A “didactic” Familial Combined Hyperlipoproteinemia case report with a early total occlusion of the right carotid.

Arrigo FG Cicero, Simona Nascetti, Egidio Pedro, Sergio D’Addato, Antonio Gaddi

Atherosclerosis Study Centre ”G. Descovich”  – Dept. of Clinical Medicine and Applied Biotechnology “D. Campanacci” - University of Bologna – Italy

 

Introduction

Familial Combined Hyperlipoproteinemia (FCH) is an inherited disorder of the lipid metabolism characterised by an increase in cholesterolemia and/or triglyceridemia in more relatives of the same family. It is associated with a strongly increased risk of premature coronary heart disease (CHD) and is typically characterised by intraindividual and intrafamilial variability of the lipid phenotype. FCH prevalence, estimated in general population, varies between 0.3 and 2%, while it is the most frequent genetic disorder in patients with CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%); the prevalence increases up to 40% if all the myocardial infarction survivors are considered (1). The aim of this report is to present a typical serious clinical case of an FCH patient that obtained a diagnosis only in a very late stage of his disease when its typical (and serious) consequences are already present.

Case report

We report about a Caucasic patient, 51 years old, BMI= 25.95, affected by FCH associated to border-line hypertension and diabetes mellitus from the last year, these last two being FCH typical consequences (2). In his family, we found histories of hypercholesterolemia and/or hypertriglyceridemia, diabetes and cerebrovascular disease. During the last 20 years it has never been adequately treated because of its extremely variable plasma lipid levels that often touched normal values, so that different physicians believed that the subject did not adequately followed the diet (average plasma LDL-C level= 299±91 mg/dL, range= 199-418 mg/dL; average plasma TG level= 278±115 mg/dL, range= 145-526 mg/dL). Other routine laboratory values were always normal. Physical examination is normal: no signs of systemic disorders are evident. Blood pressure is: 140/90 and  pulse rate 85/minute. Abdominal ultrasound exam highlights a colelythiasis. Stress electrocardiogram is negative for ischemic signs and the patients did not experienced angina nor dyspnoea, without ischemia induced S-T level change. However, eco-colour Doppler shows extensive atheromasia in both right and left common carotids and carotids bifurcations, total occlusion of the right internal carotid at the origin (Figure 1) associated to a concentric stenosis of the right external carotid. The concentric stenosis at the left external carotid level was of the 65%, while at both right and left succlavia and vertebral arteries of 40%. Stenosis was absent at arterial inferior limbs and abdominal aorta  it was evident absence of stenosis

The transcranial doppler ultrasonography found an asymmetry of blood velocity end pulsatiliy index of middle cerebral arteries (right<left). Right middle cerebral artery is revascularizated by the controlateral inferior cerebral artery through activation of the left anterior compensation towards the right.

The right middle cerebral artery blood velocity was 30 cm/sec (in apnoea 48), the left one 50 cm/sec (in apnoea 68), respectively. Right pulsatility index was 0.92, the left one 1.15, respectively.

The right carotid siphon blood velocity and pulsatility index were 40 cm/sec and 0.84, respectively, the left carotid siphon ones 58 cm/sec and 1.19, respectively.

Blood velocity in right and left posterior, anterior, vertebral, and basilar cerebral arteries was 38 cm/sec, 40 cm/sec, 70 cm/sec, 68 cm/sec, 38 cm/sec, 40 cm/sec, 44 cm/sec and 44 cm/sec.

Discussion

The transcranial Doppler ultrasonography permits noninvasive quantification of the cerebral hemodynamic consequences of internal carotid artery occlusion and direct evaluation of the collateral blood supply (3). In this patient the right carotid occlusion has been totally compensated by collateral intracerebral arteries, so that he is totally asymptomatic. However, as many other FCH serious patients, he has not received an adequate diagnosis and a treatment for the metabolic disease that causes this wide atheromasia. Therefore, FCH diagnosis could be difficult, even because of the lack of agreement between the plasma lipid-based criteria and apolipoprotein B for the diagnosis of familial combined hyperlipidemia (4).

Considering the blood pressure and plasma lipid levels found during a year when the patient has been totally untreated, and when he 46 year old, he was still not hypertensive nor diabetic, we calculated their coronary, cerebrovascular, and cardiovascular disease estimated risk, relative risk, and the biologic age with the Riscard 2002 software (5). During those year his plasma total cholesterol level varied within a range of 158 mg/dl (245-403 mg/d), the coronary, cerebrovascular, and cardiovascular disease estimated risks varied respectively in a range of 15.10 (9-24.10), 16.7 (1.30-18), and 11.9 (11.7-23.6); the relative risks varied respectively in a range of 5.25 (0.10-5.35), 1.58 (2.08-3.66), and 1.52 (1.87-3.39); the biologic age varied in the range of 10 (47-57), 6 (44-50) and 7 (45-52) years.

Conclusion

Cardiovascular risk of FCH patients is hardly estimable with standard risk stratification means. Thus, many FCH patients could be not adequately treated until the appearance of serious atherosclerosis complication as the early total occlusion of a carotid.

References     

1.    Gaddi A, Galetti C, Pauciullo P, Arca M. Familial combined hyperlipoproteinemia: experts panel position on diagnostic criteria for clinical practice. Committee of experts of the Atherosclerosis and Dysmetabolic Disorders Study Group. Nutr Metab Cardiovasc Dis. 1999;9(6):304-11.

2.    Keulen ET, Voors-Pette C, de Bruin TW. Familial dyslipidemic hypertension syndrome: familial combined hyperlipidemia, and the role of abdominal fat mass. Am J Hypertens 2001;14(4 Pt 1):357-63

3.    Schneider PA, Rossman ME, Bernstein EF, Torem S, Ringelstein EB, Otis SM. Effect of internal carotid artery occlusion on intracranial hemodynamics. Transcranial Doppler evaluation and clinical correlation. Stroke 1988;19(5):589-93

4.    Jarero JP, Aguilar-Salinas CA, Guillen-Pineda LE, Perez FJ, Rull JA. Lack of agreement between the plasma lipid-based criteria and apoprotein B for the diagnosis of familial combined hyperlipidemia in members of familial combined hyperlipidemia kindreds. Metabolism 2002;51(2):218-24

5.    Menotti A, Lanti M, Puddu PE, et al. The risk functions incorporated in Riscard 2002:a software for the prediction of cardiovascular risk in the general population based on Italian data. Ital Heart J 2002;3(2):114-21.

 

Figure 1 – Totally occluded right internal carotid origin of an asymptomatic FCH patient