Finding very high lipoprotein(a): the need for routine assessment

Abstract

Aims To validate the reported increased atherosclerotic cardiovascular disease (ASCVD) risk associated with very high lipoprotein(a) [Lp(a)] and to investigate the impact of routine Lp(a) assessment on risk reclassification. Methods and results We performed a cross-sectional case-control study in the Amsterdam UMC, a tertiary hospital in The Netherlands. All patients in whom a lipid blood test was ordered between October 2018 and October 2019 were included. Individuals with Lp(a) >99th percentile were age and sex matched to individuals with Lp(a) ≤20th percentile. We computed odds ratios (ORs) for myocardial infarction (MI) and ASCVD using multivariable logistic regression adjusted for age, sex, and systolic blood pressure. Furthermore, we assessed the additive value of Lp(a) to established ASCVD risk algorithms. Lipoprotein(a) levels were determined in 12 437 individuals, out of whom 119 cases [Lp(a) >99th percentile; >387.8 nmol/L] and 119 matched controls [Lp(a) ≤20th percentile; ≤7 nmol/L] were included. Mean age was 58 ± 15 years, 56.7% were female, and 30.7% had a history of ASCVD. Individuals with Lp(a) levels >99th percentile had an OR of 2.64 for ASCVD [95% confidence interval (CI) 1.45–4.89] and 3.39 for MI (95% CI 1.56–7.94). Addition of Lp(a) to ASCVD risk algorithms led to 31% and 63% being reclassified into a higher risk category for Systematic Coronary Risk Evaluation (SCORE) and Second Manifestations of ARTerial disease (SMART), respectively. Conclusion The prevalence of ASCVD is nearly three-fold higher in adults with Lp(a) >99th percentile compared with matched subjects with Lp(a) ≤20th percentile. In individuals with very high Lp(a), addition of Lp(a) resulted in one-third of patients being reclassified in primary prevention, and over half being reclassified in secondary prevention.

Trends in testing and prevalence of elevated Lp(a) among patients with aortic valve stenosis

“…Although the prevalence rates at various cutoffs were not included, subjects with Lp (a) > 99th percentile (>387.8 nmol/L) had an OR of 2.64 for ASCVD and 3.39 for MI compared to those ≤20th percentile (≤7 nmol/L]. Addition of Lp(a) to ASCVD risk algorithms led to 31-63% being reclassified into higher risk categories by several accepted metrics, suggesting the measurement of Lp(a) levels can make a significant difference in clinical care [24]. Lp(a) testing costs ~$30-100 in the US, and 10-25 euros per sample in the EU.…”

Considerations for routinely testing for high Lp(a)

“…Considering Lp(a) is a likely causal and independent risk factor for ASCVD, novel ASCVD risk scores should implement Lp(a). As was shown previously, hazard ratios from observational studies can easily be implemented into established risk scores, such as SCORE and SMART [32]. When validated in external cohort data, this should be the first step.…”

“…In primary prevention, every 50 mg/dl Lp(a) increase translates to a hazard ratio of 1.16 for CVD mortality alone [16]. In fact, it was shown that incorporation of Lp (a) into the Systematic COronary Risk Evaluation (SCORE) risk algorithm in patients with Lp(a) >99 th percentile led to a 31% reclassification in primary prevention patients [32]. In secondary prevention, 63% of patients with very high Lp(a) were reclassified to a higher risk category of the Second Manifestations of ARTerial diseases (SMART) score [32].…”

Lp(a): a New Pathway to Target?

“…In secondary prevention patients, where there is a 10-year recurrence risk exceeding 20% [23], high Lp(a) levels have a major impact on absolute ASCVD risk. Sixty-three percent of patients is reclassified into a higher risk category of the SMART (Secondary Manifestations of ARTerial disease) risk score when Lp(a) levels are taken into account [24]. In addition, also primary prevention patients with very high Lp(a) levels could benefit from Lp(a) lowering.…”