The joint effects of apolipoprotein B, apolipoprotein A1, LDL cholesterol, and HDL cholesterol on risk: 3510 cases of acute myocardial infarction and 9805 controls.
The joint effects of apolipoprotein B, apolipoprotein A1, LDL cholesterol, and HDL cholesterol on risk: 3510 cases of acute myocardial infarction and 9805 controls.
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DOI：
10.1093/eurheartj/ehp221
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发表时间：
2009-09
影响因子：
39.3
通讯作者：
International Studies of Infarct Survival Collaborators
中科院分区：
文献类型：
--
作者：
Parish S;Peto R;Palmer A;Clarke R;Lewington S;Offer A;Whitlock G;Clark S;Youngman L;Sleight P;Collins R;International Studies of Infarct Survival Collaborators
血浆载脂蛋白B（apo B）（LDL颗粒上的主要表面蛋白）和LDL-C（这些颗粒中的胆固醇含量）水平密切相关，单独考虑，是阳性风险因素。血浆载脂蛋白A1（HDL颗粒上的主要表面蛋白）和HDL-C（这些颗粒中的胆固醇含量）的水平也彼此密切相关，单独考虑，是负风险因素。这四个风险因素的相互依赖性尚不清楚。英国医院3510例急性心肌梗死患者（既往无血管疾病、糖尿病或他汀类药物使用）和9805例对照的病例对照研究。相对风险（年龄、性别、吸烟和肥胖校正）与apoB的相关性比与LDL-C的相关性更强，并且，考虑到apoB，与apoA 1的负相关性比与HDL-C的负相关性更强。apoB/apoA 1比值与病例症状发作后的时间无关，在对照组中相隔几年采集的样本中可重复（相关性0.81），并且几乎包含了这四种测量的所有预测能力。其影响是连续的，在整个英国正常范围内是实质性的[相对风险，该比率的顶部与底部十分位数，7.3（95% CI 5.8-9.2）]，并且随年龄变化很小。apoB/apoA 1比值（χ12 = 550）比常用的指标如LDL-C/HDL-C、总/HDL胆固醇、非HDL胆固醇和总胆固醇（χ12分别= 407、334、204和105）更能提供风险信息。考虑到apoB和apoA 1，与LDL-C风险的关系被逆转，并且通过适当考虑两个相关变量的随机测量误差，这种逆转得到了加强。在apoB水平正常的情况下，较低的LDL-C（与较小的LDL颗粒一致）与较高的风险相关（P < 0.0001）。在症状发作后的前8小时内，HDL-C升高约10%，排除了在此类回顾性病例对照研究中对apoA 1和发作前HDL-C与风险的联合关系进行可靠评估。载脂蛋白比率比脂质组分更能提供风险信息。这表明，在特定类型的脂蛋白颗粒（LDL或HDL）中，一些较小和较大的亚型对风险的影响不同。直接测量脂蛋白颗粒的更具体的亚型可能会提供更多关于风险的信息。
Plasma levels of apolipoprotein B (apoB), the main surface protein on LDL particles, and LDL-C, the amount of cholesterol in those particles, are closely correlated and, considered separately, are positive risk factors. Plasma levels of apolipoprotein A1, the main surface protein on HDL particles, and HDL-C, the amount of cholesterol in those particles, are also closely correlated with each other and, considered separately, are negative risk factors. The interdependence of these four risk factors is unclear. Case–control study among 3510 acute myocardial infarction patients (without prior vascular disease, diabetes, or statin use) in UK hospitals and 9805 controls. Relative risks (age, sex, smoking, and obesity-adjusted) were more strongly related to apoB than to LDL-C and, given apoB, more strongly negatively related to apoA1 than to HDL-C. The ratio apoB/apoA1 was uncorrelated with time since symptom onset in cases, was reproducible in samples collected a few years apart in controls (correlation 0.81), and encapsulated almost all the predictive power of these four measurements. Its effect was continuous, substantial throughout the UK normal range [relative risk, top vs. bottom decile of this ratio, 7.3 (95% CI 5.8–9.2)] and varied little with age. The ratio apoB/apoA1 was substantially more informative about risk (χ12 = 550) than were commonly used measures such as LDL-C/HDL-C, total/HDL cholesterol, non-HDL cholesterol, and total cholesterol (χ12 = 407, 334, 204, and 105, respectively). Given apoB and apoA1, the relationship with risk of LDL-C was reversed, and this reversal was strengthened by appropriate allowance for random measurement errors in two correlated variables. Given usual apoB, lower LDL-C (consistent with smaller LDL particles) was associated with higher risk (P < 0.0001). During the first 8 h after symptom onset HDL-C increased by about 10%, precluding reliable assessment of the joint relationship of apoA1 and pre-onset HDL-C with risk in such retrospective case–control studies. Apolipoprotein ratios are more informative about risk than lipid fractions are. This suggests that, among lipoprotein particles of a particular type (LDL or HDL), some smaller and larger subtypes differ in their effects on risk. Direct measurements of even more specific subtypes of lipoprotein particles may be even more informative about risk.
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