Lipoprotein(a), LDL-cholesterol, and hypertension: Predictors of the need for aortic valve replacement in familial hypercholesterolaemia

Leopoldo Pérez De Isla, Gerald F. Watts, Rodrigo Alonso, José Luis Díaz-Díaz, Ovidio Muñiz-Grijalvo, Daniel Zambón, Francisco Fuentes, Raimundo De Andrés, Teresa Padró, José López-Miranda, Pedro Mata

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Aims: Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH. Methods and results: SAFEHEART is a long-term prospective cohort study of a population with FH and non-affected relatives (NAR). We analysed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3712 with FH; 1310 NAR). Fifty patients with FH (1.48%) and 3 NAR (0.27%) required AVR [odds ratio 5.71; 95% confidence interval (CI): 1.78-18.4; P = 0.003] after a mean follow-up of 7.48 (3.75) years. The incidence of AVR was significantly higher in patients with FH (log-rank 5.93; P = 0.015). Cox regression analysis demonstrated an association between FH and AVR (hazard ratio: 3.89; 95% CI: 1.20-12.63; P = 0.024), with older age, previous ASCVD, hypertension, increased LDL-CLp(a)-years, and elevated Lp(a) being independently predictive of an event. Conclusion: The need for AVR due to AVS is significantly increased in FH patients, particularly in those who are older and have previous ASCVD, hypertension, increased LDL-CLp(a)-years and elevated Lp(a). Reduction in LDL-C and Lp(a) together with control of hypertension could retard the progression of AVS in FH, but this needs testing in clinical trials. number NCT02693548.

Original languageEnglish
Pages (from-to)2201-2211
Number of pages11
JournalEuropean Heart Journal
Issue number22
Publication statusPublished - 7 Jun 2021


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