Background This study compared the strength and causality of associations between major risk factors for cardiovascular disease (CVD) and the four major CVDs: myocardial infarction, ischaemic stroke, heart failure and atrial fibrillation. Both a long-term follow-up in an observational cohort and Mendelian randomisation (MR) were used for this aim. Methods In the Uppsala Longitudinal Study of Adult Men study, 2322 men, all aged 50 years, were assessed for CVD risk factors and then followed for four decades regarding incident CVDs. The two-sample MR part used public available Genome-Wide Association Study (GWAS) data. Results In multivariate analyses, systolic blood pressure was overall by far the most important risk factor, since it was related to all four CVDs, both in observational and MR analyses. Body mass index was the second most overall important risk factor, being linked to all four CVDs, except ischaemic stroke, both in observational and MR analyses. Smoking was an important risk factor for ischaemic stroke and heart failure, both in observational and MR analyses, while low-density lipoprotein-cholesterol mainly was related to myocardial infarction. Diabetes was mainly a causal risk factor for incident myocardial infarction and heart failure. Neither HDL-cholesterol nor triglycerides were of major importance as risk factors in these multivariable models. Conclusion By combining long-term observational data with genetic data, we show that the impact and causal role of specific established cardiovascular risk factors varies between different major CVDs. Systolic blood pressure was causally related to all four cardiovascular outcomes and was therefore, overall, the most important risk factor. Data are available on reasonable request. Due to Swedish law and the Ethical Committee permission, health data at the individual level cannot be made available online as an open source for the public. Data are however available by a request sent to the corresponding author. Due to Swedish law and the Ethical Committee permission, health data at the individual level cannot be made available online as an open source for the public. Data are however available by a request sent to the corresponding author.

中文翻译：

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主要心血管疾病危险因素的影响：终生观察和孟德尔随机化结果的比较

背景 本研究比较了心血管疾病 (CVD) 主要危险因素与四种主要 CVD：心肌梗塞、缺血性中风、心力衰竭和心房颤动之间关联的强度和因果关系。为此目的使用了观察性队列的长期随访和孟德尔随机化 (MR)。方法在成年男性研究的乌普萨拉纵向研究中，对 2322 名年龄均 50 岁的男性进行了 CVD 风险因素评估，然后对 CVD 事件进行了 40 年的随访。两样本 MR 部分使用了公开可用的全基因组关联研究 (GWAS) 数据。结果在多变量分析中，收缩压总体上是最重要的危险因素，因为它与所有四种 CVD 相关，无论是在观察性分析还是 MR 分析中。在观察性和 MR 分析中，体重指数是第二大总体重要风险因素，与除缺血性中风之外的所有四种 CVD 相关。在观察性和 MR 分析中，吸烟是缺血性中风和心力衰竭的重要危险因素，而低密度脂蛋白胆固醇主要与心肌梗塞有关。糖尿病主要是发生心肌梗塞和心力衰竭的危险因素。在这些多变量模型中，HDL-胆固醇和甘油三酯都不是最重要的危险因素。结论通过将长期观察数据与遗传数据相结合，我们表明特定既定心血管危险因素的影响和因果作用在不同的主要 CVD 之间存在差异。收缩压与所有四种心血管结局均存在因果关系，因此总体而言，它是最重要的风险因素。可应合理要求提供数据。由于瑞典法律和伦理委员会的许可，个人层面的健康数据不能作为开放源在线提供给公众。然而，数据可通过发送给相应作者的请求获得。由于瑞典法律和伦理委员会的许可，个人层面的健康数据不能作为开放源在线提供给公众。然而，数据可通过发送给相应作者的请求获得。个人层面的健康数据不能作为公开来源在线提供给公众。然而，数据可通过发送给相应作者的请求获得。由于瑞典法律和伦理委员会的许可，个人层面的健康数据不能作为开放源在线提供给公众。然而，数据可通过发送给相应作者的请求获得。个人层面的健康数据不能作为公开来源在线提供给公众。然而，数据可通过发送给相应作者的请求获得。由于瑞典法律和伦理委员会的许可，个人层面的健康数据不能作为开放源在线提供给公众。然而，数据可通过发送给相应作者的请求获得。