Rana Brinda K, Dhamija Anish, Panizzon Matthew S, Spoon Kelly M, Vasilopoulos Terrie, Franz Carol E, Grant Michael D, Jacobson Kristen C, Kim Kathleen, Lyons Michael J, McCaffery Jeanne M, Stein Phyllis K, Xian Hong, O'Connor Daniel T, Kremen William S
Department of Psychiatry, University of California-San Diego, La Jolla, California, USA.
Am J Hypertens. 2014 Jun;27(6):828-37. doi: 10.1093/ajh/hpt271. Epub 2014 Feb 14.
Elevated blood pressure (BP), a heritable risk factor for many age-related disorders, is commonly investigated in population and genetic studies, but antihypertensive use can confound study results. Routine methods to adjust for antihypertensives may not sufficiently account for newer treatment protocols (i.e., combination or multiple drug therapy) found in contemporary cohorts.
We refined an existing method to impute unmedicated BP in individuals on antihypertensives by incorporating new treatment trends. We assessed BP and antihypertensive use in male twins (n = 1,237) from the Vietnam Era Twin Study of Aging: 36% reported antihypertensive use; 52% of those treated were on multiple drugs.
Estimated heritability was 0.43 (95% confidence interval (CI) = 0.20-0.50) and 0.44 (95% CI = 0.22-0.61) for measured systolic BP (SBP) and diastolic BP (DBP), respectively. We imputed BP for antihypertensives by 3 approaches: (i) addition of a fixed value of 10/5mm Hg to measured SBP/DBP; (ii) incremented addition of mm Hg to BP based on number of medications; and (iii) a refined approach adding mm Hg based on antihypertensive drug class and ethnicity. The imputations did not significantly affect estimated heritability of BP. However, use of our most refined imputation method and other methods resulted in significantly increased phenotypic correlations between BP and body mass index, a trait known to be correlated with BP.
This study highlights the potential usefulness of applying a representative adjustment for medication use, such as by considering drug class, ethnicity, and the combination of drugs when assessing the relationship between BP and risk factors.
血压升高是许多与年龄相关疾病的遗传风险因素，在人群和基因研究中经常被调查，但使用抗高血压药物可能会混淆研究结果。用于调整抗高血压药物的常规方法可能无法充分考虑当代队列中发现的新治疗方案（即联合或多种药物治疗）。
我们通过纳入新的治疗趋势，改进了一种现有的方法来估算正在服用抗高血压药物个体的未用药血压。我们评估了越南时代双生子衰老研究中男性双胞胎（n = 1237）的血压和抗高血压药物使用情况：36%报告使用抗高血压药物；接受治疗的人中52%使用多种药物。
测量的收缩压（SBP）和舒张压（DBP）的估计遗传力分别为0.43（95%置信区间（CI）= 0.20 - 0.50）和0.44（95%CI = 0.22 - 0.61）。我们通过三种方法估算服用抗高血压药物者的血压：（i）在测量的SBP/DBP基础上加上固定值10/5mmHg；（ii）根据药物数量逐步增加血压的mmHg值；（iii）一种改进的方法，根据抗高血压药物类别和种族增加mmHg值。这些估算并未显著影响血压的估计遗传力。然而，使用我们最精细的估算方法和其他方法导致血压与体重指数之间的表型相关性显著增加，体重指数是一种已知与血压相关的性状。
本研究强调了在评估血压与风险因素之间的关系时，应用具有代表性的药物使用调整方法的潜在有用性，例如考虑药物类别、种族和药物组合。
