Lp(a), LDL-C, Hypertension: Predictors of Need for AVR in FH

Jan 20, 2021
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Authors:
Peréz de Isla L, Watts GF, Alonso R, et al.
Citation:
Lipoprotein(a), LDL-Cholesterol, and Hypertension: Predictors of the Need for Aortic Valve Replacement in Familial Hypercholesterolemia. Eur Heart J 2021;Jan 12:[Epub ahead of print].
Summary By:
Melvyn Rubenfire, MD, FACC

Quick Takes

  • Aortic valve stenosis (AVS) is in the spectrum of ASCVD with LDL-C as a risk factor, particularly in heterozygous familial hypercholesterolemia (HeFH), yet statins have not been shown to reduce the progression of AVS.
  • Amongst the reasons may be the need to treat hypertension and LDL-C earlier in the course of aortic valve calcification and stenosis, particularly in persons with HeFH, polygenic hypercholesterolemia, and LDL-C >160 mg/dl considering that the risk attributable to LDL-C is related to years of exposure.
  • The risk of AVS attributable to LDL-C-years seems to be related to LDL-CLp(a)-years or the impact of associated familial elevation of Lp(a), which is present in very young children and is not reduced with statins or other available therapies.

Study Questions:

What is the frequency of severe aortic valve stenosis (AVS) and are there predictors of need for aortic valve replacement (AVR) in molecularly defined patients with familial hypercholesterolemia (FH) and elevated lipoprotein (a) [Lp(a)]?

Methods:

SAFEHEART is a long-term (15-year) prospective cohort study of a population with FH and nonaffected relatives (NARs). The authors analyzed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3,712 with FH; 1,310 with NARs).

Results:

Fifty patients with FH (1.48%) and three NARs (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 atherosclerotic cardiovascular disease (ASCVD), hypertension, increased low-density lipoprotein cholesterol (LDL-C)Lp(a)-years, and elevated Lp(a) being independently predictive of an event.

Conclusions:

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.

Perspective:

The finding in this unique large observational study supports the epidemiology studies of risk factors for severe AVS and provides the hypothesis that early targeted treatment of hypertension, LDL-C, and Lp(a) (when treatment is available) may reduce incident AVS and need for AVR.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and VHD, Advanced Lipid Testing, Lipid Metabolism, Nonstatins, Primary Hyperlipidemia, Interventions and Structural Heart Disease, Hypertension

Keywords: Antihypertensive Agents, Aortic Valve Stenosis, Atherosclerosis, Cholesterol, LDL, Heart Valve Diseases, Heart Valve Prosthesis, Hyperlipoproteinemia Type II, Hypertension, Lipoprotein(a), Metabolic Syndrome, Primary Prevention, Risk Factors, Transcatheter Aortic Valve Replacement


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