Elevated Lp(a) associated with CAD in individuals without a family history of CVD

Lipoprotein(a) and Coronary Artery Disease Risk Without a Family History of Heart Disease

Literature - Finneran P, Pampana A, Khetarpal SA et al., - J Am Heart Assoc. 2021 Feb;10(5):e017470. doi: 10.1161/JAHA.120.017470.

Introduction and methods

Elevated lipoprotein(a) (Lp[a]) is associated with increased risk for coronary artery disease (CAD) [1]. Lp(a) is a heritable risk factor and a family history of premature atherosclerotic CVD (ASCVD) is listed as an indication for Lp(a) assessment for primary prevention in American cholesterol guidelines [2]. However, the risk of incident CAD in individuals with elevated Lp(a) without a family history of CVD is unknown. This study investigated the incident risk of CAD in participants from the UK Biobank with and without a family history of CVD.

The UK Biobank is a prospective, observational cohort of ~500 000 individuals aged 40 to 69 years. This study analyzed data from 153 228 participants without CAD and with measured Lp(a) at baseline and with a follow-up time of <9 years. Mean age was 58.4 years (SD: 7.9 years), 52.2% were female and the median follow-up was 8.2 years (IQR 7.8-8.6 years). The primary outcome was incident CAD. Risk of incident CAD conferred by Lp(a) was estimated and adjusted for age, sex, self-reported ethnicity, T2DM, smoking status, LDL-c, and statin or ezetimibe use. Incident CAD risk in those without a family history of CVD in a sibling or parent was compared with those with a family history of CVD. The secondary outcome was risk of incident ASCVD, defined as CAD, peripheral arterial disease, or ischemic stroke.

Main results

  • HR for incident CAD per 50 nmol/L Lp(a) was 1.18 (95%CI 1.11-1.26, P<0.001) in participants with a family history of CVD and 1.15 (95%CI 1.13-1.17, P<0.001) in those without a family history of CVD (P for interaction=0.73).
  • HR for incident CAD associated with Lp(a) >150 nmol/L, compared with Lp(a) <150 nmol/L, was 2.00 (95%CI 1.46-2.74, P<0.001) in those with a family history and 1.68 (95%CI 1.55-1.82, P<0.001) in those without a family history (P for interaction=0.68).
  • HR for incident ACSVD per 50 nmol/L Lp(a) was 1.15 (95%CI 1.09-1.21, P<0.001) in those with a family history and 1.12 (95%CI 1.10-1.14, P<0.001) in those without a family history (P for interaction=0.66).

Conclusion

Elevated Lp(a) is associated with an increased risk for incident CAD in individuals without a family history of CVD. The authors state that 'Lp(a) measurement may be beneficial in refining CAD risk in primary prevention patients without a family history of heart disease'.

References

1. Tipping RW, Ford CE, Simpson LM, Walldius G, Jungner I, Folsom AR, Chambless L, Panagiotakos D, Pitsavos C, Chrysohoou C, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302:412–423.

2. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/ PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1046–e1081.

Find this article online at J Am Heart Assoc.

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