Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease that leads to the increase of low density lipoprotein (LDL) cholesterol [1]. It comes in two forms of different severity. The FH heterozygous affects 1/200 to 1/500 subjects. The homozygous form, more severe, affects one in a million [2].

Although acute rheumatoid arthritis has long been the most frequent source of aortic stenosis (AS), the valvular sclerosis, so-called degenerative, is now the predominant etiology. This form of AR has long been regarded as a degenerative process linked to aging, of which it was therefore difficult to modify evolution. However, recent studies show that this disease has many similarities to atherosclerotic coronary artery disease (ACAD) in both pathophysiology and risk factor, suggesting that AS is in fact only one of the many manifestations of atherosclerosis [3]. However, in Africa, the etiology of aortic stenosis is dominated by acute rheumatic fever. We report the case of a patient with aortic stenosis probably related to a heterozygous FH.

He was a patient of 24 years, male, followed in dermatology for tuberous xanthomas. Physical examination revealed a NYHA's stage III dyspnea. Familial history did not show any similar case with his mother and sister. His father died of unknown causes. Cardiac auscultation had highlighted a midsystolic murmur 4/6 at aortic area irradiating at the neck's vessels and an abolition of B2. There was no peripheral sign of cardiac decompensation. Blood pressure was 120/65 mm Hg in the right arm and 100/60 mmHg in the left arm and the resting heart rate was of 51 beats/min. The electrocardiogram showed regular sinus rhythm and left ventricular hypertrophy with disturbances of repolarization type of ischemia subepicardial in apical-lateral. In biology, we found hypercholesterolemia with levels of total cholesterol at 6.23 g/l and LDL cholesterol at 5.42 g/l. HDL cholesterol was 0.62 g/l and triglycerides 0.70 g/l. The Doppler echocardiography concluded a very severe aortic stenosis on highly calcified tricuspid aortic valves, with an aortic area of 0.6 cm²/m² of body surface area calculated by continuity equation, an average gradient of 68 mmHg, a maximum speed of aortic flow at 5.35 m/s and a permeability index at 19% (Figure 1). There were no other valvular abnormalities. Ejection fraction of the left ventricle was normal. The coronarography objectified a coronary network moderately atheromatous without angiographically significant lesions (Figure 2). The dermatological examination showed tuberous xanthomas as nodular lesions sitting at the pressure areas (elbows, knees and buttocks) measuring 8 cm, painless, taking a tumor-like appearance of reddish color (Figure 3). Ophthalmologic examination showed corneal arc in both eyes. His treatment associated lipid-lowering diet, statins at high doses (atorvastatin 80 mg/day) and loop and potassium sparing diuretics. The patient is waiting for surgery for aortic valvular replacement. The opportunity to take a sample for histopathological analysis will be exploited during the gesture.

Figure 1: A: Transthoracic echocardiography parasternal short axis showing calcifications of aortic valve with reduced opening, B: Continuous-wave Doppler measurement of mean gradient, C: Pulsed-wave Doppler measurement of aortic valve area.

Figure 2: Coronary angiography showing normal arteries.

Figure 3: Tuberous xanthomas located at pressure areas.

Familial hypercholesterolemia is due to biological alteration of a pathogenic mutation carried by a single gene of the LDL receptor (LDLR). Other mutations were recently identified as the genes coding for ApoB, the LDLRAP1 (LDL receptor adapter protein 1) and PCSK9 (pro-protein concertase subtilisin / Kexin Type 9) [4,5]. Genetic analysis provides a definitive diagnosis and facilitates family screening. Given the complexity and the cost of the procedure, this genetic analysis was not performed on our patient and his siblings. However, this analysis has limitations with a low probability to identify the mutation [6,7]. Patients with FH have a long-term high risk for a cardiovascular disease which is of the order of 20 to 40% [8,9]. Valvular sclerosis has long been considered a degenerative process associated with aging. However, recent studies show that this disease has many similarities with atherosclerotic heart disease both in terms of the pathophysiology and of the risk factors suggesting that the AS would be one of the many manifestations of atherosclerosis [3,10,11]. The treatment of FH has the main purpose of reducing mortality and the effects of the atherosclerotic cardiovascular disease by reducing plasma LDL levels [1,12,13]. The therapeutic treatment in our patient consisted of a lipid-lowering diet associated with statins. Although it has a partial efficacy, association with ezetimibe or sequestering bile acids agents was not possible due to lack of availability. LDL apheresis would have been a treatment of choice for our patient, but was, unfortunately, not available.

The AS has long been seen as a purely degenerative disease. The results presented in this article, however, support the concept that AS is an active disease that has many similarities with atherosclerosis and, therefore, likely to be altered by changes in feeding behaviors and/or pharmacological interventions.