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Aortic Valvular Disease in Elderly Subjects with Heterozygous Familial Hypercholesterolemia: Impact of Lipid-Lowering Therapy.

ABSTRACT: Hypercholesterolemia and statins are risk factors for aortic stenosis (AS) and vascular calcification, respectively. Whether heterozygous subjects with familial hypercholesterolemia (HeFH) treated with statins are at risk of AS is unknown. We study the prevalence of AS, aortic valve calcification (AoVC), and aortic sclerosis (ASc) in elderly subjects with HeFH in a prolonged statin treatment. Case-control study, cases were adults ?65 years of age with a genetic diagnosis of HeFH, LDLc >220 mg/dl, and statin treatment ?5 years. Controls were relatives of HeFH patients, with LDLc <190 mg/dl. Participants underwent a cardiac ultrasound for aortic valve analysis. We studied 205 subjects, 112 HeFH and 93 controls, with mean age 71.8(6.5) years and 70.0(7.3) years, respectively. HeHF, with respect to controls, presented greater gradients of aortic transvalvular pressure, 7.4(7.3) mmHg versus 5.0(2.8) mmHg, and maximum aortic velocity, 1.7(0.7) m/s versus 1.5(0.4) m/s, and lower aortic valve opening area, 2.0(0.7) cm² versus 2.4(0.6) cm² (all p < 0.05). AoVC and ASc were also more prevalent in HeFH (p < 0.05 between groups). Moderate/severe AS prevalence was higher among HeFH: 7.1% versus 1.1% (age- and sex-adjusted odds ratio (OR) 8.33, p = 0.03). Independent risk factors for aortic valve disease in HeFH were age and LDLc before treatment. The number of years under statin treatment was not associated with any aortic valve measurement. Subjects ?65 years with HeFH in prolonged statin treatment show more aortic valvular disease and higher frequency of AS than controls. Life-long elevated LDLc exposure, rather than time of exposure to statins, explains this higher risk.

SUBMITTER: Marco-Benedi V

PROVIDER: S-EPMC6947617 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Aortic Valvular Disease in Elderly Subjects with Heterozygous Familial Hypercholesterolemia: Impact of Lipid-Lowering Therapy.

Marco-Benedí Victoria V Laclaustra Martin M Casado-Dominguez Juan M JM Villa-Pobo Rosa R Mateo-Gallego Rocío R Sánchez-Hernández Rosa M RM Blanco Nuez Marta M Ortega-Martínez de Victoria Emilio E Sitges Marta M Pedro-Botet Juan J Puzo Jose J Villarroel Teresa T Civeira Fernando F

Journal of clinical medicine 20191214 12

Hypercholesterolemia and statins are risk factors for aortic stenosis (AS) and vascular calcification, respectively. Whether heterozygous subjects with familial hypercholesterolemia (HeFH) treated with statins are at risk of AS is unknown. We study the prevalence of AS, aortic valve calcification (AoVC), and aortic sclerosis (ASc) in elderly subjects with HeFH in a prolonged statin treatment. Case-control study, cases were adults ≥65 years of age with a genetic diagnosis of HeFH, LDLc >220 mg/dl ...[more]

PMID: 31847331

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Project description:BackgroundAlthough statins (STs) are drugs of first choice in hypercholesterolemic patients, especially in those at high cardiovascular risk, some of them are intolerant to STs or refuse treatment with these drugs. In view of this, we have evaluated the lipid-lowering effect of a nutraceutical pill containing berberine (BBR) and of ezetimibe, as alternative treatments, in monotherapy or in combination, in 228 subjects with primary hypercholesterolemia (HCH), with history of STs intolerance or refusing STs treatment. In addition, since PCSK9 was found up-regulated by STs dampening their effect through an LDL receptors (LDLRs) degradation, and BBR suppressed PCSK9 expression in cellular studies, we supplemented the stable lipid-lowering therapy of 30 genotype-confirmed Familial Hypercholesterolemia heterozygotes (HeFH) with BBR, searching for a further plasma cholesterol reduction. Plasma lipid pattern was evaluated at baseline and during treatments.ResultsIn HCH subjects the nutraceutical pill resulted more effective than EZE in lowering LDL cholesterol (-31.7% vs -25.4%, P < 0.001) and better tolerated. On treatment, LDL-C level below 3.36 mmol/L (≤130 mg/dl) was observed in 28.9% of subjects treated with the nutraceutical pill and 11.8% of those treated with EZE (P <0.007). In the group treated with EZE the subjects carrying the G allele of the g.1679 C > G silent polymorphism of NPC1L1 gene showed a higher response to EZE than homozygous for the common allele (GG + CG: LDL-C -29.4±5.0%, CC -23.6±6.5%, P <0.001). Combined treatment with these drugs was as effective as STs in moderate doses (LDL cholesterol -37%, triglycerides -23%). In HeFH patients the addition of BBR resulted in LDL cholesterol reductions inversely related to those induced by the stable therapy (r = -0.617, P <0.0001), with mean 10.5% further decrease.ConclusionsThe alternative treatments tested in our HCH subjects were rather effective and safe. The findings in HeFH patients suggest that BBR might act in vivo increasing expression and stability of LDLRs and/or suppressing PCSK9 expression.

Dataset Information

Aortic Valvular Disease in Elderly Subjects with Heterozygous Familial Hypercholesterolemia: Impact of Lipid-Lowering Therapy.

Publications

Aortic Valvular Disease in Elderly Subjects with Heterozygous Familial Hypercholesterolemia: Impact of Lipid-Lowering Therapy.

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