Association of low-density lipoprotein cholesterol levels with the risk of mortality and cardiovascular events: A meta-analysis of cohort studies with 1,232,694 participants.
Level 3 - non-randomized controlled study
Meta-analysis of observational cohort studies
PubMed 36482567 · doi:10.1097/MD.0000000000032003
What was done
Authors conducted a systematic review and meta-analysis of 20 cohort studies (searching PubMed, Embase, Cochrane Library, and Web of Science through April 7, 2021) comprising 1,232,694 adults. The analysis evaluated the association between categorized LDL-C levels (< 70, 130–159, and ≥ 160 mg/dL vs. reference 70–129 mg/dL) and all-cause mortality, cardiovascular disease (CVD) death, coronary heart disease (CHD) death, and total CVD events using pooled relative risks (RR) and 95% confidence intervals (CI).
What was found
Compared to reference LDL-C (70–129 mg/dL): - LDL-C ≥ 160 mg/dL was associated with higher risks of all-cause mortality (RR: 1.34, 95% CI: 1.00–1.80), CVD death (RR: 1.79, 95% CI: 1.26–2.54), CHD death (RR: 2.03, 95% CI: 1.36–3.03), and CVD events (RR: 1.70, 95% CI: 1.35–2.14). - LDL-C 130–159 mg/dL was associated with higher CVD risk (RR: 1.26, 95% CI: 1.08–1.47). - LDL-C < 70 mg/dL showed no association with all-cause mortality or CVD events.
Why it matters
This large meta-analysis reinforces guidelines targeting LDL-C reduction below 130 mg/dL and shows no observational association between low LDL-C (< 70 mg/dL) and increased all-cause mortality.
Limits
The findings are derived entirely from observational cohort studies susceptible to unmeasured confounding and reverse causation. The abstract does not report individual study follow-up durations, adjustment for lipid-lowering therapies, or sub-analyses for very low LDL-C thresholds (e.g., < 40 or 50 mg/dL).
Cited by
- supports Elevated LDL cholesterol levels are associated with a 10% to 30% increased risk of mortality.