Brigitte C. Brice

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.

Healthy multiparous women having elective interval (N = 69) or postpartum (N = 69) sterilization were interviewed pre-operatively and 6 weeks and 6 months post-operatively, using standardized instruments. They did not differ significantly from control samples of comparable non-sterilized women with respect to mental state (Present State Examination) or subjectively-assessed mental or physical health or abdominal pain. More sterilization subjects than control subjects reported subjectively experienced improvement in sexual satisfaction at the later follow-up. Reports of poor physical health and abdominal pain increased over time within both the sterilization and the control groups. Reports of adverse effects at follow-up were often associated with higher PSE scores initially. Regrets and wish for reversal were rare and were also associated with higher initial PSE scores. Since the adverse effects were more common among postpartum subjects, it is suggested that subjectively experienced sequelae of sterilization may sometimes be attributable to 'normal' postnatal events.