Lipoprotein(a) levels in a global population with established atherosclerotic cardiovascular disease

Abstract

Objective: Lipoprotein(a) (Lp(a)) is an important genetically determined risk factor for atherosclerotic vascular disease (ASCVD). With the development of Lp(a)-lowering therapies, this study sought to characterise patterns of Lp(a) levels in a global ASCVD population and identify racial, ethnic, regional and gender differences.

Methods: A multicentre cross-sectional epidemiological study to estimate the prevalence of elevated Lp(a) in patients with a history of myocardial infarction, ischaemic stroke or peripheral artery disease conducted at 949 sites in 48 countries in North America, Europe, Asia, South America, South Africa and Australia between April 2019 and July 2021. Low-density lipoprotein cholesterol (LDL-C) and Lp(a) levels were measured either as mass (mg/dL) or molar concentration (nmol/L).

Results: Of 48 135 enrolled patients, 13.9% had prior measurements of Lp(a). Mean age was 62.6 (SD 10.1) years and 25.9% were female. Median Lp(a) was 18.0 mg/dL (IQR 7.9-57.1) or 42.0 nmol/L (IQR 15.0-155.4). Median LDL-C was 77 mg/dL (IQR 58.4-101.0). Lp(a) in women was higher, 22.8 (IQR 9.0-73.0) mg/dL, than in men, 17.0 (IQR 7.1-52.2) mg/dL, p<0.001. Black patients had Lp(a) levels approximately threefold higher than white, Hispanic or Asian patients. Younger patients also had higher levels. 27.9% of patients had Lp(a) levels >50 mg/dL, 20.7% had levels >70 mg/dL, 12.9% were >90 mg/dL and 26.0% of patients exceeded 150 nmol/L.

Conclusions: Globally, Lp(a) is measured in a small minority of patients with ASCVD and is highest in black, younger and female patients. More than 25% of patients had levels exceeding the established threshold for increased cardiovascular risk, approximately 50 mg/dL or 125 nmol/L.

Keywords: atherosclerosis; global burden of disease; hyperlipidemias.

Figure 1

(A) Frequency of lipoprotein(a) (Lp(a)) measurements for patients whose values were measured in mg/dL. The fraction of patients with values f ≥70 and 90 mg/dL (21% and 13%, respectively) are indicated by vertical lines. (B) Frequency of Lp(a) measurements for patients whose values were measured in nmol/L. The fraction of patients whose values were equal or above the commonly used threshold of 150 nmol/L (26%) is indicated by a vertical line.

Figure 2

(A) Relationship between lipoprotein(a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C) measurements. The bar charts demonstrate the increase in LDL-C related to lipid content of Lp(a) particles. IQR are shown for each category, <10 mg/dL, IQR 57.6–98.0; 10–49 mg/dL, IQR 60.0–103.0; 50–99 mg/dL, IQR 61.9–103.1; 100–150 mg/dL, IQR 64.6–107.5; ≥150 mg/dL, IQR 66.0–108.3. (B) Relationship between age and Lp(a) levels. Patients in the youngest quintile for age tended to have higher levels than patients in the oldest quintile. IQR, age 18–54 years, IQR 8.0–62.6; 55–60, IQR 7.1–60.6; 61–66, IQR 8.0–59.5; 67–71, IQR 7.7–54.0; 72–90, IQR 8.0–50.2.