High glycaemic variables, especially 2-h post-load glucose concentrations and to a lesser extent HbA1c values, indicate a risk of all-cause and cardiovascular mortality in a general population without known diabetes.

Background-Our purposes were to estimate the strength of the longitudinal relationship between hyperinsulinemia and cardiovascular diseases (CVD) from the available literature and to identify study characteristics that modify this relationship. Methods and Results-Articles were identified by means of a MEDLINE and Embase search and citation tracking. Eligible studies were prospective population-based cohort studies and nested case-control studies on the relationship between, on the one hand, fasting or nonfasting insulin levels and, on the other hand, myocardial infarction, death from coronary heart disease, and/or ECG abnormalities. Data were extracted pertaining to insulin measurements, type of outcome studied, adjustment for confounding, sex, mean age of the study population, follow-up period, insulin assay, and ethnic background (white or nonwhite). Associations of insulin and CVD were reexpressed in a uniform manner, an estimate of relative risk (RR) and 95% CI, to be used in meta-regression analyses. Twelve of 17 potentially eligible articles provided sufficient information. Overall, a weak positive association was found. The meta-analysis resulted in an estimated summary RR (95% CI) of 1.18 (1.08 to 1.29) for differences in insulin level, equivalent to the difference between the 75th and the 25th percentiles of the general population in the Netherlands. Ethnic background and type of insulin assay modified the relationship between insulin and CVD with borderline significance. Conclusions-Hyperinsulinemia is a weak risk indicator for the occurrence of CVD. The relationship between hyperinsulinemia and CVD was modified by ethnic background and by the type of insulin assay involved. (Circulation. 1998;97:996-1001.)

Objectives: Patients with rheumatoid arthritis (RA) have an increased cardiovascular risk, but the magnitude of this risk is not known precisely. A study was undertaken to investigate the associations between RA and type 2 diabetes (DM2), a well-established cardiovascular risk factor, on the one hand, and cardiovascular disease (CVD) on the other. Methods: The prevalence of CVD (coronary, cerebral and peripheral arterial disease) was determined in 353 randomly selected outpatients with RA (diagnosed between 1989 and 2001, aged 50-75 years; the CARRÉ study) and in participants of a population-based cohort study on diabetes and CVD (the Hoorn study). Patients with RA with normal fasting glucose levels from the CARRÉ study (RA, n = 294) were compared with individuals from the Hoorn study with normal glucose metabolism (non-diabetic, n = 258) and individuals with DM2 (DM2, n = 194). Results: The prevalence of CVD was 5.0% (95% CI 2.3% to 7.7%) in the non-diabetic group, 12.4% (95% CI 7.5% to 17.3%) in the DM2 group and 12.9% (95% CI 8.8% to 17.0%) in those with RA. With non-diabetic individuals as the reference category, the age-and gender-adjusted prevalence odds ratio (OR) for CVD was 2.3 (95% CI 1.1 to 4.7) for individuals with DM2 and 3.1 (95% CI 1.6 to 6.1) for those with RA. There was an attenuation of the prevalences after adjustment for conventional cardiovascular risk factors (OR 2.0 (95% CI 0.9 to 4.5) and 2.7 (95% CI 1.2 to 5.9), respectively). Conclusions: The prevalence of CVD in RA is increased to an extent that is at least comparable to that of DM2. This should have implications for primary cardiovascular prevention strategies in RA.

This study will evaluate the importance of insulin resistance in the development of CVD and diabetes, and has implications for the development of prevention and treatment strategies.

Decreased heart rate variability has been associated with an adverse prognosis in patients after myocardial infarction. Studies carried out in the population at large show contradictory results. The authors examined the association between heart rate variability on a standard 10-second electrocardiogram and cardiac and all-cause mortality in the Rotterdam Study, a population-based cohort study of men and women aged > or =55 years, using data collected between 1990 and 1996 (mean follow-up = 4 years). Heart rate variability, taken as the standard deviation of normal R-R intervals (SDNN), was computed by means of the Modular ECG Analysis System. After exclusion of subjects with arrhythmia and those with fewer than six normal R-R intervals, the study population consisted of 2,088 men and 3,184 women. Cox's proportional hazards model was used to examine the age- and sex-adjusted risk for cardiac, noncardiac, and total mortality in relation to quartiles of SDNN, using the third quartile of SDNN as the reference category. Subjects in the lowest quartile of SDNN relative to those in the third quartile had an 80 percent age- and sex-adjusted increased risk for cardiac mortality (hazard ratio = 1.8; 95% confidence interval: 1.0, 3.2). Interestingly, for subjects in the highest quartile of SDNN, an even more pronounced risk for cardiac mortality was present (hazard ratio = 2.3; 95% confidence interval: 1.3, 4.0). Additional adjustment for possible confounders did not materially change the risk estimates. The authors conclude that heart rate variability measured on the standard 10-second electrocardiogram can be used to identify older men and women with an increased risk for cardiac mortality. In the elderly, increased heart rate variability is an even stronger indicator of cardiac mortality than decreased heart rate variability. Further studies are needed to confirm these findings and to elucidate their physiologic meaning.

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OBJECTIVELow-grade chronic inflammation has been hypothesized to underlie the constellation of cardiometabolic risk factors, possibly by inducing insulin resistance. In the present study, we investigated associations between inflammation markers, insulin sensitivity (expressed as the ratio of the M value to the mean plasma insulin concentrations measured during the final 40 min of the clamp [M/I]), and a range of cardiometabolic risk factors in a large, healthy population.RESEARCH DESIGN AND METHODSThe Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort includes 1,326 nondiabetic European men and women, aged between 30 and 60 years. We measured cardiometabolic risk factors and performed a hyperinsulinemic-euglycemic clamp. We determined total white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) as markers of chronic inflammation.RESULTSWBC and ESR were both strongly associated with M/I. WBC and ESR were further associated with a range of cardiometabolic risk factors. Associations between WBC and HDL cholesterol, triglycerides, heart rate, fasting C-peptide, and insulin and 2-h insulin in men and women and between WBC and 2-h glucose in women remained significant after adjustment for both M/I and waist circumference. Associations between ESR and HDL cholesterol, heart rate, fasting, and 2-h insulin in men and women and between ESR and fat mass in women remained significant after adjustment for M/I and waist circumference.CONCLUSIONSThis study showed that low-grade chronic inflammation is associated with the cardiometabolic risk profile of a healthy population. Insulin resistance, although strongly associated with inflammation, does not seem to play a large intermediary role.

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