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Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population-based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixedeffects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11-1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavorable risk factor burden. [ABSTRACT FROM AUTHOR]

Carotid intima-media thickness (CIMT) is a marker of cardiovascular risk. It is unclear whether measurement of mean common CIMT improves 10-year risk prediction of first-time myocardial infarction or stroke in individuals with elevated blood pressure. We performed an analysis among individuals with elevated blood pressure (ie, a systolic blood pressure ≥ 140 mmHg and a diastolic blood pressure ≥ 90 mmHg) in USE-IMT, a large ongoing individual participant data meta-analysis. We refitted the risk factors of the Framingham Risk Score on asymptomatic individuals (baseline model) and expanded this model with mean common CIMT (CIMT model) measurements. From both models, 10-year risks to develop a myocardial infarction or stroke were estimated. In individuals with elevated blood pressure, we compared discrimination and calibration of the 2 models and calculated the net reclassification improvement (NRI). We included 17 254 individuals with elevated blood pressure from 16 studies. During a median follow-up of 9.9 years, 2014 first-time myocardial infarctions or strokes occurred. The C-statistics of the baseline and CIMT models were similar (0.73). NRI with the addition of mean common CIMT was small and not significant (1.4%; 95% confidence intervals, -1.1 to 3.7). In those at intermediate risk (n=5008, 10-year absolute risk of 10% to 20%), the NRI was 5.6% (95% confidence intervals, 1.6-10.4). There is no added value of measurement of mean common CIMT in individuals with elevated blood pressure for improving cardiovascular risk prediction. For those at intermediate risk, the addition of mean common CIMT to an existing cardiovascular risk score is small but statistically significant. [ABSTRACT FROM AUTHOR]

Background: Both high insulin resistance and low insulin secretion are the causes of diabetes mellitus. Japanese level of insulin secretion said to be lower than Western people. However, the association between insulin resistance, secretion and risk of coronary heart disease (CHD) or stroke in non-diabetic population remains unknown. Hypothesis: We assessed the hypothesis that each higher insulin resistance and lower insulin secretion is associated with increased risk of CHD even in nondiabetic population. Methods: A prospective study of Japanese subjects aged 40-79 years was undertaken using data collected from 5,639 participants (1,971 men and 3,668 women) who had no past history of cardiovascular disease or diabetes mellitus in cardiovascular risk surveys conducted in three communities of the Circulatory Risk in Communities Study (CIRCS) in 2000 and 2001. Insulin resistance was calculated on the basis of fasting glucose (mg/dL) and insulin levels (µU/mL) according to the homeostasis model assessment (HOMA-r) method: glucose x insulin / 405. The HOMA-beta cell function (HOMA-b) was calculated by using the following formula: 360 x fasting insulin (µU/mL) / (fasting glucose (mg/dL) - 63). Each incidence of CHD and stroke was ascertained by systematic surveillance. The hazard ratios (HRs) of incidence of CHD and 95% confidence intervals (CI) associated with a 1 standard deviation (SD) increase in log(HOMA-r) and in log(HOMA-b) were calculated with adjustment for age and other potential confounding factors using the Cox proportional hazards model. Results: During an average follow up of 9.8-years, 39 incident CHD (including 23 myocardial infarction) and 123 incident stroke occurred. Higher insulin resistance tended to increase risk of CHD or myocardial infarction, but all HRs did not reach statistical significance. The multivariable HRs in log(HOMA-r) for risk of CHD were 1.30(95% CI: 0.23 to 7.42) for men, 2.84(0.60 to 13.56) for women, and 1.56(0.40 to 6.04) for total subjects. The corresponding HRs of myocardial infarction were 3.73(0.31 to 44.87) for men, 2.45(0.46 to 12.98) for women, and 2.71(0.48 to 15.36) for total subjects. Lower insulin secretion associated with risk of CHD or myocardial infarction, and some of HRs reached statistical significance. The multivariable HRs in log(HOMA-b) for risk of CHD were 1.17(0.56 to 2.45) for men, 0.31(0.10 to0.96, p=0.042) for women, and 0.75(0.40 to1.42) for total subjects. The corresponding HRs of myocardial infarction were 0.53(0.18 to1.53) for men, 0.31(0.07 to 1.35) for women, and 0.42(0.18 to1.00, p=0.049) for total subjects. There was no interaction between HOMA-r and HOMA-b. HOMA-r and HOMA-b did not associated with incidence of stroke. Conclusions: Lower insulin secretion may be associated with increased risk of coronary heart disease among non-diabetic Japanese population. [ABSTRACT FROM AUTHOR]