Clinical Epidemiology of Renal Disease and Hypertension Unit, Reggio Cal CNR Unit of the Pisa CNR Institute of Clinical Physiology, Pisa, Italy.
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Eur J Clin Invest. 2024 Sep;54(9):e14235. doi: 10.1111/eci.14235. Epub 2024 May 11.
Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies.
The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis.
During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HR: 1.23, 95% CI 1.06-1.43, p =.008) and CV mortality (HR: 1.26, 95% CI 1.03-1.54, p =.03). After multivariate adjustment, these associations were no longer significant (all-cause mortality, HR: 1.16, 95% CI .99-1.36, p =.07; CV mortality, HR: 1.18, 95% CI .95-1.46, p =.14). However, in fully adjusted interaction analyses, a doubling in the risk of this outcome in women was registered (Women, HR: 1.88, 95% CI 1.27-2.78, p =.002; Men, HR: 1.07, 95% CI .83-1.38, p =.61; p for effect modification: .02).
PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.
前蛋白转化酶枯草溶菌素/胰凝乳蛋白酶 9（PCSK9）是一种加速 LDL 受体降解的因子，与普通人群心血管（CV）事件的性别相关风险以及两项针对黑人和韩国血液透析患者的相对较小研究中的全因和 CV 死亡率相关。在这些研究中，性别对作用的修饰作用未经检验。
该研究纳入了 Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria（PROGREDIRE）队列中的 1188 名透析患者。通过比色酶联免疫吸附测定法测量 PCSK9。主要结局是全因和 CV 死亡率。统计分析包括 Cox 回归分析和作用修饰分析。
在中位 2.9 年的随访期间，494 例死亡中，278 例与 CV 相关。在未调整的分析中，PCSK9 水平与全因死亡（HR：1.23，95%CI 1.06-1.43，p=.008）和 CV 死亡率（HR：1.26，95%CI 1.03-1.54，p=.03）相关。经过多变量调整后，这些关联不再显著（全因死亡率，HR：1.16，95%CI.99-1.36，p=.07；CV 死亡率，HR：1.18，95%CI.95-1.46，p=.14）。然而，在完全调整的交互分析中，女性发生这种结局的风险增加了一倍（女性，HR：1.88，95%CI 1.27-2.78，p=.002；男性，HR：1.07，95%CI.83-1.38，p=.61；p 用于修饰作用检验：.02）。
在血液透析患者中，PCSK9 水平与全因死亡率无关，但与一般人群的研究一样，独立于其他危险因素，在该人群中，女性 CV 事件的风险增加了一倍。
