Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (S.M.A., A.R., D.K.M., J.A.D., S.M.G., J.D.B., A.K.).
Veteran's Affairs North Texas Medical Center, Dallas (S.M.A., S.M.G.).
Circulation. 2018 Nov 20;138(21):2315-2325. doi: 10.1161/CIRCULATIONAHA.118.034273.
BACKGROUND: The associations of low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) and coronary heart disease mortality in an exclusively low estimated 10-year risk group are not well delineated. We sought to determine the long-term associations of various LDL-C and non-high-density lipoprotein cholesterol (HDL-C) thresholds and CVD and coronary heart disease mortality in a large, low 10-year risk cohort. METHODS: The study sample included participants of the CCLS (Cooper Center Longitudinal Study) without a history of CVD or diabetes mellitus and defined as low risk (<7.5%) for 10-year atherosclerotic CVD events at baseline based on Pooled Cohort Risk Assessment Equations. The associations of fasting LDL-C and non-HDL-C with CVD mortality were tested with Cox proportional hazards models. RESULTS: In 36 375 participants (72% men, median age 42) followed for a median of 26.8 years, 1086 CVD and 598 coronary heart disease deaths occurred. Compared with LDL-C <100 mg/dL, LDL-C categories 100 to 129 mg/dL, 130 to 159 mg/dL, 160 to 189.9 mg/dL, and ≥190 mg/dL were associated with a significantly higher risk of CVD death, with hazard ratios of 1.4 (95% CI, 1.1-1.7), 1.3 (95% CI, 1.1-1.6), 1.9 (95% CI, 1.5-2.4), and 1.7 (95% CI, 1.3-2.3), and mean reductions in years free of CVD death of 1.8, 1.1, 4.3, and 3.9, respectively. After adjustment for atherosclerotic CVD risk factors, LDL-C categories 160 to 189 mg/dL and ≥190 mg/dL remained independently associated with CVD mortality, with hazard ratios of 1.7 (95% CI, 1.4-2.2) and 1.5 (95% CI, 1.2-2.1), respectively. In multivariable-adjusted models using non-HDL-C <130 mg/dL as the reference, non-HDL-C 160 to 189 mg/dL, 190 to 219 mg/dL, and ≥220 mg/dL were significantly associated with CVD death, with hazard ratios of 1.3 (95% CI, 1.1-1.6), 1.8 (95% CI, 1.4-2.2), and 1.5 (95% CI, 1.2-2.0), respectively. Restricting the cohort to those with 10-year risk <5% did not diminish the associations of LDL-C and non-HDL-C with CVD mortality. CONCLUSIONS: In a low 10-year risk cohort with long-term follow-up, LDL-C and non-HDL-C ≥160 mg/dL were independently associated with a 50% to 80% increased relative risk of CVD mortality. These findings may have implications for future cholesterol treatment paradigms.
背景：在一个专门评估的低估计 10 年风险人群中，低密度脂蛋白胆固醇 (LDL-C) 与心血管疾病 (CVD) 和冠心病死亡率之间的关联尚未得到很好的描述。我们旨在确定在一个大型的低 10 年风险队列中，各种 LDL-C 和非高密度脂蛋白胆固醇 (HDL-C) 阈值与 CVD 和冠心病死亡率的长期关联。
方法：研究样本包括没有 CVD 或糖尿病病史的 CCLS（库珀中心纵向研究）参与者，并且根据 Pooled Cohort Risk Assessment Equations，基线时 10 年动脉粥样硬化性 CVD 事件的风险低（<7.5%）。使用 Cox 比例风险模型测试空腹 LDL-C 和非 HDL-C 与 CVD 死亡率的关联。
结果：在 36375 名参与者（72%为男性，中位年龄 42 岁）中，中位随访时间为 26.8 年，发生了 1086 例 CVD 和 598 例冠心病死亡。与 LDL-C<100mg/dL 相比，LDL-C 水平为 100-129mg/dL、130-159mg/dL、160-189.9mg/dL 和≥190mg/dL 与 CVD 死亡风险显著增加相关，风险比分别为 1.4（95%CI，1.1-1.7）、1.3（95%CI，1.1-1.6）、1.9（95%CI，1.5-2.4）和 1.7（95%CI，1.3-2.3），无 CVD 死亡的年数分别平均减少 1.8、1.1、4.3 和 3.9。在校正动脉粥样硬化性 CVD 危险因素后，LDL-C 水平为 160-189mg/dL 和≥190mg/dL 仍与 CVD 死亡率独立相关，风险比分别为 1.7（95%CI，1.4-2.2）和 1.5（95%CI，1.2-2.1）。在使用非 HDL-C<130mg/dL 作为参考的多变量调整模型中，非 HDL-C 水平为 160-189mg/dL、190-219mg/dL 和≥220mg/dL 与 CVD 死亡显著相关，风险比分别为 1.3（95%CI，1.1-1.6）、1.8（95%CI，1.4-2.2）和 1.5（95%CI，1.2-2.0）。将队列限制在 10 年风险<5%的人群中，并不会降低 LDL-C 和非 HDL-C 与 CVD 死亡率之间的关联。
结论：在一个低 10 年风险且随访时间较长的队列中，LDL-C 和非 HDL-C≥160mg/dL 与 CVD 死亡率增加 50%-80%独立相关。这些发现可能对未来的胆固醇治疗模式产生影响。
Circ Cardiovasc Qual Outcomes. 2016-5
Front Med (Lausanne). 2025-8-12
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