Effects of Nonlipid Risk Factors on Atherosclerosis in Youth With a Favorable Lipoprotein Profile

TLDR

Although dyslipoproteinemia is strongly linked to coronary heart disease, the impact of nonlipid risk factors such as smoking, hypertension, obesity, diabetes, and impaired glucose tolerance has been underappreciated, especially when lipoprotein profiles are favorable. The PDAY multicenter study evaluated how nonlipid risk factors influence atherosclerosis in 856 young adults (15–34 y) with favorable lipoprotein profiles who died of external causes. Even with favorable lipoprotein levels, smokers, hypertensive blacks, obese men, and those with impaired glucose tolerance exhibited significantly greater atherosclerotic lesions in the abdominal aorta and coronary arteries, with obese men showing the most severe LAD lesions.

Abstract

Background —The strong association between coronary heart disease and dyslipoproteinemia has often overshadowed the effects of the nonlipid risk factors–smoking, hypertension, obesity, and diabetes and impaired glucose tolerance–and even led to questioning the importance of these risk factors in the presence of a favorable lipoprotein profile. Methods and Results —A cooperative multicenter study, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY), examined the relation of the nonlipid risk factors to atherosclerosis in 629 men and 227 women 15 to 34 years of age who died of external causes and who had a favorable lipoprotein profile (non-HDL cholesterol <4.14 mmol/L [<160 mg/dL] and HDL cholesterol ≥0.91 mmol/L [≥35 mg/dL]). In the abdominal aorta, smokers had more extensive fatty streaks and raised lesions than nonsmokers, and hypertensive blacks had more raised lesions than normotensive blacks. In the right coronary artery, hypertensive blacks had more raised lesions than normotensive blacks, obese men (body mass index ≥30 kg/m 2 ) had more extensive fatty streaks and raised lesions than nonobese men, and individuals with impaired glucose intolerance had more extensive fatty streaks. Obese men had more severe lesions (American Heart Association grade 2 through 5) of the left anterior descending coronary artery. Conclusions —These substantial effects of the nonlipid risk factors on the extent and severity of coronary and aortic atherosclerosis, even in the presence of a favorable lipoprotein profile, support the need to control all cardiovascular risk factors.