Risk Factors for Incidence of Cardiovascular Diseases and All-Cause Mortality in a Middle Eastern Population over a Decade Follow-up: Tehran Lipid and Glucose Study

Background
To examine the association between potentially modifiable risk factors with cardiovascular disease (CVD) and all-cause mortality and to quantify their population attributable fractions (PAFs) among a sample of Tehran residents.
Methods
Overall, 8108 participants (3686 men) aged≥30 years, were investigated. To examine the association between risk factors and outcomes, multivariate sex-adjusted Cox proportional hazard regression analysis were conducted, using age as time-scale in two models including general/central adiposity: 1)adjusted for different independent variables including smoking, education, family history of CVD and sex for both outcomes and additionally adjusted for prevalent CVD for all-cause mortality 2)further adjusted for obesity mediators (hypertension, diabetes, lipid profile and chronic kidney disease). Separate models were used including either general or central adiposity.
Results
During median follow-up of >10 years, 827 first CVD events and 551 deaths occurred. Both being overweight (hazard ratio (HR), 95%CI: 1.41, 1.18–1.66, PAF 13.66) and obese (1.51, 1.24–1.84, PAF 9.79) played significant roles for incident CVD in the absence of obesity mediators. Predicting CVD, in the presence of general adiposity and its mediators, significant positive associations were found for hypercholesterolemia (1.59, 1.36–1.85, PAF 16.69), low HDL-C (1.21, 1.03–1.41, PAF 12.32), diabetes (1.86, 1.57–2.27, PAF 13.87), hypertension (1.79, 1.46–2.19, PAF 21.62) and current smoking (1.61, 1.34–1.94, PAF 7.57). Central adiposity remained a significant positive predictor, even after controlling for mediators (1.17, 1.01–1.35, PAF 7.55). For all-cause mortality, general/central obesity did not have any risk even in the absence of obesity mediators. Predictors including diabetes (2.56, 2.08–3.16, PAF 24.37), hypertension (1.43, 1.11–1.84, PAF 17.13), current smoking (1.75, 1.38–2.22, PAF 7.71), and low education level (1.59, 1.01–2.51, PAF 27.08) were associated with higher risk, however, hypertriglyceridemia (0.83, 0.68–1.01) and being overweight (0.71, 0.58–0.87) were associated with lower risk.
Conclusions
Modifiable risk factors account for more than 70% risk for both CVD and mortality events.

研究背景：旨在探讨潜在可干预危险因素与心血管疾病（cardiovascular disease, CVD）及全因死亡率（all-cause mortality）的关联，并量化德黑兰居民队列中这些因素的人群归因分数（population attributable fractions, PAFs）。
研究方法：本研究共纳入8108名年龄≥30岁的参与者（其中男性3686名）。为探讨危险因素与研究结局的关联，本研究采用以年龄为时间尺度的多因素性别校正Cox比例风险回归模型，针对全身性肥胖/中心性肥胖分别构建两类分析模型：1）模型1：针对两类结局均校正吸烟、受教育水平、心血管疾病家族史及性别因素；针对全因死亡率，还额外校正基线心血管疾病病史。2）模型2：在模型1的基础上，进一步校正肥胖相关中介变量（高血压、糖尿病、血脂谱及慢性肾脏病（chronic kidney disease））。两类模型均分别针对全身性肥胖与中心性肥胖单独构建。
研究结果：中位随访时长超过10年期间，共发生827例首次心血管疾病事件与551例全因死亡病例。在未校正肥胖中介变量时，超重（风险比（hazard ratio, HR），95%置信区间（confidence interval, CI）：1.41, 1.18–1.66，人群归因分数13.66%）与肥胖（1.51, 1.24–1.84，9.79%）均与心血管疾病发病风险升高显著相关。在校正全身性肥胖及其中介变量后，高胆固醇血症（hypercholesterolemia）（1.59, 1.36–1.85，16.69%）、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol, HDL-C）降低（1.21, 1.03–1.41，12.32%）、糖尿病（1.86, 1.57–2.27，13.87%）、高血压（1.79, 1.46–2.19，21.62%）以及当前吸烟（1.61, 1.34–1.94，7.57%）均与心血管疾病发病风险升高存在显著正相关。即使校正中介变量后，中心性肥胖仍为心血管疾病发病的显著正向预测因素（1.17, 1.01–1.35，7.55%）。针对全因死亡率而言，无论是否校正肥胖中介变量，全身性/中心性肥胖均未显示出显著死亡风险。糖尿病（2.56, 2.08–3.16，24.37%）、高血压（1.43, 1.11–1.84，17.13%）、当前吸烟（1.75, 1.38–2.22，7.71%）以及低受教育水平（1.59, 1.01–2.51，27.08%）均与全因死亡风险升高相关；而高甘油三酯血症（hypertriglyceridemia）（0.83, 0.68–1.01）与超重（0.71, 0.58–0.87）则与死亡风险降低相关。
研究结论：可干预危险因素可解释心血管疾病与全因死亡事件超过70%的发病/死亡风险。