|Title||Association Between Cumulative Low-Density Lipoprotein Cholesterol Exposure During Young Adulthood and Middle Age and Risk of Cardiovascular Events.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Zhang Y, Pletcher MJ, Vittinghoff E, Clemons AM, Jacobs DR, Allen NB, Alonso A, Bellows BK, Oelsner EC, Hazzouri AZeki Al, Kazi DS, de Ferranti SD, Moran AE|
|Date Published||2021 12 01|
|Keywords||Adolescent, Adult, Cardiovascular Diseases, Cholesterol, LDL, Female, Follow-Up Studies, Humans, Hypolipidemic Agents, Incidence, Male, Middle Aged, Primary Prevention, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States, Young Adult|
Importance: Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease (CVD). Most observational studies on the association between LDL-C and CVD have focused on LDL-C level at a single time point (usually in middle or older age), and few studies have characterized long-term exposures to LDL-C and their role in CVD risk.
Objective: To evaluate the associations of cumulative exposure to LDL-C, time-weighted average (TWA) LDL-C, and the LDL-C slope change during young adulthood and middle age with incident CVD later in life.
Design, Setting, and Participants: This cohort study analyzed pooled data from 4 prospective cohort studies in the US (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis). Participants were included if they had 2 or more LDL-C measures that were at least 2 years apart between ages 18 and 60 years, with at least 1 of the LDL-C measures occurring during middle age at 40 to 60 years. Data from 1971 to 2017 were collected and analyzed from September 25, 2020, to January 10, 2021.
Exposures: Cumulative exposure to LDL-C, TWA LDL-C, and LDL-C slope from age 18 to 60 years.
Main Outcomes and Measures: Incident coronary heart disease (CHD), ischemic stroke, and heart failure (HF).
Results: A total of 18 288 participants were included in this study. These participants had a mean (SD) age of 56.4 (3.7) years and consisted of 10 309 women (56.4%). During a median follow-up of 16 years, 1165 CHD, 599 ischemic stroke, and 1145 HF events occurred. In multivariable Cox proportional hazards regression models that adjusted for the most recent LDL-C level measured during middle age and for other CVD risk factors, the hazard ratios for CHD were as follows: 1.57 (95% CI, 1.10-2.23; P for trend = .01) for cumulative LDL-C level, 1.69 (95% CI, 1.23-2.31; P for trend <.001 for="" twa="" ldl-c="" level="" and="" ci="" p="" trend="" slope.="" no="" association="" was="" found="" between="" any="" of="" the="" variables="" ischemic="" stroke="" or="" hf.="">
Conclusions and Relevance: This cohort study showed that cumulative LDL-C and TWA LDL-C during young adulthood and middle age were associated with the risk of incident CHD, independent of midlife LDL-C level. These findings suggest that past levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic CVD.
|Alternate Journal||JAMA Cardiol|
|PubMed Central ID||PMC8459309|
|Grant List||R01 HL107475 / HL / NHLBI NIH HHS / United States |
K24 HL148521 / HL / NHLBI NIH HHS / United States
K23 HL130627 / HL / NHLBI NIH HHS / United States
R21 HL129924 / HL / NHLBI NIH HHS / United States
R01 HL141823 / HL / NHLBI NIH HHS / United States