Lp(a) (Lipoprotein[a]) Concentrations and Incident Atherosclerotic Cardiovascular Disease: New Insights From a Large National Biobank

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 41; no. 1; pp. 465 - 474
• Main Authors: Patel, Aniruddh P., Wang, Minxian, Pirruccello, James P., Ellinor, Patrick T., Ng, Kenney, Kathiresan, Sekar, Khera, Amit V.
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01-01-2021; American Heart Association, Inc
• Subjects: Adult; Aged; Atherosclerosis - blood; Atherosclerosis - diagnosis; Atherosclerosis - epidemiology; Atherosclerosis - prevention & control; Biological Specimen Banks; Biomarkers - blood; Female; Heart Disease Risk Factors; Humans; Incidence; Lipoprotein(a) - blood; Male; Middle Aged; Primary Prevention; Prognosis; Race Factors; Risk Assessment; Secondary Prevention; Time Factors; United Kingdom; United Kingdom; atherosclerosis; cardiovascular disease; secondary prevention; lipoprotein(a); myocardial infarction
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.120.315291

OBJECTIVE:Lipoprotein(a) concentrations are associated with atherosclerotic cardiovascular disease (ASCVD), and new therapies that enable potent and specific reduction are in development. In the largest study conducted to date, we address 3 areas of uncertainty(1) the magnitude and shape of ASCVD risk conferred across the distribution of lipoprotein(a) concentrations; (2) variation of risk across racial and clinical subgroups; (3) clinical importance of a high lipoprotein(a) threshold to guide therapy.
APPROACH AND RESULTS:Relationship of lipoprotein(a) to incident ASCVD studied in 460 506 middle-aged UK Biobank participants. Over a median follow-up of 11.2 years, incident ASCVD occurred in 22 401 (4.9%) participants. Median lipoprotein(a) concentration was 19.6 nmol/L (25th–75th percentile 7.6–74.8). The relationship between lipoprotein(a) and ASCVD appeared linear across the distribution, with a hazard ratio of 1.11 (95% CI, 1.10–1.12) per 50 nmol/L increment. Substantial differences in concentrations were noted according to race—median values for white, South Asian, black, and Chinese individuals were 19, 31, 75, and 16 nmol/L, respectively. However, risk per 50 nmol/L appeared similar—hazard ratios of 1.11, 1.10, and 1.07 for white, South Asian, and black individuals, respectively. A high lipoprotein(a) concentration defined as ≥150 nmol/L was present in 12.2% of those without and 20.3% of those with preexisting ASCVD and associated with hazard ratios of 1.50 (95% CI, 1.44–1.56) and 1.16 (95% CI, 1.05–1.27), respectively.
CONCLUSIONS:Lipoprotein(a) concentrations predict incident ASCVD among middle-aged adults within primary and secondary prevention contexts, with a linear risk gradient across the distribution. Concentrations are variable across racial subgroups, but the associated risk appears similar.