Familial hypercholesterolaemia in pregnancy: Australian case series and review.

BACKGROUND: Familial hypercholesterolaemia (FH) is associated with a significant increase in the risk of premature coronary artery disease. Pregnancy is likely a vulnerable time for atherosclerosis progression, with a physiological rise in low-density lipoprotein cholesterol (LDL-C) further exaggerated by the discontinuation of cholesterol-lowering therapy. MATERIALS AND METHODS: A retrospective review was undertaken of 13 women with familial hypercholesterolemia who were managed during pregnancy between 2007 and 2021 by a multidisciplinary team following individualised risk assessment. RESULTS: Overall, pregnancy outcomes were good, with no maternal or fetal complications, including congenital abnormalities, maternal cardiac events or hypertensive complications. Loss of statin treatment time ranged between 12 months and 3.5 years resulting from the accumulation of the preconception, pregnancy and lactation periods and was magnified in women having more than one pregnancy. Of seven women treated with cholestyramine, one developed abnormal liver function with an elevated international normalisation ratio which was corrected with vitamin K. CONCLUSION: Pregnancy is associated with prolonged cessation of cholesterol-lowering therapy, a concern with respect to the risk of coronary artery disease in FH. Continuation of statin therapy up to conception and even during pregnancy in patients at higher risk of cardiovascular disease may be justified, especially with increasing evidence supporting the safety of statin therapy during pregnancy. However, more long-term maternal and fetal data are required for the routine use of statins during pregnancy. Guideline-informed models of care covering family planning and pregnancy should be implemented for all women with FH.

Cascade testing for elevated lipoprotein(a) in relatives of probands with high lipoprotein(a).

Objective: Elevated lipoprotein(a) [Lp(a)] is a common inherited condition associated with cardiovascular disease. This study investigated whether cascade testing for Lp(a) was effective in detecting new cases of elevated Lp(a) in families. Methods: Relatives from adult probands with Lp(a) concentration ≥100 mg/dL were tested for elevated Lp(a) (≥50 mg/dL) via a cascade testing program in a tertiary hospital setting. The prevalence and yield of detecting new cases of elevated Lp(a) among the relatives were assessed. Results: Of the 83 probands, 43.4% had familial combined hyperlipidemia (FCHL) and 34.9% common hypercholesterolemia (CH). Among 182 relatives tested (151 adults and 31 children), elevated Lp(a) was found in 68.1%, with 32.9% having Lp(a) between 50 and 99 mg/dL and 35.2% having Lp(a) ≥100 mg/dL. One new case of elevated Lp(a) ≥50 mg/dL was identified for every 1.5 relatives tested and 1 new case of elevated Lp(a) ≥100 mg/dL for every 2.8 relatives tested. The proportion of relatives detected with elevated Lp(a) was significantly higher when tested from probands with Lp(a) >150 mg/dL compared with those with Lp(a) between 100 and 150 mg/dL (81.1% vs. 55.5%; P = 0.001). The concordance rates (kappa coefficient) for the detection of elevated Lp(a) with FCHL and CH were 34.8% (0.026) and 53.2% (0.099), respectively. Conclusion: Cascade testing for elevated Lp(a) from affected probands with phenotypic dyslipidemia is highly effective in identifying new cases of high Lp(a) in families. The yield of detecting elevated Lp(a) is greater when probands have higher levels of Lp(a) and exceeds the detection of relatives with FCHL and CH.

Effectiveness of proprotein convertase subtilisin/kexin-9 monoclonal antibody treatment on plasma lipoprotein(a) concentrations in patients with elevated lipoprotein(a) attending a clinic.

BACKGROUND: Lipoprotein(a) (Lp[a]) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin-9 monoclonal antibodies (PCSK9mAbs) can lower Lp(a) levels in clinical trials, but their effects in patients with elevated Lp(a) in clinical practice remain unclear. AIMS: To investigate the effectiveness and safety of PCSK9mAbs in lowering plasma Lp(a) in patients with elevated Lp(a) concentrations in a lipid clinic. METHODS: This was an open-label study of 53 adult patients with elevated Lp(a) concentration (≥0.5 g/L). Clinical, biochemical, and safety data were collected before and on treatment with evolocumab or alirocumab over a mean period of 11 months. RESULTS: Treatment with a PCSK9mAb resulted in a significant reduction of 0.29 g/L (-22%) in plasma Lp(a) concentration (p<.001). There were also significant reductions in low-density lipoprotein-cholesterol (LDL-C) (-53%), remnant-cholesterol (-12%) and apolipoprotein B (-43%) concentrations. The change in Lp(a) concentration was significantly different from a comparable group of 35 patients with elevated Lp(a) who were not treated with a PCSK9mAb (-22% vs. -2%, p<.001). The reduction in Lp(a) concentration was not associated with the corresponding changes in LDL-C, remnant-cholesterol, and apolipoprotein B (p>.05 in all). 7.5% and 47% of the patients attained a target concentration of Lp(a) <0.5 g/L and LDL-C <1.8 mmol/L, respectively. PCSK9mAbs were well tolerated, the common adverse effects being pharyngitis (9.4%), nasal congestion (7.6%), myalgia (9.4%), diarrhoea (7.6%), arthralgia (9.4%) and injection site reactions (11%). CONCLUSION: PCSK9mAbs can effectively and safely lower plasma Lp(a) concentrations in patients with elevated Lp(a) in clinical practice; the impact of the fall in Lp(a) on ASCVD outcomes requires further investigation.