Hautanen A, Mänttäri M, Manninen V, Tenkanen L, Huttunen J K, Frick M H, Adlercreutz H
Department of Clinical Chemistry, University of Helsinki, Finland.
Atherosclerosis. 1994 Feb;105(2):191-200. doi: 10.1016/0021-9150(94)90049-3.
We investigated the role of adrenal androgens, cortisol, testosterone and sex-hormone binding globulin (SHBG) as coronary risk factors using a nested case-control design. The study population consisted of 62 cases with cardiac end-points and 97 controls on placebo during the last 4 years in the Helsinki Heart Study. Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, androstanediol glucuronide, cortisol, testosterone, and SHBG at the first annual visit of the 5-year study period were determined by radioimmunoassays. The only significant difference was found in DHEAS, with cases having higher levels than controls (P < 0.04). DHEAS levels were positively associated with smoking (P < 0.001), alcohol consumption (P < 0.04) and triglyceride levels (P < 0.002) and with systolic (P < 0.04) and diastolic (P < 0.006) blood pressures, and negatively associated with age (P < 0.01) and HDL-cholesterol (P < 0.03). The association between DHEAS and the CHD risk was studied using logistic regression analyses with the classical risk factors--age, smoking, blood pressure, and lipid levels--as covariates in the models. Studies of the joint effects of age and DHEAS disclosed that the risk associated with elevated DHEAS was confirmed to older men (odds ratio (OR) 7.3, 95%, CI 2.3-23.3). A similar analysis with smoking revealed that the DHEAS-related risk was mainly found in smokers (OR 3.4, 95% CI 1.5-8.2). One possible explanation for these results is that some form of mild steroid biosynthetic defect of the adrenals or functional adrenal hyperplasia associated with high DHEAS levels increases the CHD risk in this population.
我们采用巢式病例对照设计,研究了肾上腺雄激素、皮质醇、睾酮和性激素结合球蛋白(SHBG)作为冠心病危险因素的作用。在赫尔辛基心脏研究的最后4年中,研究人群包括62例发生心脏终点事件的病例和97例服用安慰剂的对照。通过放射免疫分析法测定了5年研究期首次年度访视时血清脱氢表雄酮、硫酸脱氢表雄酮(DHEAS)、雄烯二酮、雄烷二醇葡萄糖醛酸苷、皮质醇、睾酮和SHBG的浓度。仅在DHEAS方面发现了显著差异,病例组水平高于对照组(P < 0.04)。DHEAS水平与吸烟(P < 0.001)、饮酒(P < 0.04)和甘油三酯水平(P < 0.002)呈正相关,与收缩压(P < 0.04)和舒张压(P < 0.006)呈正相关,与年龄(P < 0.01)和高密度脂蛋白胆固醇(P < 0.03)呈负相关。使用逻辑回归分析,以年龄、吸烟、血压和血脂水平等经典危险因素作为模型中的协变量,研究了DHEAS与冠心病风险之间的关联。年龄和DHEAS联合效应的研究表明,DHEAS升高相关的风险在老年男性中得到证实(比值比(OR)7.3,95%可信区间2.3 - 23.3)。对吸烟进行的类似分析表明,DHEAS相关风险主要见于吸烟者(OR 3.4,95%可信区间1.5 - 8.2)。这些结果的一种可能解释是,肾上腺某种形式的轻度类固醇生物合成缺陷或与高DHEAS水平相关的功能性肾上腺增生增加了该人群的冠心病风险。