Long-Term Association of Low-Density Lipoprotein Cholesterol with Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease: Results from the Cooper Center Longitudinal Study

Shuaib M Abdullah, Laura F. Defina, David Leonard, Carolyn E. Barlow, Nina B. Radford, Benjamin L. Willis, Anand K Rohatgi, Darren K McGuire, James A de Lemos, Scott M Grundy, Jarett D Berry, Amit Khera

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2315-2325
Number of pages11
JournalCirculation
Volume138
Issue number21
DOIs
StatePublished - Nov 20 2018

Keywords

  • long-term follow-up
  • low-density lipoprotein
  • primary prevention

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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