Nuffield Department of Population Health, University of Oxford Big Data Institute, Old Road Campus, Headington, Oxford, OX3 7LF, UK.
Botswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Plot No. 1836, Northring Road, Gaborone, Botswana.
Eur J Prev Cardiol. 2022 May 6;29(6):925-937. doi: 10.1093/eurjpc/zwab192.
Many studies have investigated associations between polygenic risk scores (PRS) and the incidence of cardiovascular disease (CVD); few have examined whether risk factor-related PRS predict CVD outcomes among adults treated with risk-modifying therapies. We assessed whether PRS for systolic blood pressure (PRSSBP) and for low-density lipoprotein cholesterol (PRSLDL-C) were associated with achieving SBP and LDL-C-related targets, and with major adverse cardiovascular events (MACE: non-fatal stroke or myocardial infarction, CVD death, and revascularization procedures).
Using observational data from the UK Biobank (UKB), we calculated PRSSBP and PRSLDL-C and constructed two sub-cohorts of unrelated adults of White British ancestry aged 40-69 years and with no history of CVD, who reported taking medications used in the treatment of hypertension or hypercholesterolaemia. Treatment effectiveness in achieving adequate risk factor control was ascertained using on-treatment blood pressure (BP) or LDL-C levels measured at enrolment (uncontrolled hypertension: BP ≥ 140/90 mmHg; uncontrolled hypercholesterolaemia: LDL-C ≥ 3 mmol/L). We conducted multivariable logistic and Cox regression modelling for incident events, adjusting for socioeconomic characteristics, and CVD risk factors. There were 55 439 participants using BP lowering therapies (51.0% male, mean age 61.0 years, median follow-up 11.5 years) and 33 787 using LDL-C lowering therapies (58.5% male, mean age 61.7 years, median follow-up 11.4 years). PRSSBP was associated with uncontrolled hypertension (odds ratio 1.70; 95% confidence interval: 1.60-1.80) top vs. bottom quintile, equivalent to a 5.4 mmHg difference in SBP, and with MACE [hazard ratio (HR) 1.13; 1.04-1.23]. PRSLDL-C was associated with uncontrolled hypercholesterolaemia (HR 2.78; 2.58-3.00) but was not associated with subsequent MACE.
We extend previous findings in the UKB cohort to examine PRSSBP and PRSLDL-C with treatment effectiveness. Our results indicate that both PRSSBP and PRSLDL-C can help identify individuals who, despite being on treatment, have inadequately controlled SBP and LDL-C, and for SBP are at higher risk for CVD events. This extends the potential role of PRS in clinical practice from identifying patients who may need these interventions to identifying patients who may need more intensive intervention.
许多研究调查了多基因风险评分（PRS）与心血管疾病（CVD）发病率之间的关联；很少有研究调查与危险因素相关的PRS 是否可预测接受风险修正治疗的成年人的 CVD 结局。我们评估了收缩压相关 PRS（PRSBP）和低密度脂蛋白胆固醇相关 PRS（PRSLDL-C）是否与达到收缩压和 LDL-C 相关目标以及主要不良心血管事件（MACE：非致死性中风或心肌梗死、CVD 死亡和血运重建手术）相关。
使用英国生物库（UKB）的观察性数据，我们计算了 PRSSBP 和 PRSLDL-C，并构建了两个亚队列，包括无 CVD 病史、报告服用降压或降脂药物的 40-69 岁白种英国血统的无关成年人。通过在入组时测量的治疗中血压（BP）或 LDL-C 水平来确定治疗效果，以达到充分的危险因素控制（未控制的高血压：BP≥140/90mmHg；未控制的高胆固醇血症：LDL-C≥3mmol/L）。我们使用多变量逻辑回归和 Cox 回归模型进行了事件分析，调整了社会经济特征和 CVD 危险因素。共有 55439 名参与者使用降压治疗（51.0%为男性，平均年龄 61.0 岁，中位随访时间 11.5 年），33787 名参与者使用降脂治疗（58.5%为男性，平均年龄 61.7 岁，中位随访时间 11.4 年）。PRSBP 与未控制的高血压相关（优势比 1.70；95%置信区间：1.60-1.80），最高五分位与最低五分位相比，相当于收缩压差异 5.4mmHg，与 MACE 相关[风险比（HR）1.13；1.04-1.23]。PRSLDL-C 与未控制的高胆固醇血症相关（HR 2.78；2.58-3.00），但与随后的 MACE 无关。
我们在 UKB 队列中扩展了先前的研究结果，以检查 PRSSBP 和 PRSLDL-C 与治疗效果的关系。我们的结果表明，PRSBP 和 PRSLDL-C 均可帮助识别尽管接受治疗，但收缩压和 LDL-C 控制不佳的个体，且收缩压较高的个体发生 CVD 事件的风险更高。这扩展了 PRS 在临床实践中的潜在作用，从识别可能需要这些干预措施的患者扩展到识别可能需要更强化干预措施的患者。
