Association of small, dense LDL-cholesterol concentration and lipoprotein particle characteristics with coronary heart disease: A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of observational studies for an etiologic/prognostic question
PubMed 33166340 · doi:10.1371/journal.pone.0241993
What was done
Authors systematically searched PubMed, MEDLINE, Web of Science, and EMBASE through February 2020 to evaluate associations between small, dense low-density lipoprotein (sdLDL) particle characteristics or sdLDL-cholesterol concentration (sdLDL-C) and incident coronary heart disease (CHD). Analyses pooled hazard ratios and odds ratios using random-effects meta-analysis across 21 studies (30,628 subjects, 5,693 incident CHD events; mean age 67 years, 53% men), comparing binary categories for sdLDL particle size (14 studies) and top versus bottom quartiles for sdLDL-C (8 studies).
What was found
Higher sdLDL particle and sdLDL-C levels were significantly associated with incident CHD. The pooled risk estimate for high versus low sdLDL particle categorization was 1.36 (95% CI: 1.21, 1.52) and for top versus bottom quartile of sdLDL-C was 1.07 (95% CI: 1.01, 1.12). Several studies suggested a dose-response relationship.
Why it matters
The findings confirm small, dense LDL particle characteristics and cholesterol content as markers of elevated CHD risk, supporting further evaluation of sdLDL as a therapeutic target.
Limits
The evidence is derived from observational cohorts with potential residual confounding. Exposure definitions differed (binary categorization for particle size vs. quartile comparisons for sdLDL-C) and different effect metrics (hazard ratios and odds ratios) were standardized together. The abstract provides no data on statistical heterogeneity, adjustments for standard lipid levels, or interventional trials demonstrating that lowering sdLDL reduces CHD events.
Cited by
- supports People with heart disease or higher heart disease risk tend to have a higher proportion of smaller, denser LDL particles, whereas healthier individuals have more large, buoyant LDL particles.