Center for Lipid Metabolomics and Division of Preventive Medicine Brigham and Women's Hospital Boston MA.
Harvard Medical School Boston MA.
J Am Heart Assoc. 2020 Sep;9(17):e016507. doi: 10.1161/JAHA.119.016507. Epub 2020 Aug 15.
Background High-density lipoprotein (HDL) cholesterol has inverse association with cardiovascular disease. HDL possesses anti-inflammatory properties in vitro, but it is unknown whether this may be protective in individuals with inflammation. Methods and Results The functional capacity of HDL to inhibit oxidation of oxidized low-density lipoprotein (ie, the HDL inflammatory index; HII) was measured at baseline and 12 months after random allocation to rosuvastatin or placebo in a nested case-control study of the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Evaluating Rosuvastatin) trial. There were 517 incident cases of cardiovascular disease and all-cause mortality compared to 517 age- and sex-matched controls. Multivariable conditional logistic regression was used to examine associations of HII with events. Median baseline HII was 0.54 (interquartile range, 0.50-0.59). Twelve months of rosuvastatin decreased HII by a mean of 5.3% (95% CI, -8.9% to -1.7%; =0.005) versus 1.3% (95% CI, -6.5% to 4.0%; =0.63) with placebo (=0.22 for between-group difference). HII had a nonlinear relationship with incident events. Compared with the reference group (HII 0.5-1.0) with the lowest event rates, participants with baseline HII ≤0.5 had significantly increased risk of cardiovascular disease/mortality (adjusted hazard ratio, 1.53; 95% CI, 1.06-2.21; =0.02). Furthermore, there was significant (=0.002) interaction for HDL particle number with HII, such that having more HDL particles was associated with decreased risk only when HDL was anti-inflammatory. Conclusions In JUPITER participants recruited on the basis of chronic inflammation, HII was associated with incident cardiovascular disease/mortality, with an optimal anti-inflammatory HII range between 0.5 and 1.0. This nonlinear relationship of anti-inflammatory HDL function with risk may account in part for the HDL paradox. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00239681.
高密度脂蛋白（HDL）胆固醇与心血管疾病呈负相关。HDL 在体外具有抗炎特性，但尚不清楚这是否对存在炎症的个体具有保护作用。
在 JUPITER（他汀类药物在预防中的应用理由：评估瑞舒伐他汀的干预）试验的巢式病例对照研究中，在随机分配至瑞舒伐他汀或安慰剂后 12 个月时，测量了 HDL 抑制氧化型低密度脂蛋白（即 HDL 炎症指数；HII）氧化的功能能力。与 517 例年龄和性别匹配的对照相比，有 517 例发生心血管疾病和全因死亡事件。多变量条件逻辑回归用于检查 HII 与事件的关联。中位基线 HII 为 0.54（四分位距，0.50-0.59）。瑞舒伐他汀治疗 12 个月平均降低 HII 5.3%（95%CI，-8.9%至-1.7%；=0.005），安慰剂组降低 1.3%（95%CI，-6.5%至 4.0%；=0.63）（=0.22 组间差异）。HII 与新发事件呈非线性关系。与事件发生率最低的参考组（HII 0.5-1.0）相比，基线 HII≤0.5 的参与者发生心血管疾病/死亡率的风险显著增加（校正后的危险比，1.53；95%CI，1.06-2.21；=0.02）。此外，HDL 颗粒数与 HII 之间存在显著交互作用（=0.002），即只有当 HDL 具有抗炎作用时，HDL 颗粒数增加与风险降低相关。
在基于慢性炎症招募的 JUPITER 参与者中，HII 与新发心血管疾病/死亡率相关，最佳抗炎 HII 范围在 0.5 至 1.0 之间。抗炎性 HDL 功能与风险的这种非线性关系可能部分解释了 HDL 悖论。
