Familial Hypercholesterolemia and Pregnancy

Educational Objectives

The goal of this program is to improve the management of reproductive-aged women with familial hypercholesterolemia (FH). After hearing and assimilating this program, the clinician will be better able to:

1. Counsel women with FH during and before pregnancy.

2. Review the impact of FH on the children of women with FH.

Summary

Lipoprotein metabolism during pregnancy: upregulation of hormone-sensitive lipase occurs, which increases circulating free fatty acid (FFA); FFA enters liver and becomes converted to triglycerides (TGs); insulin resistance increases; estradiol increases apolipoprotein A-1, which increases very low density lipoprotein (VLDL) and decreases hepatic lipase, which leads to increased levels of high-density lipoprotein (HDL) cholesterol; decrease in circulatory lipoprotein lipase levels alters peripheral catabolism of TG-rich lipoproteins; as pregnancy progresses, levels of TG, total cholesterol, and low-density lipoprotein cholesterol increase, and they persist for several months postpartum; HDL levels increase minimally

Familial hypercholesterolemia (FH): heterozygous FH has prevalence of ≈1 in 200; homozygous FH prevalence ≈1 in 250,000; women with FH who become pregnant must stop statin therapy and thus begin pregnancy with higher LDL levels and progress through pregnancy with increasingly higher LDL levels compared to women without FH

Recommendations: National Institute for Health and Care Excellence (NICE) guidelines — released in 2009 (United Kingdom); recommend that women stop statins 3 mo before attempting pregnancy; women who become pregnant while on statin therapy should discontinue medication and be referred to obstetrician and lipid specialist; women should not restart statin therapy until pregnancy and lactation completed; as of 2009, only bile acid sequestrants (eg, colesevelam) approved as pregnancy category B agents; National Lipid Association guidelines — released in 2011, and similar to NICE guidelines; recommend prepregnancy counseling for women with FH; statins, ezetimibe, and niacin should not be used during pregnancy; consider LDL apheresis during pregnancy for women with significant atherosclerosis; integrated guidelines — developed by International FH Foundation; similar to other guidelines; focus on counseling before pregnancy; statins contraindicated during pregnancy, especially in first trimester; statins associated with vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities (VACTERL) in exposed fetuses; most data about statins in pregnancy based on studies of hydrophobic statins (eg, lovastatin, simvastatin, atorvastatin); hydrophilic statins (eg, pravastatin, rosuvastatin) released after dangers of statin use in pregnancy clear and thus have little data available about safety in pregnancy

Contraception: low-estrogen oral contraceptives, intrauterine devices, and barrier techniques preferred for women with FH; women who become pregnant while on statins should be referred, but likelihood of fetal complication relatively low

FH risks during pregnancy: relative risk of having cardiovascular (CV) event during third decade of life 125 times greater for women with FH compared to age-matched controls; particularly important for women with FH to receive early treatment, as those planning one or more pregnancies will not be able to receive therapy during significant portion of their lives; registry data indicate 25% of those with FH not on therapy, but only 3% of those because of pregnancy; data indicate cholesterol levels in early pregnancy do not correlate with increased risk for preeclampsia, preterm delivery, fetal loss, or intrauterine growth restriction; registry study found that women with FH do not appear to have higher risk for preterm delivery or having infants with low birth weight or congenital malformation compared to other women

Risks to children from maternal FH: study that looked at pathologic specimens of aorta in children who died of other causes found significant correlation between maternal hypercholesterolemia and abnormal pathology; data show children of hypercholesterolemic mothers have significantly higher LDL levels and macrophage infiltration compared to controls; one study of FH inheritance found total cholesterol and LDL levels higher in children with maternal vs paternal FH inheritance, leading some to suggest fetal origin of adulthood disease; however, mortality rates similar among women with FH regardless of maternal vs paternal inheritance; recent reanalysis of data does not support hypothesis of fetal origin of adulthood disease

Treatment of FH in young women: FH leads to premature atherosclerosis; incidence of CV disease in young women with FH lower compared to young men with FH, but higher than general population; lifestyle adjustments important; statins considered drug of choice, but bile acid sequestrants only safe agents to use in pregnancy (pregnancy category B); other agents (mipomersan and colesevelam) labeled as pregnancy category B but lack adequate well-controlled studies in pregnant women; LDL apheresis can be considered in pregnant women with FH and known atherosclerosis; fibrates, ezetimibe, niacin, and cholestyramine all pregnancy category C; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors — monoclonal antibodies that do not cross blood-placenta barrier during first trimester, but do cross it during second and third trimesters; contraindicated in pregnancy due to lack of data to inform any drug-associated risk

Counseling about drug risk in pregnancy: study found that dermatologists best at documenting contraceptive counseling with prescriptions for class D or X drugs in women of reproductive age; physicians who prescribe statins have lowest rate of such documentation; speaker’s institution has developed waiver to use when prescribing potentially teratogenic drugs

Readings

Suggested Reading

Gidding SS et al: The Agenda for Familial Hypercholesterolemia: a scientific statement from the American Heart Association. Circulation 2015 Dec 1;132(22):2167-92; Goldberg AC et al: Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 2011 Jun;5(3 Suppl):S46-51; Eapen DJ: Management of familial hypercholesterolemia during pregnancy: case series and discussion. J Clin Lipidol 2012 Jan-Feb;6(1)88-91; Kusters DM et al: Dilemmas in treatment of women with familial hypercholesterolemia during pregnancy. Neth J Med 2010 Aug;68(1):299-303; Napoli C et al: Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study. Lancet 1999 Oct 9;354(9186):1234-41; Vrijkotte TG et al: Maternal lipid profile during early pregnancy and complications and outcomes: the ABCD study. J Clin Endocrinol Metab 2012 Nov;97(11):3917-25; Watts GF et al: Integrated guidance on the care of familial hypercholesterolemia from the International FH Foundation. J Clin Lipidol 2014 Mar-Apr;8(2):148-72.

Disclosures

For this program, the following has been disclosed: Dr. Underberg is a consultant for Aegerion, Amarin, Amgen, AstraZeneca, Eli Lilly and Company, Recombine, Regeneron Pharmaceuticals, and sanofi-aventis US; receives grant/research support from Aegerion and Pfizer; and is on Speakers’ Bureaus for Aegerion, Amgen, AstraZeneca, Genzyme (subsidiary of sanofi-aventis), Merck & Co, Regeneron, and sanofi-aventis US. The planning committee reported nothing to disclose.

Acknowledgements

Dr. Underberg was recorded at Cardiovascular Disease Prevention: Baptist Health South Florida’s 14th Annual International Symposium and Miami Cardiac and Vascular Institute Cardiovascular Summit, held February 18-21, 2016, in Miami, FL, and presented by Baptist Health South Florida. For information about upcoming CME activities presented by Baptist Health South Florida, please visit: baptisthealth.net/en/physicians/pages/continuing-medication-education.aspx. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

FP644102

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.