Lipoprotein(a) as Risk Factor in Heterozygous Familial Hypercholesterolemia
Lipoprotein(a) cholesterol is a risk factor for aortic valve calcification and a significant predictor of clinical aortic stenosis in patients with heterozygous familial hypercholesterolemia.
The combination of an elevated lipoprotein(a) cholesterol (Lp[a]) and an elevated low-density lipoprotein cholesterol level in patients with heterozygous familial hypercholesterolemia (he-FH) increases atherosclerotic cardiovascular disease (ASCVD) risk and potentially increases the risk for aortic valve calcification (AVC), according to review results published in Atherosclerosis.
In this review, the researchers discussed the current knowledge regarding Lp(a) as a risk factor for AVC and as an important precursor of clinical aortic stenosis (AS) in patients with he-FH and also noted new treatment options for lowering Lp(a) levels.
Previous studies have shown significant associations between Lp(a) levels >30-50 mg/dL and calcific aortic valve stenosis, and adult patients with he-FH have a >2-fold higher prevalence of AVC compared with healthy control participants. Lipoprotein(a) cholesterol levels >50 mg/dL were also recently identified as an independent risk factor for AVC in patients with asymptomatic he-FH who took statins.
With a worldwide estimate of 1.4 billion people with Lp(a) levels >50 mg/dL and 1 in 250 people with he-FH, then approximately 5 million patients with he-FH should have Lp(a) levels >50 mg/dL. Furthermore, as patients with he-FH have significantly higher Lp(a) levels, on average, the actual number should be even higher. The review researchers, who recently proposed Lp(a) life-years (the age-dependent exposure to a given Lp(a) level (years × mg/dL)] as a useful metric of cumulative burden of risk for ASCVD, now proposed this metric can extend to AVC risk.
Novel pharmacotherapies that use small interfering RNA (siRNA)-based therapies or apo(a) antisense oligonucleotides have been shown to be effective at targeting the hepatic expression of apo(a) and offer the potential for significant reductions in the aortic valve's cumulative Lp(a) exposure.
Study investigators concluded, "These new apo(a) antisense oligonucleotides, and also the specific siRNAs under development, all need to be tested in controlled clinical intervention trials to learn about their effects on the progression of ASCVD."
Vuorio A, Watts GF, Kovanen PT. Lipoprotein(a) as a risk factor for calcific aortic valvulopathy in heterozygous familial hypercholesterolemia. Atherosclerosis. 2018;281:25-30.