METABOLIC FACTORS CLUSTERING, LIPOPROTEIN CHOLESTEROL, APOLIPOPROTEIN-B, LIPOPROTEIN (A) AND APOLIPOPROTEIN-E PHENOTYPES IN PREMATURE CORONARY-ARTERY DISEASE IN FRENCH-CANADIANS

Plasma lipoprotein cholesterol abnormalities, diabetes, hypertension a nd smoking have all been identified as independent predictors of cardi ovascular events. Clustering of multiple risk factors suggests a commo n metabolic link among high blood pressure, insulin resistance, plasma lipoprotein abnormalities and obesity. New guidelines for the managem ent of dyslipidemias target patients with established coronary artery disease (CAD), and high risk patients with multiple risk factors and s evere genetic lipoprotein disorders, such as familial hypercholesterol emia. To determine the prevalence of lipoprotein, apolipoprotein and m etabolic disorders in premature CAD, 243 men and 61 women with prematu re CAD (occurring before age 60 years) and 203 age- and sex-matched co ntrols (152 men, 61 women) were studied. After correcting for beta-blo cker use (40% of men and 54% of women), hypertension and diabetes were seen more frequently in CAD patients than in controls. In men and wom en, cholesterol, triglycerides, low density lipoprotein (LDL) choleste rol, apolipoprotein B and lipoprotein (a) were significantly higher, a nd high density lipoprotein (HDL) cholesterol was lower, in CAD patien ts than in controls. By stratifying patients according to LDL choleste rol:HDL cholesterol ratio (5 or less, or greater than 5) and by trigly ceride levels (less than 2.3 mmol/L, or 2.3 mmol/L or greater), signif icantly more men and women with CAD were found to have an elevated LDL cholesterol:HDL cholesterol ratio and elevated triglycerides (13.8% v ersus 1.9%, men and women combined, CAD versus controls, P<0.0001). A metabolic factor index was devised, assigning a score of 1 each for pr esence of hypertension, lipoprotein abnormalities, diabetes or fasting blood glucose above 7.0 mmol/L, and a body mass index of 27 or greate r. The prevalence of a metabolic factor index of 3 or more was 29.2% i n CAD men versus 6.7% in controls (P<0.0001) and 38.3% in CAD women ve rsus 11.7% in controls (P<0.01). Familial hypercholesterolemia was see n in fewer than 5% of patients with premature CAD and type III dyslipo proteinemia in one of 343 CAD patients. The distribution of apolipopro tein E phenotypes was the same in CAD patients and controls. Multivari ate analysis revealed that in men, HDL cholesterol, lipoprotein (a) le vels and smoking were the best predictors of risk. In men, plasma leve ls of LDL cholesterol, triglycerides or body mass index did not enter the model at the P<0.05 level. In women, low HDL cholesterol, lipoprot ein (a), the presence of diabetes, smoking and apolipoprotein B levels were all predictors of risk (P<0.05). However, the clustering of risk factors may be the best predictor of risk. In this selected populatio n, HDL and lipoprotein (a) are the best metabolic markers of premature CAD; metabolic factor clustering is common in patients with premature CAD.