吸烟对血压和静息心率的影响：CARTA 联盟的孟德尔随机化荟萃分析
Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium.
作者信息
Linneberg Allan, Jacobsen Rikke K, Skaaby Tea, Taylor Amy E, Fluharty Meg E, Jeppesen Jørgen L, Bjorngaard Johan H, Åsvold Bjørn O, Gabrielsen Maiken E, Campbell Archie, Marioni Riccardo E, Kumari Meena, Marques-Vidal Pedro, Kaakinen Marika, Cavadino Alana, Postmus Iris, Ahluwalia Tarunveer S, Wannamethee S Goya, Lahti Jari, Räikkönen Katri, Palotie Aarno, Wong Andrew, Dalgård Christine, Ford Ian, Ben-Shlomo Yoav, Christiansen Lene, Kyvik Kirsten O, Kuh Diana, Eriksson Johan G, Whincup Peter H, Mbarek Hamdi, de Geus Eco J C, Vink Jacqueline M, Boomsma Dorret I, Smith George Davey, Lawlor Debbie A, Kisialiou Aliaksei, McConnachie Alex, Padmanabhan Sandosh, Jukema J Wouter, Power Chris, Hyppönen Elina, Preisig Martin, Waeber Gerard, Vollenweider Peter, Korhonen Tellervo, Laatikainen Tiina, Salomaa Veikko, Kaprio Jaakko, Kivimaki Mika, Smith Blair H, Hayward Caroline, Sørensen Thorkild I A, Thuesen Betina H, Sattar Naveed, Morris Richard W, Romundstad Pål R, Munafò Marcus R, Jarvelin Marjo-Riitta, Husemoen Lise Lotte N
出版信息
Circ Cardiovasc Genet. 2015 Dec;8(6):832-41. doi: 10.1161/CIRCGENETICS.115.001225. Epub 2015 Nov 4.
BACKGROUND
Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood.
METHODS AND RESULTS
Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day.
CONCLUSIONS
This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.
背景
吸烟是心血管疾病的重要危险因素，但吸烟与血压之间的关联机制尚不清楚。
方法与结果
来自23项基于人群研究的141317名参与者（62666名从不吸烟者、40669名曾经吸烟者、37982名当前吸烟者）的数据被纳入吸烟状况和吸烟量与收缩压、舒张压、高血压及静息心率之间关联的观察性和孟德尔随机化荟萃分析。对于孟德尔随机化分析，基因变异rs16969968/rs1051730被用作当前吸烟者吸烟量的替代指标。在观察性分析中，与从不吸烟相比，当前吸烟与较低的收缩压和舒张压以及较低的高血压风险相关，但与较高的静息心率相关。在当前吸烟者的观察性分析中，每天吸烟量每增加1支，静息心率较高（0.21次/分钟；95%置信区间0.19；0.24），舒张压略高（0.05毫米汞柱；95%置信区间0.02；0.08），收缩压略高（0.08毫米汞柱；95%置信区间0.03；0.13）。然而在当前吸烟者的孟德尔随机化分析中，尽管rs16969968/rs1051730的每个吸烟增加等位基因与较高的静息心率相关（0.36次/分钟/等位基因；95%置信区间0.18；0.54），但与舒张压、收缩压或高血压没有强关联。这表明每天吸20支烟的人心率会高7次/分钟。
结论
这项孟德尔随机化荟萃分析支持吸烟量与较高静息心率之间存在因果关联，但与血压无关。这些发现表明，吸烟的部分心血管风险可能通过增加静息心率起作用。
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