Search

Background Lipoprotein(a) [Lp(a)] has been implicated in the etiology of aortic valve stenosis. Although Lp(a) is strongly associated with the presence of aortic valve calcium (AVC), there are no data evaluating the relationship of Lp(a) with AVC incidence and AVC progression. Purpose To assess whether high Lp(a) levels are associated with AVC incidence and progression. Methods In 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men) for whom Lp(a) measurements were available, non-enhanced cardiac CT imaging was performed at baseline and after a median follow-up of 14.0 [13.9–14.2] years. AVC incidence was defined as an AVC score >0 on the second scan, in absence of AVC on the first scan. We performed logistic regression analyses to evaluate the relationship of Lp(a) with AVC incidence and linear regression analyses to assess the relationship between Lp(a) and AVC progression. All analyses were corrected for age, sex, body mass index, smoking, non-high-density lipoprotein cholesterol, use of lipid-lowering medication, and hypertension. Additionally, we analyzed the progression conditional on the baseline AVC-score. Results Of the 702 (76.1%) individuals without AVC at baseline, 415 (59.1%) showed incident AVC at follow-up. The 220 (23.9%) individuals with AVC on baseline had a median AVC score of 52 [15–131], with a median yearly progression of 13 [5–38]. Lp(a) concentration was independently associated with AVC incidence (OR 1.32 for each 105 nmol/L Lp(a) increase; 95% CI: 1.03–1.68), but not with AVC progression (β −4.3 AU/year for each 105 nmol/L Lp(a) increase; 95% CI: −12.3–3.7). Conclusions Lp(a) is associated with AVC incidence but not AVC progression, suggesting that Lp(a)-lowering interventions may be futile after AVC has been established. Future studies should focus on whether Lp(a) lowering interventions can prevent the development of AVC in high-risk individuals. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Rotterdam Study is supported by Erasmus MC and Erasmus University Rotterdam and the Netherlands Organization for Scientific Research

Background Aortic valve calcium (AVC) is an important hallmark of aortic valve stenosis, which is the most common valvular heart disease in the Western world. Studies suggesting an important role for lipoprotein(a) [Lp(a)] in the etiology of AVC are accumulating, yet population-based evidence is scarce. Therefore, we investigated the association of Lp(a) with the presence of AVC in two large cohorts. Methods A total of 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3), and 859 asymptomatic persons from the Amsterdam Medical Center outpatient clinic for familial premature (non-valvular) atherosclerosis (57%women, mean age=45.9±11.6) underwent blood sampling to determine serum Lp(a) and non-enhanced cardiac CT-scan to assess AVC. We combined both cohorts and investigated the association of Lp(a) with the presence and amount of AVC using logistic and linear regression models, adjusting for age, sex, smoking, body mass index, non-high density lipoprotein cholesterol and use of antihypertensive medication. Results Out of a total of 3271 subjects with an average age of 63.4±7.98, AVC was present in 844 (25.8%) individuals. Higher levels of Lp(a) were associated with the presence of AVC, independent of age, sex and cardiovascular risk factors [Odds ratio (OR) per 1-SD increase in Lp(a): 1.39 (95% CI:1.27; 1.51). In persons with AVC, a higher level of Lp(a) was also related to larger volume of AVC [β per 1-SD increase in Lp(a): 0.76 (95% CI:1.27; 1.51)]. All findings were similar across both cohorts. Conclusion Lp(a) is a prominent and independent marker of the presence and amount of AVC in the general population. Future studies investigating the effect of Lp(a) lowering on the progression of AVC are warranted. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): NESTOR program for geriatric research, the Netherlands Heart Foundation, the Netherlands Organization for Scientific Research, the Health Research and Development Council (28-2975 and 97-1-364), and the Municipality of Rotterdam