Maternal inheritance of FH may increase odds of subclinical coronary calcium by midlife
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Researchers in France observed that maternal inheritance of familial hypercholesterolemia was associated with greater odds of having subclinical coronary atherosclerosis compared with paternal inheritance of the gene mutation.
However, there was significant difference in the occurrence of atherosclerotic CVD events among patients with maternal compared with paternal inheritance of familial hypercholesterolemia (FH), according to data published in Arteriosclerosis, Thrombosis, and Vascular Biology.
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“In this study, we showed for the first time that maternal inheritance of FH gene mutation was associated with a higher coronary artery calcium score, raised by 94 Agatston units (95% CI, 22-166; P = .01), a 1.81-fold risk of having a CAC score greater than 100 Agatston units and a 2.72-fold risk of having a CAC score > 400 Agatston units when compared with paternal inheritance,” Florian Mourre, MD, of the department of nutrition, metabolic diseases and endocrinology at La Conception Hospital and the Aix Marseille University in Marseille, France, and colleagues wrote. “These findings suggest that patients with maternal inheritance for heterozygous FH had greater subclinical coronary atherosclerosis as assessed by CAC score than those with paternal inheritance of the disease.”
Using data from the French Registry of Familial Hypercholesterolemia (REFERCHOL), Mourre and colleagues retrospectively included 1,350 participants (51% women) with a documented genetic FH diagnosis to evaluate whether maternal or paternal inheritance of FH was associated with subclinical ASCVD. Patients free of coronary CV events at baseline with a subclinical ASCVD evaluation assessed using CAC score were propensity-matched by inheritance of the FH gene mutation, maternal compared with paternal.
Maternal vs. paternal inheritance of FH
Patients with a maternal inheritance of FH were on average 2 years older compared with those with paternal inheritance (46.9 vs. 44.7 years; P = .02), had a lower prevalence of PCSK9 mutations (2% vs. 4.1%; P = .03) and were less likely to have a family history of premature CVD (27.7% vs. 45%; P < .0001).
Researchers observed no difference in prevalence of other CV risk factors between the two FH groups and no differences in the prevalence of ASCVD events (maternal, 21%; paternal, 20%; P = .91), number of events per patient (1.7 in both groups; P = .43), age at first event, number of recurrences or time to recurrence of CV events in either group.
Maternal inheritance of the FH gene mutation was associated with an 86% higher CAC score compared with paternal inheritance (95% CI, 23-170; P = .003), according to the study.
Moreover, maternal inheritance was associated with a nearly twofold greater odds for having a CAC score of 100 or more (HR = 1.81; 95% CI, 1.06-3.11; P = .03) and a nearly threefold greater odds for having a CAC score of 400 or more (HR = 2.72; 95% CI, 1.39-5.51; P = .004) compared with paternal inheritance of the FH gene mutation.
“Despite CAC score [being] a good predictor of ASCVD, maternal inheritance had no observed effect on the occurrence of ASCVD events in the present study,” the researchers wrote. “This discrepancy, between subclinical coronary atherosclerosis and the occurrence of ASCVD events, may be due to the relatively young age of the patients, with an average age of 45.7 years old for the total population, and the increased ASCVD risk in women after the menopause.”
Other factors associated with CAC score
In addition, other factors associated with an elevated CAC score were male sex (230% increase vs. female sex; 95% CI, 129-447; P < .001), family history of premature ASCVD (99% increase vs. no family history; 95% CI, 30-200; P = .002), high BP (136% increase vs. normal BP; 95% CI, 25-348; P = .009), elevated LDL (0.44% increase per every 1 mg/dL; 95% CI, 0-1; P = .002) and age at CAC measurement (11% increase for every 1 year; 95% CI, 8-12; P = .001).
“Our results suggest that exposure to high levels of cholesterol during pregnancy should be considered as a supplemental cardiovascular risk factor,” the researchers wrote. “If our results are confirmed by other studies, it would then be of importance to more intensively treat FH adults when the genetic mutation is maternally inherited, to limit the progression of ASCVD.”
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