Association Between High-Density Lipoprotein Cholesterol Levels and Adverse Cardiovascular Outcomes in High-risk Populations
Association Between High-Density Lipoprotein Cholesterol Levels and Adverse Cardiovascular Outcomes in High-risk Populations
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DOI：
10.1001/jamacardio.2022.0912
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发表时间：
2022-05-18
期刊：
影响因子：
24
通讯作者：
Quyyumi, Arshed A.
中科院分区：
文献类型：
--
作者：
Liu, Chang;Dhindsa, Devinder;Quyyumi, Arshed A.
重要性 先前的研究表明，高密度脂蛋白胆固醇 (HDL-C) 水平越高，心血管风险就越低。然而，最近在一般人群中的数据显示，HDL-C 浓度极高时，不良结果的风险增加。 目的 研究极高 HDL-C 水平 (>80 mg/dL) 与冠状动脉疾病 (CAD) 患者死亡率之间的关联，并调查已知 HDL-C 基因型与高 HDL-C 水平结果的关联。 设计、设置和参与者 这项前瞻性、多中心、队列研究， 2006 年至今在英国和 2003 年至今在佐治亚州亚特兰大进行的研究分别从英国生物库 (UKB) 和埃默里心血管生物库 (EmCAB) 招募 CAD 患者。未确诊 CAD 的患者被排除在研究之外。数据分析于2020年5月10日至2021年4月28日进行。暴露高HDL-C水平（>80 mg/dL）。主要结果和措施主要结果是全因死亡。次要结局是心血管死亡。 结果 本研究共纳入了来自 UKB 的 14 478 名参与者（平均 [SD] 年龄，62.1 [5.8] 岁；11 034 名男性 [76.2%]）和来自 EmCAB 的 5467 名参与者（平均 [SD] 年龄，63.8 [12.3] 岁；3632 名男性 [66.4%]）。 UKB 的中位随访时间为 8.9（IQR，8.0-9.7）年，EmCAB 的中位随访时间为 6.7（IQR，4.0-10.8）年，观察到与结果的 U 形关联，与中等值的 HDL-C 水平的患者相比，HDL-C 水平低和极高的患者风险较高。极高的 HDL-C 水平 (>80 mg/dL) 与全因死亡风险增加相关（风险比 [HR]，1.96； 95% CI，1.42-2.71；调整混杂因素后，与 UKB 中 HDL-C 水平在 40 至 60 mg/dL 范围内的患者相比，P < .001）和心血管死亡（HR，1.71；95% CI，1.09-2.68；P = .02）。这些结果在 EmCAB 中得到了重复。在对 UKB 内的 HDL-C 遗传风险评分进行调整后，这些关联仍然存在。敏感性分析表明，在 UKB，HDL-C 极高组中男性的全因死亡率风险高于女性（HR.2.63；95% CI，1.75-3.95；P< .001 vs HR，1.39；95% CI. 0.82-2.35；P = .23）。 结论和相关性 该队列研究的结果表明HDL-C 水平非常高 矛盾的是，它与 CAD 患者较高的死亡风险相关。这种关联独立于与高 HDL-C 水平相关的常见多态性。
IMPORTANCE Previous studies have shown lower cardiovascular risk with higher high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high HDL-C concentrations.OBJECTIVE To study the association between very high HDL-C levels (>80 mg/dL) and mortality in patients with coronary artery disease (CAD) and to investigate the association of known HDL-C genotypes with high HDL-C level outcomes.DESIGN, SETTING, AND PARTICIPANTS This prospective, multicenter, cohort study, conducted from 2006 to present in the UK and from 2003 to present in Atlanta, Georgia, recruited patients with CAD from the UK Biobank (UKB) and the Emory Cardiovascular Biobank (EmCAB), respectively. Patients without confirmed CAD were excluded from the study. Data analyses were conducted from May 10, 2020, to April 28, 2021.EXPOSURE High HDL-C levels (>80 mg/dL).MAIN OUTCOMES AND MEASURES The primary outcome was all-cause death. The secondary outcome was cardiovascular death.RESULTS A total of 14 478 participants (mean [SD] age, 62.1 [5.8] years; 11 034 men [76.2%]) from the UKB and 5467 participants (mean [SD] age, 63.8 [12.3] years; 3632 men [66.4%]) from the EmCAB were included in the study. Over a median follow-up of 8.9 (IQR, 8.0-9.7) years in the UKB and 6.7 (IQR, 4.0-10.8) years in the EmCAB, a U-shaped association with outcomes was observed with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (>80 mg/dL) were associated with increased risk of all-cause death (hazard ratio [HR), 1.96; 95% CI, 1.42-2.71; P < .001) and cardiovascular death (HR, 1.71; 95% CI, 1.09-2.68; P = .02) compared with those with HDL-C levels in the range of 40 to 60 mg/dL in the UKB after adjustment for confounding factors. These results were replicated in the EmCAB. These associations persisted after adjustment for the HDL-C genetic risk score within the UKB. Sensitivity analyses demonstrated that the risk of all-cause mortality in the very high HDL-C group was higher among men than women in the UKB (HR. 2.63; 95% CI, 1.75-3.95; P< .001 vs HR, 1.39; 95% CI. 0.82-2.35; P = .23).CONCLUSIONS AND RELEVANCE Results of this cohort study suggest that very high HDL-C levels are paradoxically associated with higher mortality risk in individuals with CAD. This association was independent of the common polymorphisms associated with high HDL-C levels.