Weber M, McNicoll S, Marcil M, Connelly P, Lussier-Cacan S, Davignon J, Latour Y, Genest J
Cardiovascular Genetics Laboratory, Clinical Research Institute of Montreal, Quebec.
Can J Cardiol. 1997 Mar;13(3):253-60.
Plasma lipoprotein cholesterol abnormalities, diabetes, hypertension and smoking have all been identified as independent predictors of cardiovascular events. Clustering of multiple risk factors suggests a common metabolic link among high blood pressure, insulin resistance, plasma lipoprotein abnormalities and obesity. New guidelines for the management of dyslipidemias target patients with established coronary artery disease (CAD), and high risk patients with multiple risk factors and severe genetic lipoprotein disorders, such as familial hypercholesterolemia. To determine the prevalence of lipoprotein, apolipoprotein and metabolic disorders in premature CAD, 243 men and 61 women with premature CAD (occurring before age 60 years) and 203 age- and sex-matched controls (152 men, 61 women) were studied. After correcting for beta-blocker use (40% of men and 54% of women), hypertension and diabetes were seen more frequently in CAD patients than in controls. In men and women, cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein (a) were significantly higher, and high density lipoprotein (HDL) cholesterol was lower, in CAD patients than in controls. By stratifying patients according to LDL cholesterol: HDL cholesterol ratio (5 or less, or greater than 5) and by triglyceride levels (less than 2.3 mmol/L, or 2.3 mmol/L or greater), significantly more men and women with CAD were found to have an elevated LDL cholesterol:HDL cholesterol ratio and elevated triglycerides (13.8% versus 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 presence of hypertension, lipoprotein abnormalities, diabetes or fasting blood glucose above 7.0 mmol/L, and a body mass index of 27 or greater. The prevalence of a metabolic factor index of 3 or more was 29.2% in CAD men versus 6.7% in controls (P < 0.0001) and 38.3% in CAD women versus 11.7% in controls (P < 0.01). Familial hypercholesterolemia was seen in fewer than 5% of patients with premature CAD and type III dyslipoproteinemia in one of 343 CAD patients. The distribution of apolipoprotein E phenotypes was the same in CAD patients and controls. Multivariate analysis revealed that in men, HDL cholesterol, lipoprotein (a) levels and smoking were the best predictors of risk. In men, plasma levels of LDL cholesterol, triglycerides or body mass index did not enter the model at the P < 0.05 level. In women, low HDL cholesterol, lipoprotein (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 population, HDL and lipoprotein (a) are the best metabolic markers of premature CAD; metabolic factor clustering is common in patients with premature CAD.
血浆脂蛋白胆固醇异常、糖尿病、高血压和吸烟均已被确定为心血管事件的独立预测因素。多种危险因素的聚集表明高血压、胰岛素抵抗、血浆脂蛋白异常和肥胖之间存在共同的代谢联系。血脂异常管理的新指南针对已确诊冠心病（CAD）的患者，以及具有多种危险因素和严重遗传性脂蛋白疾病（如家族性高胆固醇血症）的高危患者。为了确定早发CAD患者中脂蛋白、载脂蛋白和代谢紊乱的患病率，对243名男性和61名女性早发CAD患者（发病年龄在60岁之前）以及203名年龄和性别匹配的对照者（152名男性，61名女性）进行了研究。在校正β受体阻滞剂的使用情况（男性40%，女性54%）后，CAD患者中高血压和糖尿病的发生率高于对照组。在男性和女性中，CAD患者的胆固醇、甘油三酯、低密度脂蛋白（LDL）胆固醇、载脂蛋白B和脂蛋白（a）显著高于对照组，而高密度脂蛋白（HDL）胆固醇则低于对照组。根据LDL胆固醇：HDL胆固醇比值（5或更低，或大于5）以及甘油三酯水平（低于2.3 mmol/L，或2.3 mmol/L或更高）对患者进行分层，发现CAD男性和女性中LDL胆固醇：HDL胆固醇比值升高和甘油三酯升高的比例明显更高（CAD组与对照组合并，男性和女性，13.8%对1.9%，P<0.0001）。设计了一个代谢因子指数，高血压、脂蛋白异常、糖尿病或空腹血糖高于7.0 mmol/L以及体重指数为27或更高各计1分。代谢因子指数为3或更高的患病率在CAD男性中为29.2%，对照组为6.7%（P<0.0001），在CAD女性中为38.3%，对照组为11.7%（P<0.01）。早发CAD患者中家族性高胆固醇血症的发生率不到5%，343名CAD患者中有1名患有III型血脂蛋白异常。CAD患者和对照组的载脂蛋白E表型分布相同。多变量分析显示，在男性中，HDL胆固醇、脂蛋白（a）水平和吸烟是风险的最佳预测因素。在男性中，LDL胆固醇、甘油三酯的血浆水平或体重指数在P<0.05水平时未进入模型。在女性中，低HDL胆固醇、脂蛋白（a）、糖尿病的存在、吸烟和载脂蛋白B水平都是风险的预测因素（P<0.05）。然而，危险因素的聚集可能是风险的最佳预测因素。在这个选定的人群中，HDL和脂蛋白（a）是早发CAD的最佳代谢标志物；代谢因子聚集在早发CAD患者中很常见。
