A case of familial hypercholesterolemia with premature coronary artery disease

Jaywant M Nawale; Ajay S Chaurasia; Digvijay Deeliprao Nalawade; Dhirendra Tiwari

doi:10.4103/heartindia.heartindia_27_18

CASE REPORT

Year : 2018 | Volume : 6 | Issue : 4 | Page : 156-159

A case of familial hypercholesterolemia with premature coronary artery disease

Jaywant M Nawale, Ajay S Chaurasia, Digvijay Deeliprao Nalawade, Dhirendra Tiwari
Department of Cardiology, TNMC and BYL Nair Ch. Hospital, Mumbai, Maharashtra, India

Date of Web Publication

17-Dec-2018

Correspondence Address:
Dr. Digvijay Deeliprao Nalawade
18-ICCU, Department of Cardiology, Ground Floor, OPD Building, Nair Hospital, Mumbai Central, Mumbai - 400 008, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/heartindia.heartindia_27_18

Abstract

Familial hypercholesterolemia (FH) is a form of genetic dyslipidemia characterized by high levels of serum low-density lipoprotein cholesterol, tendon xanthomas, and family history of heart disease or elevated cholesterol. We report the case of a 24-year-old young male who presented with acute coronary syndrome, multiple skin and tendon xanthomas, family history of premature cardiac death and diagnosed as FH with coronary artery disease which was treated with percutaneous coronary intervention and lipid-lowering therapy.

Keywords: Acute coronary syndrome, familial hypercholesterolemia, low-density lipoprotein cholesterol, xanthomas

How to cite this article:
Nawale JM, Chaurasia AS, Nalawade DD, Tiwari D. A case of familial hypercholesterolemia with premature coronary artery disease. Heart India 2018;6:156-9

How to cite this URL:
Nawale JM, Chaurasia AS, Nalawade DD, Tiwari D. A case of familial hypercholesterolemia with premature coronary artery disease. Heart India [serial online] 2018 [cited 2023 May 28];6:156-9. Available from: https://www.heartindia.net/text.asp?2018/6/4/156/247571

Introduction

Familial hypercholesterolemia (FH) is a form of genetic dyslipidemia (type IIa Fredrickson classification) with autosomal dominant inheritance.^[1] It is characterized by elevated levels of serum total and low-density lipoprotein cholesterol (LDL-C). Genetically, the mutations involve genes that encode the LDL receptor, apolipoprotein B/E, etc.^[2] Phenotypically, FH manifests in two forms: heterozygous milder form with a prevalence of 1 in 500 individuals, clinically manifesting in early adulthood and homozygous severe form with a prevalence of 1 in a million individuals, clinically manifesting as early as the first decade.^[1] Cholesterol deposits occurring in FH not only involve peripheral tissues such as skin, tendon and cornea, but can also involve cardiovascular system.

Case Report

A 25-year-old male, born of nonconsanguineous marriage, presented with retrosternal angina of 30-min duration with no history of hypertension, diabetes, addiction or coronary artery disease. Family history revealed premature cardiac death of the elder sister at 11 years of age. General examination of the patient revealed multiple firm, painless, nodular-to-large-sized skin lesions over the elbows, hands, buttocks and knees along with corneal arcus [Figure 1]. Pulse was 120/min with blood pressure of 124/80 mmHg. Cardiovascular and respiratory system examinations were normal. Electrocardiogram showed sinus tachycardia with no significant ST-T changes. Qualitative troponin T was positive. Two-dimensional echocardiography showed normal left ventricular systolic function. He was diagnosed as non-ST-segment elevation myocardial infarction and was initially stabilized with medications. Further history revealed that the skin lesions were initially noted when he was 5 years of age, but no medical care was sought until the skin lesion on his lower back increased to the extent that it required excision for cosmetic reasons at the age of 15 years, details of which were not available.

Figure 1: Cholesterol deposits at various sites in a case of familial hypercholesterolemia. (a) Tendon xanthomas (marked by arrows) and skin xanthomas over the extensor aspect of hands. (b) Large skin xanthomas over the buttocks. (c) Corneal arcus. (d) Skin xanthomas over the extensor aspect of elbow. (e) Skin xanthomas over the flexor aspect of elbow. (f) Skin xanthomas over the extensor aspect of knee

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His total cholesterol was 394 mg/dL with LDL-C of 310 mg/dL, high-density lipoprotein cholesterol of 30 mg/dL, and triglyceride of 86 mg/dL [Table 1]. Family screening revealed elevated total cholesterol in both parents and his younger sister [Table 1] without skin manifestations. Later, his coronary angiogram revealed severe 90% ostial stenosis with proximal long-segment lesion (70%–80%) in the right coronary artery (RCA), which was dominant [Figure 2]; left anterior descending artery (LAD) and left circumflex artery (LCX) (nondominant), showed minor plaques. There was ramus, small caliber with ostial total occlusion, filling retrogradely from the left system. He was treated with early percutaneous coronary intervention (PCI) using two overlapping 3.5 mm × 28 mm drug-eluting stents (XIENCE V, Abbott Vascular) in the RCA [Figure 2]. The decision was to conservatively manage the ramus lesion as it was small in caliber and had narrow angle with the LAD and LCX. He was started on dual antiplatelet therapy, beta-blocker, angiotensin-converting enzyme inhibitor, and combination of high-dose atorvastatin (80 mg) and ezetimibe (10 mg). At 6-month follow-up, the patient was asymptomatic with slightly reduced lipid parameters [Table 1]. Alternate therapies for lipid lowering were not feasible due to financial constraints.

Table 1: Lipid profile of family members

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Figure 2: Coronary angiography views. (a) LAO 60° view showing ostial severe 90% stenosis followed by proximal long-segment stenosis (70%–80%). (b) LAO 60° view showing two overlapping 3.5 mm × 28 mm drug-eluting stents (Xience V, Abbott Vascular) placed from ostium with TIMI III flow distally. (c) RAO caudal and (d) LAO caudal views showing left anterior descending artery and left circumflex artery (nondominant) with minor plaques and small caliber ramus (indicated by black arrow) with ostial total occlusion, filling retrogradely from the left system (indicated by white arrow). (LAO – Left anterior oblique; RAO – Right anterior oblique; TIMI – Thrombolysis in myocardial infarction)

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Discussion

FH was first described in 1939 by Carl Muller, showing association between cardiovascular disease, hypercholesterolemia and tendinous xanthomas due to single-gene inheritance.^[3] Cholesterol deposits in FH can involve skin of eyelids (xanthelasmas), connective tissues and extensor tendons (especially elbows, Achilles tendon, and hands, called as xanthomas), and corneal margin (corneal arcus). The most dangerous deposits occur within arteries, where they have potential to cause premature coronary artery disease, stroke, and peripheral vascular disease. According to Oosterveer et al., xanthomas and corneal arcus are pathognomonic for FH, and their presence is associated with a three-fold higher risk of cardiovascular disease in these patients.^[4]

The diagnosis of FH requires combination of history taking, physical examination, and biochemical investigations, considering which the United Kingdom Simon Broome Register [Table 2], Dutch Lipid Network and United States MEPED in area (make early diagnosis to prevent early death) have suggested diagnostic criteria.^[5],[6],[7] Simon Broome criteria [Table 2] use point scoring for family and personal history, physical signs, and mutations, in addition to the cholesterol levels, and classify patients as definite and possible diagnosis of FH.^[6]

Table 2: Simon Broome Diagnostic criteria for hypercholesterolemia

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FH is known to be associated with increased coronary heart disease and premature death unless it is diagnosed early and treated effectively.^[2] Our case was diagnosed as FH based on elevated total and LDL-C levels, multiple skin and tendon xanthomas, family history of premature cardiac death of sister, and development of premature coronary artery disease presenting as acute coronary syndrome. The presence of xanthomas since childhood and elevated total cholesterol in both parents and his sister suggests it to be a homozygous form. Genetic analysis was advised but he refused.

In view of ongoing angina, the patient was treated with early PCI and started on dual antiplatelet therapy. Considering the lipid-lowering therapy, statins are the first-line drugs followed by statin combination with other agents, such as ezetimibe, bile acid sequestrants, or stanol esters.^[8] Since the homozygous form responds less to single-drug therapy as compared to heterozygous,^[8] the index case was started on a combination of high-dose atorvastatin and ezetimibe. According to the American Heart Association, high-intensity statin therapy is targeted to reduce LDL-C approximately ≥50% from the untreated baseline.^[9] Alternate therapies are available for drug-resistant cases which include LDL-apheresis, liver transplant, and partial ileal bypass, but they lack strong supportive evidence. LDL-C apheresis typically results in a 50%–70% reduction in LDL-C levels, but it is costly, requires weekly or biweekly therapy, and has limited availability.^[10],[11] Recently, the US Food and Drug Administration has approved drugs such as lomitapide, antiproprotein convertase subtilisin/kexin type 9 (anti-PCSK9) antibody (alirocumab and evolocumab), and mipomersen sodium.^{[12],[13],[14],[15],[16]} Lomitapide (microsomal triglyceride transfer protein inhibitor) and mipomersen (an oligonucleotide antisense inhibitor directed against ApoB mRNA) are agents modifying LDL-C production by inhibiting very LDL-C secretion. However, trials show that both these drugs have side effects such as increased serum transaminases and hepatic fat which may limit their use,^[17],[18] while anti-PCSK9 antibody (evolucumab) acts by increasing LDL-C catabolism. According to RUTHERFORD-2^[19] and TESLA (part B)^[20] trials, studying evolucumab shows effective lowering levels of LDL-C in patients with both heterozygous and homozygous FH, respectively, with or without concomitant administration of cholesterol-lowering agents, thereby showing promising alternative for the treatment of FH.

Conclusion

FH can accelerate the development of coronary artery disease, leading to acute coronary syndrome at very early age. In these subset of patients, routine history taking and physical examination findings such as presence of skin and tendon xanthomas and positive family history can give clues toward the diagnosis of FH. Early diagnosis, aggressive lipid-lowering therapy, and early revascularization are required to prevent further disease-related morbidity and mortality.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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