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Panagiotis Anagnostis, Dimitrios G Goulis, Letter to the Editor: “Familial Hypercholesterolemia and Risk of Peripheral Arterial Disease and Chronic Kidney Disease”, The Journal of Clinical Endocrinology & Metabolism, Volume 104, Issue 8, August 2019, Page 3124, https://doi.org/10.1210/jc.2019-00413
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We read with interest the study by Emanuelsson et al. (1) showing an association between familial hypercholesterolemia (FH) and risk of peripheral artery disease (PAD).
Some comments might be of interest. Most studies, in both children and adults with FH, have shown higher lipoprotein (a) [Lp(a)] concentrations compared with non-FH subjects. About 30% of patients with FH have Lp(a) concentrations >50 mg/dL, which has been recognized as the threshold above which the risk of cardiovascular disease (CVD) increases significantly. Moreover, the association between Lp(a) and CVD seems to be stronger in patients with FH and a history of CVD than in those without (2). Even patients with FH and lower Lp(a) concentrations (>30 mg/dL) are at 1.5-fold higher risk of CVD, including PAD, as shown by large cohort studies (3).
In general, PAD has been scarcely studied in patients with FH, because the lion’s share of increased CVD risk has focused on coronary artery disease (CAD). Notwithstanding its well-documented independent association with CAD, Lp(a) seems also to be independently associated with the risk of PAD in patients with FH, even to a lesser extent than CAD (4, 5). Some studies, such as those in patients with type 2 diabetes mellitus, have suggested a 2.7-fold increased risk of PAD for patients with Lp(a) >13.3 mg/dL (5). In the study by Emanuelsson et al. (1), although Lp(a) concentrations were higher in those with possible or probable/definite FH compared with non-FH, they did not modify the association between FH and PAD risk. An explanation could be that only a few patients with FH had Lp(a) >30 mg/dL, which could have further augmented PAD risk. Therefore, a separate analysis on this concept would be of value. We think Lp(a) concentrations should be assessed in patients with FH to identify those at higher risk of PAD, who could benefit more from pharmaceutical intervention.
Acknowledgments
Disclosure Summary: The authors have nothing to disclose.
