Cardiovascular

Lipoprotein(a) and Risk Stratification for Atherosclerotic Cardiovascular Disease Across the Cardiovascular-Kidney-Metabolic Continuum.

Fang Y, Pei X, et al. • Journal of the American Heart Association • 2026

PubMed 42924847 DOI 10.1161/JAHA.126.051179
TL;DR

Elevated Lp(a) was associated with higher incident ASCVD risk across the cardiovascular-kidney-metabolic continuum, and although relative associations were broadly consistent across CKM stages, absolute risk increments associated with elevated Lp(a) were greater at more advanced CKM stages, supporting integration of Lp(a) into CKM-based risk stratification for primary prevention.

Key Findings

Results

Elevated Lp(a) (≥125 nmol/L) was independently associated with higher risk of incident ASCVD in UK Biobank participants free of clinical cardiovascular disease at baseline.

  • Cohort: 333,321 UK Biobank participants classified into CKM stages 0 to 3; median follow-up 15.3 years; 17,581 incident ASCVD events (coronary artery disease or ischemic stroke).
  • After adjustment for demographic, socioeconomic and lifestyle factors, LDL cholesterol, medications, and CKM stage: HR 1.31 (95% CI, 1.25-1.36).
  • Cox proportional hazards models were used to estimate hazard ratios.
Results

Risk increased progressively across combined CKM-Lp(a) categories, with the highest risk in participants with CKM stage 3 and elevated Lp(a).

  • Compared with CKM stage 0 and lower Lp(a), CKM stage 3 with elevated Lp(a) had HR 3.43 (95% CI, 2.74-4.31).
  • Joint analyses combined CKM stage and Lp(a) category.
Results

Ten-year absolute ASCVD risk varied widely across combined CKM-Lp(a) categories.

  • Ten-year ASCVD risk ranged from 0.64% to 16.30%.
  • Absolute risks were estimated using Kaplan-Meier methods.
Results

The absolute 10-year risk difference associated with elevated Lp(a) increased with advancing CKM stage, even though relative associations were broadly consistent across stages.

  • Absolute risk difference associated with elevated Lp(a) rose from 0.23% in stage 0 to 2.20% in stage 3.
  • Relative associations were described as broadly consistent across CKM stages.
Conclusions

The authors conclude that Lp(a) provides complementary risk stratification beyond CKM staging and support integrating it into CKM-based primary prevention risk assessment.

  • Larger absolute risk increments at advanced CKM stages suggest greater potential clinical relevance of Lp(a) in those groups.
  • Findings pertain to primary prevention in participants without clinical cardiovascular disease at baseline.

What This Means

This study used data from over 333,000 UK Biobank participants who did not have cardiovascular disease at the start and followed them for about 15 years. Participants were grouped by cardiovascular-kidney-metabolic (CKM) health stage, from 0 to 3, which reflects the combined burden of heart, kidney and metabolic problems such as obesity, diabetes and kidney disease. The researchers looked at whether high levels of lipoprotein(a), or Lp(a), a cholesterol-carrying particle largely determined by genetics, were linked to later heart attacks, coronary disease or ischemic stroke. High Lp(a) (125 nmol/L or above) was linked to about a 31% higher risk of these events, even after accounting for LDL cholesterol, lifestyle, medications and CKM stage. The proportional increase in risk was similar across CKM stages, but because people at later stages already have higher baseline risk, high Lp(a) added more in absolute terms: about 0.23 percentage points over 10 years in stage 0 versus 2.20 percentage points in stage 3. People with both stage 3 CKM and high Lp(a) had about 3.4 times the risk of those with stage 0 and lower Lp(a). This research suggests that measuring Lp(a) could help refine who is at highest risk of heart disease and stroke, particularly among people who already have more advanced CKM conditions. As an observational study in a largely UK-based cohort, it shows association rather than proof that lowering Lp(a) would prevent events.

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Citation

Fang Y, Pei X, Huang S, Zhang H, Li M, Zhang H, et al.. (2026). Lipoprotein(a) and Risk Stratification for Atherosclerotic Cardiovascular Disease Across the Cardiovascular-Kidney-Metabolic Continuum.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.126.051179