Cardiovascular Risk Factors Associated With Insulin Resistance Cluster in Families With Early-Onset Coronary Heart Disease

Abstract

Abstract-Coronary heart disease (CHD) is a multifactorial disease caused by environmental and genetic factors. CHD clusters in families, but it is not known whether susceptibility to early-onset CHD is associated with the clustering of cardiovascular risk factors. Therefore, we determined the levels of cardiovascular risk factors among siblings with and without severe early-onset CHD drawn from 101 Finnish families. Probands with CHD, compared with their siblings without CHD, had, respectively, higher 2-hour insulin levels (475. Key Words: risk factors Ⅲ coronary disease Ⅲ insulin resistance C oronary heart disease (CHD) is a multifactorial disease having environmental and genetic components. Smoking, elevated blood pressure, and high cholesterol levels are classic risk factors for CHD, but they explain, at most, 50% of the risk for CHD. 1,2 Also, diabetes, hyperinsulinemia, low HDL cholesterol level, hypertriglyceridemia, obesity, central obesity, and physical inactivity increase the risk for CHD. 3 Several previous prospective 4,5 and cross-sectional 6,7 studies have demonstrated that CHD clusters in families, and genetic factors have been suggested to explain almost 50% of the risk for CHD in individuals aged Ͻ60 years. 8 Although several candidate genes and environmental factors have been proposed to explain accelerated atherosclerosis, the mechanisms behind the familial clustering of CHD have remained unexplained. 9 Two possibilities have to be considered. First, early-onset CHD could be due to environmental or genetic factors independent of adverse changes in known cardiovascular risk factors. Second, adverse changes in known cardiovascular risk factors, eg, dyslipidemia, 10 elevated blood pressure, 11 obesity, 12 and diabetes, 6 aggregating in families with early-onset CHD and caused by environmental or genetic factors could explain the excess of atherosclerosis.To investigate these 2 possibilities, we determined the levels of cardiovascular risk factors among affected and unaffected siblings from families with premature CHD to evaluate whether the clustering of early-onset CHD in families could be explained by the aggregation of adverse changes in known cardiovascular risk factors. Methods SubjectsAll subjects participating in the present study were Finnish and living in Eastern Finland. Since 1983, the Kuopio University Hospital has been responsible for Ͼ90% of coronary angiographies performed in Eastern Finland (North Savo, North Karelia, Mikkeli, and Savonlinna Central Hospital districts). Probands who had severe CHD at an early age were identified from the coronary angiogram register of the Kuopio University Hospital. The formation of the study population is described in Figure 1. CHD was considered to be early if men were aged Յ55 years and women were aged Յ65 years at the time of diagnosis. 13,14 The criteria for severe CHD were stenoses Ͼ50% in coronary angiography in at least 2 main coronary arteries. Until September 1997, 6395 persons had undergone angiography in the Kuopio University Hospital, ...

Interaction of Body Mass Index and Framingham Risk Score in Predicting Incident Coronary Disease in Families

“…[33][34][35][36] In a study of Finnish families with premature CHD, the clustering of risk factors associated with insulin resistance was more common in siblings who developed early-onset CHD compared with those who did not. 37 Excess adiposity is also associated with atherogenic lipoprotein profiles (elevated triglycerides and low HDL cholesterol), although our study findings suggest that BMI predicts increased CHD risk independent of atherogenic remnant-rich lipoproteins. 38 Interestingly, the relationship between the degree of obesity and the extent of metabolic abnormalities is heterogeneous, with largely unknown environmental, genetic, and geneenvironment interactions that may potentially modify the effects of obesity on CHD risk.…”

Relationship between serum osteocalcin levels and carotid intima-media thickness in Chinese postmenopausal women

“…27<29 These metabolism-related factors have been confirmed to affect the onset and progression of atherosclerosis. 30,31 Therefore, we inferred that the indirect effects of osteocalcin on atherosclerosis pathogenesis can contribute to the beneficial role of osteocalcin in mediating atherosclerosis-related risk factors. On the other hand, serum osteocalcin might directly exert a protective effect on atherosclerosis.…”

Metabolic syndrome: an appraisal of the pro-inflammatory and procoagulant status

“…Among siblings from Eastern Finland with characteristics of the metabolic syndrome, fibrinogen levels were significantly higher (3.9 AE 0.1 g/L versus 3.4 AE 0.1 g/L; P = 0.008) in siblings with early-onset CHD ( 55 years in men and 65 years in women) compared with their siblings without CHD [98]. In ECAT, there was a weak correlation (r = 0.14, P \ 0.0001) between insulin levels and fibrinogen; however, this association was substantially reduced (r = 0.05, P = 0.07) by simultaneous adjustment for other markers of inflammation, including CRP and the white cell count [99].…”