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.

Cataract Surgery in Elderly Subjects with Heterozygous Familial Hypercholesterolemia in Prolonged Treatment with Statins

“…Ninety-nine out of the 112 (88.4%) HeFH patients were on high-potency statins (atorvastatin 40-80 mg and rosuvastatin 20-40 mg). We did not observe any differences in smoking, hypertension, and DM between cases and controls [12]. A history of cataract surgery was present in 25.2 % of cases and 16.1% of controls, without difference in gender distribution.…”

“…We studied HeFH cases and controls from five lipid clinics in Spain. The protocol has been previously published [12] and was designed to explore non-coronary morbidities in elder HeFH. In brief, we recruited subjects with age ≥65 years; men and women, with a pathogenic mutation in a candidate gene for FH (LDLR, APOB, or PCSK9) in the subject or in a first-degree relative; LDLc levels ≥220 mg/dL without lipid-lowering therapy; and statin treatment for ≥5 years.…”

Ten things to know about ten cardiovascular disease risk factors

“…Aortic stenosis is also often found in patients with FH, potentially detected by heart murmur upon auscultation of the heart, and whose onset and severity are dependent on lifetime exposure to increased LDL-C levels. [374] Cascade (family) screening for FH is recommended in individuals and families with very high LDL-C levels. [375] High intensity statin (atorvastatin 80 mg or 40 mg per day, or rosuvastatin 40 or 20 mg per day) is first-line treatment for patients with FH.…”

“…Aortic stenosis is also often found in patients with FH, potentially detected by heart murmur upon auscultation of the heart, and whose onset and severity are dependent on lifetime exposure to increased LDL-C levels. [374] …”

Ten things to know about ten cardiovascular disease risk factors (“ASPC Top Ten – 2020”)

“… While tendon xanthomas can rarely be associated with increases in non-cholesterol sterol concentration (i.e., sitosterolemia) [ 192 ], tendon xanthomas are the physical exam finding most pathognomonic for FH, and the physical exam finding most included in FH diagnostic criteria (see Table 10c , Table 10a , Table 10b a – b). Aortic stenosis is also often found in patients with FH, potentially detected by heart murmur upon auscultation of the heart, and whose onset and severity are dependent lifetime exposure to increased cholesterol levels [ 193 ]. Cascade (family) screening for FH is recommended in individuals and families with very high LDL-C levels [ 194 ].…”