Foody J M, Milberg J A, Robinson K, Pearce G L, Jacobsen D W, Sprecher D L
Department of Cardiology, Section of Preventive Cardiology and Rehabilitation, The Cleveland Clinic Foundation, OH 44195, USA.
Arterioscler Thromb Vasc Biol. 2000 Feb;20(2):493-9. doi: 10.1161/01.atv.20.2.493.
A biochemical link between homocysteine (tHcy) and lipoprotein(a) [Lp(a)] related to fibrin binding has been proposed. This hypothesis has not been specifically examined in human subjects. We sought to determine in a clinical setting whether these risk factors would interact to increase coronary artery disease (CAD) risk. We performed a cross-sectional analysis of 750 men and 403 women referred to a preventive cardiology clinic at the Cleveland Clinic Foundation, in whom baseline tHcy and Lp(a) data were available. Logistic regression after adjusting for standard cardiovascular risk factors was used to estimate the relative risk of CAD in patients with an Lp(a) >/=30 mg/dL and a tHcy >/=17 micromol/L. Neither isolated high tHcy (odds ratio [OR]=1.06, P=0.89) nor isolated high Lp(a) (OR=1.15, P=0.60) appeared to be associated with CAD in women. However, strong evidence of an association was seen when both risk factors were present (OR=4.83, P=0.003). Moreover, this increased risk showed evidence of an interactive effect beyond that attributable to either additive or multiplicative effects of tHcy and Lp(a) (P=0.03). In contrast, both elevated tHcy (OR=1.93, P=0. 05) and elevated Lp(a) (OR=1.87, P=0.01) showed evidence of being independent risk factors for CAD in men. The presence of both risk factors in men did not appear to confer additional risk (OR=2.00, P=0.09), even though ORs as high as 12.4 were observed within specific age intervals. Consistent with prior studies, tHcy and Lp(a) are risk factors, either independently or in concert, for CAD in this clinical population. More significantly, we found evidence that when both risk factors were present in women, the associated risk was greater than what would be expected if the 2 risks were simply acting independently. The absence of such an interactive effect in men may be due to the confounding effects of age manifested as "survivor bias." These clinical findings provide insights into the potential roles of both tHcy and Lp(a) in the pathogenesis of atherosclerosis.
同型半胱氨酸（总同型半胱氨酸）与脂蛋白(a) [Lp(a)] 之间存在与纤维蛋白结合相关的生化联系这一假说已被提出。但这一假说尚未在人类受试者中得到具体验证。我们试图在临床环境中确定这些风险因素是否会相互作用以增加冠状动脉疾病（CAD）风险。我们对克利夫兰诊所基金会预防心脏病科转诊的750名男性和403名女性进行了横断面分析，这些人有基线总同型半胱氨酸和Lp(a)数据。在对标准心血管风险因素进行调整后，采用逻辑回归来估计Lp(a)≥30mg/dL且总同型半胱氨酸≥17μmol/L的患者患CAD的相对风险。在女性中，单独的高总同型半胱氨酸（优势比[OR]=1.06，P=0.89）或单独的高Lp(a)（OR=1.15，P=0.60）似乎都与CAD无关。然而，当两种风险因素都存在时，有强有力的证据表明存在关联（OR=4.83，P=0.003）。此外，这种增加的风险显示出一种交互作用，其作用超过了总同型半胱氨酸和Lp(a)的相加或相乘作用（P=0.03）。相比之下，在男性中，升高的总同型半胱氨酸（OR=1.93，P=0.05）和升高的Lp(a)（OR=1.87，P=0.01）都显示出是CAD独立风险因素的证据。在男性中，两种风险因素都存在似乎并未带来额外风险（OR=2.00，P=0.09），尽管在特定年龄区间观察到高达12.4的OR值。与先前研究一致，在这一临床人群中，总同型半胱氨酸和Lp(a)单独或共同都是CAD的风险因素。更重要的是，我们发现有证据表明，当女性同时存在这两种风险因素时，相关风险大于如果这两种风险只是简单地独立起作用时所预期的风险。男性中不存在这种交互作用可能是由于年龄的混杂效应表现为“幸存者偏差”。这些临床发现为总同型半胱氨酸和Lp(a)在动脉粥样硬化发病机制中的潜在作用提供了见解。
