovascular events.     

Cardiovascular mortality in overweight subjects: the key role of associated risk factors

The role of obesity and overweight as independent risk factors for cardiovascular disease is still debated. The aim of this study was to evaluate the impact of overweight on cardiovascular mortality according to the presence or absence of associated risk factors. This study included 139,562 men and 104,236 women, aged 18 to 95 years, who had a standard health checkup at the IPC Center between 1972 and 1988. The follow-up period for mortality ended in December 1997. In both genders, the prevalence of hypertension, diabetes, and hypercholesterolemia increased with body mass index (P<0.001). When compared with subjects with a body mass index <25 kg/m2 without associated risk factors, overweight subjects without associated risk factors did not have an increased risk of cardiovascular mortality. Risk of cardiovascular death increased significantly when overweight was associated with hypertension alone [hazard ratio: 2.05 (1.71 to 2.46) in men; 2.15 (1.48 to 3.11) in women]. In both genders, the association of overweight with diabetes alone or hypercholesterolemia alone did not increase the risk. By contrast, in the presence of hypertension, cardiovascular mortality dramatically increased in overweight subjects with hypercholesterolemia [hazard ratio: 2.65 (2.20 to 3.19) in men, 2.57 (1.80 to 3.68) in women] or diabetes [hazard ratio: 3.01 (2.29 to 3.95) in men; 4.50 (2.67 to 7.58) in women]. The data suggest that the presence of high blood pressure in overweight subjects is the key factor leading to a significant increase in cardiovascular mortality. Because overweight significantly increases the prevalence of associated risk factors, especially hypertension, it should be considered as a major cardiovascular risk determinant.     

Impact of sex-specific body composition on cardiovascular risk factors: the Hong Kong Cardiovascular Risk Factor Study

The aim of the study was to analyze the effects of sex-specific distribution of adiposity, particularly emphasizing the independent contribution of waist and hip circumferences relative to body mass index (BMI), on cardiovascular risk factors in a Chinese population. Blood pressure and anthropometric and biochemical parameters were measured in 2510 population-based Chinese subjects. The relative contributions of waist and hip circumferences to the presence of cardiovascular risk factors were determined. The Chinese men were significantly larger than women, with greater BMI and central adiposity. Waist and hip circumferences were both positively associated with the presence of hypertension, dyslipidemia, and diabetes. However, after adjustment for BMI and age, hip circumference exhibited a significant dose-dependent inverse relationship with dyslipidemia and diabetes in women, but not men. Sex-specific differences exist. After adjustment for age and BMI, hip circumferences independently and inversely contribute to cardiovascular risk in women, but not in men. Increasing adjusted waist circumference was associated with increased risk of hypertension and diabetes in Chinese and dyslipidemia in women only.     

Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study

OBJECTIVE: Metabolic changes caused by antiretroviral therapy (ART) may increase the risk of coronary heart disease (CHD). We evaluated changes in the prevalence of cardiovascular risk factors (CVRFs) and 10-year risk of CHD in a large cohort of HIV-infected individuals. METHODS: All individuals from the Swiss HIV Cohort Study (SHCS) who completed at least one CVRF questionnaire and for whom laboratory data were available for the period February 2000 to February 2006 were included in the analysis. The presence of a risk factor was determined using cut-offs based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), the American Diabetes Association, and the Swiss Society for Cardiology. RESULTS: Overall, 8,033 individuals completed at least one CVRF questionnaire. The most common CVRFs in the first completed questionnaire were smoking (57.0%), low high-density lipoprotein (HDL) cholesterol (37.2%), high triglycerides (35.7%), and high blood pressure (26.1%). In total, 2.7 and 13.8% of patients were categorized as being at high (>20%) and moderate (10-20%) 10-year risk for CHD, respectively. Over 6 years the percentage of smokers decreased from 61.4 to 47.6% and the percentage of individuals with total cholesterol >6.2 mmol/L decreased from 21.1 to 12.3%. The prevalence of CVRFs and CHD risk was higher in patients currently on ART than in either pretreated or ART-naive patients. CONCLUSION: During the 6-year observation period, the prevalence of CVRFs remains high in the SHCS. Time trends indicate a decrease in the percentage of smokers and individuals with high cholesterol.     

C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly

Serum C-reactive protein (CRP) reflects inflammation and predicts cardiovascular disease in middle-aged individuals. We investigated CRP, risk factors, and 10-year mortality in 3 elderly cohorts (aged 75, 80, and 85 years; n=455) of the population-based Helsinki Ageing Study. Clinical and laboratory examinations were performed at baseline, and in 1998, CRP was measured by a sensitive method (sensitivity 0.3 mg/L) from frozen serum samples. Mortality data were retrieved from national registers. Serum CRP ranged from 0.18 to 170.0 mg/L (interquartile range 0.68 to 4.10 mg/L, median 1.60 mg/L). CRP correlated significantly with body mass index and plasma insulin and was associated with smoking at baseline. An inverse correlation was found with albumin and total and HDL cholesterol. CRP was not associated with diabetes or cardiovascular disease but was significantly (P=0.015) higher in persons with (n=70) than without (n=385) dementia. During the 10-year follow-up, 61% (n=278) of the cohort died; half of the deaths were due to cardiovascular diseases. Mean CRP in survivors and nonsurvivors was 3.16 and 5.22 mg/L (P=0.017), respectively. After controlling for age and sex, baseline CRP (per 10 mg/L) significantly predicted the 10-year total mortality (risk ratio 1.20, 95% CI 1.08 to 1.32) and cardiovascular mortality (risk ratio 1.22, 95% CI 1.10 to 1.35). Predictive value was found in the 75-year-old cohort, but it was clearly attenuated in the 80- and 85-year-old cohorts. The results indicate that CRP is associated with several cardiovascular risk factors in the elderly. CRP alone predicts overall and cardiovascular mortality, but the prediction was significant in only the 75-year-old cohort.