Table 1_Associations of polyunsaturated fatty acids and genetic predisposition with cardiovascular risk among hypertensive adults.docx

BackgroundHypertension is linked to elevated cardiovascular morbidity and mortality. Research findings regarding cardiovascular benefits of polyunsaturated fatty acids (PUFAs) are inconsistent, possibly due to unbalanced N6FA/N3FA (omega-6 to omega-3 polyunsaturated fatty) ratios and genetic predispositions in PUFAs utilization and cardiovascular disease (CVD) risk. This study investigates the association between plasma PUFAs and CVD risk among hypertensive adults, stratified by the polygenic risk score (PRS) for PUFAs and CVD.
MethodsThe study analyzed 135,969 hypertensive adults from the UK Biobank. Cox regression models were employed to assess the links between PUFAs and cardiovascular outcomes, as well as the moderating effect of PRS.
ResultsDuring the follow-up, 22,084 (16.2%) of participants experienced CVD events, and 2,336 (1.7%) and 13,823 (10.2%) died from CVD and all causes, respectively. Higher blood levels of total polyunsaturated fatty acids (Total PUFA), N3FA, N6FA, docosahexaenoic acid (DHA), and linoleic acid (LA) were associated with lower CVD incidence and mortality, for instance, the hazard ratio for N3FA was 0.745 [95% confidence interval (0.698, 0.796)]. Furthermore, the N6FA/N3FA ratio showed a positive association with CVD incidence and mortality, with the point of minimum risk estimated at approximately 8.70 based on restricted cubic spline analysis. Protective associations of Total PUFA, N6FA, and LA with CVD incidence were stronger in individuals with lower CVD – PRS scores.
ConclusionDespite the general cardiovascular benefits of PUFAs, a higher N6FA/N3FA ratio was associated with an elevated risk of CVD in hypertensive participants. The benefits of PUFAs are greater in those with lower genetic CVD risk. This emphasizes the need to consider N6FA/N3FA balance and genetic predisposition when assessing health impact of PUFAs on CVD.

背景：高血压与升高的心血管发病率和死亡率显著相关。目前关于多不饱和脂肪酸（polyunsaturated fatty acids, PUFAs）的心血管获益的研究结论尚存争议，这可能与omega-6多不饱和脂肪酸与omega-3多不饱和脂肪酸的比值失衡，以及多不饱和脂肪酸利用和心血管疾病（cardiovascular disease, CVD）风险相关的遗传易感性有关。本研究探讨高血压成人血浆多不饱和脂肪酸水平与心血管疾病风险的关联，并按多不饱和脂肪酸和心血管疾病的多基因风险评分（polygenic risk score, PRS）进行分层分析。
方法：本研究对英国生物银行（UK Biobank）中的135969名高血压成人进行了分析，采用Cox回归模型评估多不饱和脂肪酸与心血管结局的关联，以及多基因风险评分的调节作用。
结果：随访期间，共计22084名（16.2%）参与者发生心血管疾病事件，2336名（1.7%）和13823名（10.2%）参与者分别死于心血管疾病和全因死亡。血浆总多不饱和脂肪酸（Total PUFA）、omega-3多不饱和脂肪酸（N3FA）、omega-6多不饱和脂肪酸（N6FA）、二十二碳六烯酸（docosahexaenoic acid, DHA）以及亚油酸（linoleic acid, LA）水平越高，心血管疾病的发病率和死亡率越低。例如，omega-3多不饱和脂肪酸的风险比为0.745[95%置信区间（0.698, 0.796）]。此外，omega-6/omega-3比值与心血管疾病发病率和死亡率呈正相关，基于限制性立方样条分析估算的最低风险点约为8.70。总多不饱和脂肪酸、omega-6多不饱和脂肪酸以及亚油酸对心血管疾病发病率的保护作用，在心血管疾病多基因风险评分较低的个体中更为显著。
结论：尽管多不饱和脂肪酸总体上具有心血管获益，但较高的omega-6/omega-3比值与高血压参与者的心血管疾病风险升高相关。多不饱和脂肪酸的获益在心血管疾病遗传风险较低的人群中更为明显。这一结果强调，在评估多不饱和脂肪酸对心血管疾病的健康影响时，需要考虑omega-6/omega-3的平衡以及遗传易感性。