Genetically Predicted Differences in Systolic Blood Pressure and Risk of Cardiovascular and Noncardiovascular Diseases: A Mendelian Randomization Study in Chinese Adults.
Genetically Predicted Differences in Systolic Blood Pressure and Risk of Cardiovascular and Noncardiovascular Diseases: A Mendelian Randomization Study in Chinese Adults.
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DOI：
10.1161/hypertensionaha.122.20120
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
China Kadoorie Biobank Collaborative Group‡
中科院分区：
文献类型：
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作者：
Clarke R;Wright N;Walters R;Gan W;Guo Y;Millwood IY;Yang L;Chen Y;Lewington S;Lv J;Yu C;Avery D;Lin K;Wang K;Peto R;Collins R;Li L;Bennett DA;Parish S;Chen Z;China Kadoorie Biobank Collaborative Group‡
孟德尔的收缩压(SBP)随机研究可以评估遗传预测的SBP差异与主要疾病结局之间的联系的形式和强度，并且在观察性分析中较少受到偏差的限制。本研究旨在比较正常SBP和遗传预测的SBP与重大心血管疾病(CVD)结局的关系，总体上以及SBP水平、年龄和性别。中国嘉道理生物库对489,495名40-79岁的成年人和86,060名有遗传数据的成年人进行了为期12年的前瞻性研究。结果包括主要血管事件(MVE；观察性/遗传学分析中的59,490/23,151)及其组成部分(缺血性中风[IS；n=39,513/12,043]，脑内出血[ICH；7,336/5,243]，重大冠状动脉事件[MCE；7,871/4,187])。基因预测的SBP使用了从欧洲血统全基因组研究中获得的460个变种。Cox回归估计发生心血管事件的调整危险比(HR)降至通常的SBP水平120毫米汞柱。观察性和遗传性分析均显示SBP与MVE和其他主要心血管疾病类型呈对数线性正相关，范围在120-170毫米汞柱。与观察分析一致的是，遗传预测的SBP每高10 mm HgHR，ICH(1.71，95%CI 1.58-1.87)比IS(1.37，1.30-1.45)或MCE(1.29，1.18-1.42)高2倍。遗传分析还显示，年轻人MVE的HR值(1.69，95%可信区间1.54-1.86)是老年人(1.28，1.18-1.38)的2倍。这些发现支持在更年轻的年龄和低于高血压的传统界限开始降压治疗，以最大限度地预防心血管疾病，尽管老年人患心血管疾病的绝对风险要大得多。
Mendelian randomization studies of systolic blood pressure (SBP) can assess the shape and strength of the associations of genetically-predicted differences in SBP with major disease outcomes and are less constrained by biases in observational analyses. This study aimed to compare the associations of usual and genetically-predicted SBP with major cardiovascular disease (CVD) outcomes, overall and by levels of SBP, age and sex. The China Kadoorie Biobank involved a 12-year follow-up of a prospective study of 489,495 adults aged 40-79 years with no prior CVD and 86,060 with genetic data. Outcomes included major vascular events (MVE; 59,490/23,151 in observational/genetic analyses), and its components (ischemic stroke [IS; n=39,513/12,043], intra-cerebral hemorrhage [ICH; 7,336/5,243], major coronary events [MCE; 7,871/4,187]). Genetically-predicted SBP used 460 variants obtained from European ancestry genome-wide studies. Cox regression estimated adjusted hazard ratios (HRs) for incident CVD outcomes down to usual SBP levels of 120 mmHg. Both observational and genetic analyses demonstrated log-linear positive associations of SBP with MVE and other major CVD types in the range 120-170 mmHg. Consistent with the observational analyses, the HRs per 10 mmHg higher genetically-predicted SBP were 2-fold greater for ICH (1.71, 95% CI 1.58-1.87) than for IS (1.37, 1.30-1.45) or MCE (1.29, 1.18-1.42). Genetic analyses also demonstrated 2-fold greater HRs for MVE in younger (1.69, 95% CI 1.54-1.86) than in older people (1.28, 1.18-1.38). The findings provide support for initiation of blood pressure-lowering treatment at younger ages and below the conventional cut-offs for hypertension to maximize CVD prevention, albeit the absolute risks of CVD are far greater in older people.