Survival in homozygous familial hypercholesterolaemia is determined by the on-treatment level of serum cholesterol.

Aims: Homozygous familial hypercholesterolaemia (FH) is a rare inherited disorder characterized by extreme hypercholesterolaemia from birth, accelerated atherosclerosis, and premature death. Many forms of lipid-lowering therapies have been used in the past, but definitive evidence of benefit has been lacking. We therefore undertook a retrospective survey of lipid levels and clinical outcomes of FH homozygotes treated with a combination of lipid-lowering measures between 1990 and 2014 in South Africa and the UK. Methods and results: We divided 133 previously statin-naive homozygotes into quartiles according to their on-treatment levels of serum cholesterol and compared the occurrence of any death, cardiovascular death, and major adverse cardiovascular events (MACE) between the quartiles during 25 years of follow-up, using Cox and competing risks regression analysis. Patients in Quartile 4, with an on-treatment serum cholesterol >15.1 mmol/L, had a hazard ratio of 11.5 for any death compared with those in Quartile 1, with an on-treatment cholesterol of < 8.1 mmol/L. Those in Quartiles 2 and 3 combined, with on-treatment cholesterol of 8.1-15.1 mmol/L had a hazard ratio of 3.6 compared with Quartile 1. These differences were statistically significant (P < 0.001) and remained so after adjustments for confounding factors (P = 0.04). Significant differences between quartiles were also evident for cardiovascular deaths and MACE. Conclusion: These findings provide unequivocal evidence that the extent of reduction of serum cholesterol achieved by a combination of therapeutic measures, including statins, ezetimibe, lipoprotein apheresis, and evolocumab, is a major determinant of survival in homozygous FH.

Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy.

BACKGROUND: Homozygous familial hypercholesterolemia is an inherited disorder caused by mutations in both low-density lipoprotein receptor alleles, which results in extremely elevated plasma low-density lipoprotein cholesterol concentrations and very early morbidity and mortality due to cardiovascular disease. METHODS AND RESULTS: To evaluate the impact of advances in lipid-lowering (predominantly statin) therapy on cardiovascular disease morbidity and mortality in a large cohort of patients with homozygous familial hypercholesterolemia, the records of 149 patients (81 females, 68 males) from 2 specialized lipid clinics in South Africa were evaluated retrospectively. Homozygous familial hypercholesterolemia was diagnosed by confirmation of mutations in genes affecting low-density lipoprotein cholesterol or by clinical criteria. A Cox proportional hazard model with time-varying exposure was used to estimate the risk of death and major adverse cardiovascular events among statin-treated patients compared with statin-naive patients. The hazard ratio for benefit from lipid therapy, calculated with the Cox proportional hazards model for the end point of death, was 0.34 (95% confidence interval 0.14-0.86; P=0.02), and for the end point of major adverse cardiovascular events, it was 0.49 (95% confidence interval 0.22-1.07; P=0.07). This occurred despite a mean reduction in low-density lipoprotein cholesterol of only 26.4% (from 15.9±3.9 to 11.7±3.4 mmol/L; P<0.0001) with lipid-lowering therapy. CONCLUSIONS: Lipid-lowering therapy is associated with delayed cardiovascular events and prolonged survival in patients with homozygous familial hypercholesterolemia.

Statins and other lipid-lowering therapy and pregnancy outcomes in homozygous familial hypercholesterolaemia: A retrospective review of 39 pregnancies.

BACKGROUND AND AIMS: Pregnancy in HoFH females is associated with further elevation of already markedly elevated low density lipoprotein cholesterol (LDL-C) levels, particularly if lipid-lowering therapy is discontinued, placing the mother and fetus at increased cardiovascular risk. Lipoprotein apheresis is the current recommended treatment for pregnant HoFH patients. However, this is costly, time consuming, and is not available in many countries. Alternative treatment strategies to control hypercholesterolaemia during pregnancy in HoFH patients are necessary. METHODS: This study was a retrospective review of 39 pregnancies from a cohort of 20 genotypically confirmed female HoFH patients. RESULTS: No maternal cardiac complications or deaths occurred during the pregnancies or during the first year postpartum. Twenty five pregnancies were exposed to lipid-lowering therapy, of which 18 were exposed to statin therapy, just prior to or during the pregnancy. Thirty three (84%) pregnancies carried to term, 3 (8%) premature deliveries and 3 (8%) miscarriages were observed. Complications associated with pregnancy in these HoFH patients, did not differ from those reported during pregnancies of otherwise healthy woman. CONCLUSIONS: HoFH is a severe disease impacting significantly on life expectancy. However, for many females with HoFH, despite the high cardiovascular risk, pregnancy is not uncommon. In resource poor settings and when LA is not available, lipid lowering therapy, particularly statin therapy during pregnancy, appears to be safe for both mother and fetus and is an acceptable alternative for LDL-C reduction in these high risk patients.