降低低密度脂蛋白

降低低密度脂蛋白，越早越好——一项长期随机对照试验评估早期降低低密度脂蛋白价值

芝加哥（2012年3月26日）——由于积聚的脂肪和胆固醇引起的冠状动脉粥样硬化，可以导致心脏病发作和其他形式的冠心病（CHD）。降低低密度脂蛋白（LDL）或“坏”胆固醇，降低了冠心病风险，研究人员发现，早期降低LDL与晚期他汀治疗相比，可降低3倍多的冠心病风险。该研究已发表在第61届美国心脏病学会年会上。

冠心病已悄然发展了十余年，大多数人从那个时候开始已进行降低LDL治疗。因为冠状动脉粥样硬化往往自早期开始，早年开始降低LDL能更大程度的降低冠心病风险。研究人员试图通过使用基因数据进行了一系列“自然”随机对照试验检验这一假设，涉及一百万余研究参与者。

Brian A. Ference博士作为试验的主要研究者，也是韦恩州立大学医学院心血管基因组研究中心主任说“我们的研究表明，有利于降低LDL取决于时间和LDL降低的程度。早期降低LDL所得到的获益也在于降低的幅度。这意味着，早期控制饮食和锻炼可能与他汀类药物及其他药物在减少冠心病的危险方面同样有效。”

在动脉粥样硬化发展开始之前，就早期降低LDL，理所当然会更有效地减少心脏病发作，但证明这一假说有一定困难。传统的随机试验必须遵循一个非常大数目的年轻无症状人群通过几十年来测试这一假说。作为替代，研究人员使用了一种新的研究设计称为孟德尔随机对照试验（mRCT），研究DNA序列的九个单核苷酸多态性（SNPs）或单序列变化对降低LDL 水平的影响。因为每个单核苷酸多态性是随机分配的，由开始即决定是否降低LDL。研究人员发现，所有九个单核苷酸多态性较为一致的每降低1 mmol/L (38.67 mg/dl)LDL就减少了50 - 60％的冠心病风险。每降低2 mmol/L (77.34 mg/dl)LDL可以降低80％的冠心病风险。

Ference博士说道：“我们的研究结果表明，降低LDL得到的临床获益需要通过早期开始行动。”冠心病是目前世界上最常见的死亡和残疾原因。治疗冠心病及其危险因素是一笔昂贵的大比例医疗保健支出。Ference博士认为，这项研究的结果表明，着眼于早期开始的，并且长期、持续的LDL降低，有可能大大减少全球的冠心病负担。

英文原文：

CHICAGO (March 26, 2012) — Coronary atherosclerosis – a hardening of the arteries due to a build-up of fat and cholesterol – can lead to heart attacks and other forms of coronary heart disease (CHD). Lowering low-density lipoprote in (LDL), or “bad” cholesterol, reduces the risk of CHD, and researchers foun d that lowering LDL beginning early in life resulted in a three-fold greater re duction in the risk of CHD than treatment with a statin started later in life, according to research presented today at the American College of Cardiology’s 61st Annual Scientific Session. The Scientific Session, the premier cardiovascu lar medical meeting, brings cardiovascular professionals together to further ad vances in the field.

By the time most people begin treatment to lower LDL, CHD has often been qu ietly developing for decades. Because coronary atherosclerosis begins early in life, lowering LDL at a younger age may produce even greater reductions in the risk of CHD. Researchers sought to test this hypothesis by using genetic data t o conduct a series of “natural” randomized controlled trials involving over o ne million study participants.

“Our study shows that the benefit of lowering LDL cholesterol depends on b oth the timing and the magnitude of LDL reduction,” said Brian A. Ference, MD, MPhil, MSc, FACC, director of the cardiovascular genomic research center at Way ne State University School of Medicine and the study’s principal investigator. “The increased benefit of lowering LDL beginning early in life appeared to be independent of how LDL was lowered. This means that diet and exercise are proba bly as effective as statins or other medications at reducing the risk of CHD wh en started early in life.”

Lowering LDL cholesterol at an early age, before the development of atheros clerosis, would understandably be more effective at reducing heart attacks, but testing this hypothesis has proven difficult. A conventional randomized trial would have to follow a very large number of young, asymptomatic people for seve ral decades to test this hypothesis. As an alternative, researchers used a nove l study design called a Mendelian randomized controlled trial (mRCT) to study t he effect of nine single-nucleotide polymorphisms (SNPs), or single-letter chan ges in DNA sequence, each of which is associated with lower levels of LDL chole sterol. Because each of these SNPs is allocated randomly at the time of concept ion, inheriting one of these SNPs is like being randomly allocated to a treatme nt that lowers LDL cholesterol beginning at birth. The researchers found that a ll nine SNPs were associated with a consistent 50-60 percent reduction in the r isk of CHD for each 1 mmol/L (38.67 mg/dl) lower lifetime exposure to LDL chole sterol. Lowering LDL by 2 mmol/L (77.34 mg/dl) could reduce the risk of CHD by almost 80 percent.

“The results of our study demonstrate that the clinical benefit of lowerin g LDL can be substantially improved by initiating therapies to lower LDL choles terol beginning early in life,” Dr. Ference said.

Coronary heart disease is the most common cause of death and disability through out the world. Treatment of CHD and its risk factors is costly and consumes a large proportion of health care expenditures. Dr. Ference believes that the res ults of this study suggest that focusing on prolonged and sustained reductions in LDL cholesterol beginning early in life has the potential to substantially r educe the global burden of CHD.