A 26–year-old woman has an LDL–C of 260 mg/dL, HDL–C of 51 mg/dL, and triglycerides of 102 mg/dL. She reports having elevated LDL–C levels of over 200 mg/dL since her teens and has tried various diets without success but has never taken a drug to lower her cholesterol. She is worried because her father died suddenly at age 38 and her father's brother had a myocardial infarction at age 32. Both were smokers. She is currently on a 2nd generation oral contraceptive and wonders if she should get off the contraceptive pill since she is engaged to be married in 6 months. She has an occasional cigarette and says that it is "social smoking." On exam, BP is 110/60 mm Hg and BMI is 24. She has bilateral inferior pole corneal arcus, no xanthelasma, and thickened Achilles tendons. Her cardiovascular examination is normal.
Which of the following is the best answer?
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The correct answer is: a. She likely has heterozygous familial hypercholesterolemia and should start a high-intensity statin.
She has heterozygous familial hypercholesterolemia (FH), which places her in a statin benefit group. Adults with LDL–C ≥190 mg/dL are likely to have a genetic cholesterol disorder since childhood, placing them at high risk of ASCVD. Therefore, statin therapy should be started by age 21 years, if not started before then. Although no RCTs were performed exclusively in FH populations, many randomized trials enrolled individuals with LDL–C levels ≥190 mg/dL. The 2010 CTT meta-analysis found that statins reduce ASCVD events across the range of LDL–C levels >70 mg/dL and also showed that the magnitude of ASCVD risk reduction is proportional to the degree of LDL–C lowering. Therefore, individuals with FH should receive a high–intensity statin. Addition of non-statin therapy to further lower LDL–C may be considered in some FH patients.
This patient should continue effective contraception during statin therapy. She should avoid getting pregnant or nursing on the statin due to classification of statins (and most nonstatin drugs) as pregnancy category X. Once she definitely plans to become pregnant, she should stop the statin 2-3 months before discontinuing her oral contraceptive. Once child-bearing and nursing is complete, the effective contraception and the statin should be resumed.
Because she has a long-standing history of markedly elevated total cholesterol and LDL–C levels there is no need to rule out secondary causes of hypercholesterolemia prior to initiating therapy. If this was the initial evaluation of a patient with LDL–C ≥190 mg/dL, secondary causes of hypercholesterolemia should be ruled out (hypothyroidism, obstructive biliary disease, nephrotic syndrome are common causes).
The degree of LDL–C elevation at her age, normal weight, HDL–C of 51 mg/dL and the presence of stigmata of FH (arcus, Achilles tendon xanthomas) make heterozygous FH the most likely diagnosis and a familial form of combined hyperlipidemia unlikely. The early MIs in her father and his brother also make autosomal dominant FH highly likely. Therefore, the risk of her children having her condition is 1 in 2, not 1 in 4 as with each pregnancy there is a 50:50 chance of her passing on her mutant allele. Once an individual is identified with LDL–C ≥190 mg/dL, family members should also be screened with a fasting or nonfasting lipid panel to identify other affected individuals for early statin therapy.
Individuals with FH should never smoke. In an older series of untreated FH patients, cigarette smoking strikingly increased rates of cardiac events in younger women a well as in younger men. Smoking also explains the early manifestation of myocardial infarction in her father and her paternal uncle. Control of other ASCVD risk factor is also important to further reduce ASCVD risk.
Adults with primary LDL–C ≥190 mg/dL are already identified in a statin benefit group, for whom statin therapy is indicated by age 21 years. Therefore there is never a need to estimate 10-year ASCVD risk in these individuals.
References
Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Scriver Cr, Beaudet AL, Sly WS, Valle D, editors. The Metabolic and molecular basis of inherited disease. New York: McGraw Hill, 2001. p. 2863–2913.
Goldberg AC, Hopkins PN et al. Executive Summary 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; 5, S1–S8.
Stone NJ, Levy, RI, Fredrickson, DS, Verter, J. Coronary artery disease in 116 kindred with familial type II hyperlipoproteinemia. Circ1974; 49: 476-488.
Robinson JG, Goldberg AC. Treatment of adults with Familial Hypercholesterolemia and evidence for treatment: Recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011; 5(3, Supplement 1):S18-S29.
Cholesterol Treatment Trialists Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010; 376:1670-1681.
Ito MK, McGowan MP, Moriarty PM. Management of Familial Hypercholesterolemias in adult patients: Recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011; 5(3, Supplement 1):S38-S45.
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