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Low-density lipoprotein cholesterol and all-cause mortality: findings from the China health and retirement longitudinal study.

ABSTRACT: OBJECTIVES:To investigate the relationship between low-density lipoprotein cholesterol (LDL-C) and all-cause mortality among middle-aged and elderly Chinese population. DESIGN:Prospective cohort study. SETTING:This study used data from the China Health and Retirement Longitudinal Study. PARTICIPANTS:Middle-aged and elderly participants with complete data were enrolled for a 4-year follow-up of total mortality and plasma levels of LDL-C, including 4981 male respondents and 5529 female respondents. RESULTS:During a 4-year follow-up, there were 305 and 219 deaths in men and women, respectively. Compared with the first quintile (Q1) of LDL-C, the adjusted HRs (95% CIs) were 0.818 (0.531 to 1.260) for Q2, 0.782 (0.507 to 1.208) for Q3, 0.605 (0.381 to 0.962) for Q4 and 0.803 (0.506 to 1.274) for Q5 in men. The results from restricted cubic spine (RCS) showed that when the 20th percentile of LDL-C levels (84 mg/dL) was used as the reference, a lower LDL-C concentration (<84 mg/dL) was associated with a higher 4-year all-cause mortality risk. By contrast, both quintile analysis and RCS analysis did not show a statistically significant association in women. CONCLUSIONS:Compared with moderately elevated LDL-C (eg, 117-137 mg/dL), a lower plasma level of LDL-C (eg, ?84 mg/dL) was associated with an increased risk of 4-year all-cause mortality in middle-aged and elderly Chinese men. The results suggest the potential harmful effect of a quite low level of LDL-C on total mortality.

SUBMITTER: Zhou L

PROVIDER: S-EPMC7430481 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesThe relationship between HDL cholesterol and all-cause mortality in patients with kidney disease is not clear. We sought to characterize the relationship of HDL cholesterol and risk of death and examine the association by eGFR levels.Design, setting, participants, & measurementsWe built a cohort of 1,764,986 men who were United States veterans with at least one eGFR between October of 2003 and September of 2004 and followed them until September of 2013 or death.ResultsPatients with low HDL cholesterol and low eGFR had a higher burden of comorbid illnesses. Over a median of 9.1 years (interquartile range, 7.7-9.4 years), 26,247 (40.1%), 109,222 (32.3%), 152,625 (29.2%), 113,785 (28.5%), and 139,803 (31.8%) participants with HDL cholesterol ?25, >25 to <34, ?34 to ?42, >42 to <50, and ?50 mg/dl died. In adjusted survival models, compared with the referent group of patients with low HDL cholesterol (?25 mg/dl), intermediate HDL cholesterol levels (>25 to <34, ?34 to ?42, and >42 to <50 mg/dl) were associated with lower risk of death across all levels of eGFR. The lower risk was partially abrogated in those with high HDL cholesterol (?50 mg/dl), and the risk of death was similar to the referent category among those with eGFR<30 or ?90 ml/min per 1.73 m2. Analysis by HDL cholesterol deciles and spline analyses suggest that the relationship between HDL cholesterol and death follows a U-shaped curve. There was a significant interaction between eGFR and HDL cholesterol in that lower eGFR attenuated the salutary association of HDL cholesterol and risk of death (P for interaction <0.01). Presence of coronary artery disease attenuated the lower risk of high HDL cholesterol and all-cause mortality in those with eGFR?60 ml/min per 1.73 m2 (P for interaction <0.05).ConclusionsOur results show a U-shaped relationship between HDL cholesterol and risk of all-cause mortality across all eGFR categories. The risk is modified by eGFR and cardiovascular disease.

Project description:ImportanceLow-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor for atherosclerotic cardiovascular disease. It is unclear whether the percentage LDL-C lowering with pharmacotherapies differs on the basis of baseline LDL-C levels.ObjectiveTo evaluate the association between baseline LDL-C levels and the percentage LDL-C reduction with a statin, ezetimibe, and a PCSK9 inhibitor.Design, setting, and participantsThis secondary exploratory study analyzed data from 3 randomized placebo-controlled clinical trials (Aggrastat to Zocor-Thrombolysis in Myocardial Infarction 21 [A to Z-TIMI 21], Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT], and Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]) of lipid-lowering therapies (statin, ezetimibe, and a PCSK9 inhibitor) and included participants with atherosclerotic cardiovascular disease. Analyses took place form April to October 2020.InterventionsIn A to Z-TIMI 21, 1:1 randomization to simvastatin, 40 mg, daily for 30 days followed by 80 mg daily thereafter vs placebo for 4 months followed by simvastatin, 20 mg, daily thereafter. In IMPROVE-IT, 1:1 randomization to ezetimibe, 10 mg, daily plus simvastatin, 40 mg, daily vs placebo plus simvastatin, 40 mg, daily. In FOURIER, 1:1 randomization to evolocumab, 140 mg, every 2 weeks or 420 mg monthly vs matching placebo.Main outcomes and measuresThe percentage LDL-C reduction at either 1 month (A to Z-TIMI 21, IMPROVE-IT) or 3 months (FOURIER) as a function of baseline LDL-C level. Data were modeled using a generalized linear regression model.ResultsA total of 3187 patients from A to Z-TIMI 21, 10 680 patients from IMPROVE-IT, and 25 847 patients from FOURIER were analyzed. There was a higher percentage reduction in LDL-C levels with evolocumab in patients with lower baseline LDL-C levels, ranging from 59.4% (95% CI, 59.1%-59.8%) in patients with a baseline LDL-C level of 130 mg/dL to 66.1% (95% CI, 65.6%-66.6%) in patients with a baseline LDL-C level of 70 mg/dL (P < .001). In contrast, across the same range of baseline LDL-C level, there was a more modest difference for simvastatin (44.6% [95% CI, 43.9%-45.2%] vs 47.8% [95% CI, 46.4%-49.2%]; P < .001) and minimal difference with ezetimibe (25.0% [95% CI, 23.3%-26.6%] vs 26.2% [95% CI, 24.2%-28.1%]; P = .007).Conclusions and relevanceThe percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels and is 6.6% greater for PCSK9 inhibition. These data are encouraging for the use of intensive LDL-C-lowering therapy even for patients with lower LDL-C levels.

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Low-density lipoprotein cholesterol and all-cause mortality: findings from the China health and retirement longitudinal study.

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