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Original paper

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Cholesterol & Heart Health

Long-term association of low-density lipoprotein cholesterol with cardiovascular mortality in individuals at low 10-year risk of atherosclerotic cardiovascular disease

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

DOI: 10.1161/circulationaha.118.034273

Publication date: January 7, 2019

Keywords: Cardiology and Cardiovascular Medicine Physiology (medical)

  • This large long-term study has shown that raised levels of LDL-C (and also non HDL-C) increases the risk of CVD mortality even in people with a low 10-year CVD risk.
  • A key strength of this study is that 36 375 individuals were followed-up for more than 2 decades.
  • Further work is still required to see if a lipid-lowering diet, lifestyle and pharmacological interventions will affect CVD outcomes in this low risk group of people with raised LDL-C and non-HDL-C.

In this US based study, 36 375 participants, from the Cooper Center Longitudinal Study (CCLS) cohort, with no history of CVD or diabetes mellitus and estimated to be of low 10-year CVD risk (< 7.5%), were included in a long-term assessment of the impact of raised LDL-C and non-HDL-C (defined as total cholesterol minus HDL cholesterol) on CVD mortality. Participants were only included if they had lipid measurements recorded during the 1978-1998 time period to minimise any impact from being on lipid lowering therapy which was more commonly used after this time.

Nearly three quarters of the participants (72%) were males with a median age of 42 years; they were followed-up over a median of 26.8 years and during this time 1086 CVD and 598 coronary heart disease deaths were recorded.

LDL-C and non-HDL-C of greater or equal to 160 mg/dL were found to be independently associated with an increase of 50% to 80% in relative risk of CVD mortality. This increased risk remained also in a subset of individuals with an estimated 5% 10-year CVD risk. Non-HDL-C appeared to be also important for long-term CVD risk in addition to LDL-C. It can be measured at no extra cost to LDL-C and is considered to be potentially a more robust prognostic marker. There were not enough women in the study to assess statistical differences in CVD mortality but generally similar patterns of elevated risk were observed with both sexes.

This study is of particular interest because of its large-scale, long-time follow-up and especially the fact that it focuses on low (10-year) CVD risk people. Much of the evidence for lipid management and CVD risk is in individuals at intermediate and high risk of CVD.

Although this observational study does not provide direct evidence that lowering LDL-C will improve outcomes in low CVD risk populations, it adds to the discussion to consider appropriate LDL-C thresholds for lipid lowering interventions in people who are estimated to be of low CVD risk. Further research is needed to define lipid lowering strategies in low CVD risk individuals with elevated LDL-C and non-HDL-C levels.