Extracranial carotid arterial disease in patients with familial hypercholesterolemia and coronary artery disease treated with colestipol and nicotinic acid.

Abstract

Carotid bifurcation atherosclerosis was demonstrated in 34 of 108 patients with familial hypercholesterolemia and coronary artery disease by B-scan, continuous-wave Doppler sonography, and intravenous digital subtraction anglography. An intensive combined therapy of diet, colestipol, and nicotinic acid was mounted to control the hypercholesterolemia of these patients. Their serial sonographies and digital subtraction anglography were evaluated independently by technical specialists who served as coinvestigators. The data obtained suggest that 1) extracranial arterial disease can develop concurrently with coronary artery disease in a significant proportion of patients with familial hypercholesterolemia, and 2) amaurosis fugax, transient ischemic attack, cerebral infarction, and myocardial infarction did not recur during 58-72 months of control of familial hypercholesterolemia in this series of patients. Increased susceptibility to premature coronary artery disease (CAD) has been well documented. 23 There is scant information about the prevalence of extracranial carotid arterial disease in patients with familial hypercholesterolemia, particularly in those patients with known CAD. Because ultrasonography and intravenous digital subtraction angiography (IV-DSA) 4 "* have created a safe and reliable means to evaluate extracranial arterial lesions, we used these techniques to determine the possible effect of lowering cholesterol and lipid on the carotid bifurcation pathology in patients with familial hypercholesterolemia. Our goal was to determine whether long-term control of hypercholesterolemia would reduce the excess risk for stroke in a series of familial hypercholesterolemic patients with extracranial carotid arterial disease and premature CAD. Received May 15, 1985; accepted February 6, 1987. Subjects and Methods Patient PopulationOne hundred eight unselected patients with familial hypercholesterolemia and CAD (angina and/or postmyocardial infarction), aged 39-62, were evaluated. Diagnosis of heterozygous familial hypercholesterolemia was established by the demonstration of persistent hypercholesterolemia (serum total cholesterol s 300 mg/dl, LDL cholesterol ^1 9 0 mg/dl, and triglyceridê 200 mg/dl); elevated LDL cholesterol that responded minimally to a diet low in cholesterol and saturated fat; demonstration of a similar plasma lipid-lipoprotein abnormality with or without clinical CAD in firstdegree family members; and characteristic clinical manifestations of familial hypercholesterolemia including tendinous xanthomas with or without corneal arcus.3 After obtaining informed consent, 34 patients in whom extracranial carotid arterial atherosclerosis had been demonstrated were enrolled in a diet-drug treatment program for long-term management of hypercholesterolemia. Women of childbearing age and patients with secondary hypercholesterolemia or who were receiving drugs or hormones known to exert significant effects on lipid metabolism were excluded from the study. Laboratory DeterminationsDiagnosis of CAD was es...

Risk of brain infarction in familial hypercholesterolemia.

“…6 Second, in the study of Kuo et al 6 the mean decrease in serum cholesterol concentration was 42%, while in our subjects it was only 21%. Third, we followed our subjects for an average of 10 years, while the followup was 4-5 Vi years in the series of Kuo et al 6 We conclude that the risk of ischemic BI in subjects with heterozygous FH is 7.4/1000/yr, at least 20 times higher than that in the general population. Neither surgical nor conservative medical treatment of FH eliminated the risk of BI at a relatively young age in our subjects.…”

“…A good response to hypolipidemic therapy has been associated with a benign course of extracranial carotid artery disease in patients with FH. 6 In spite of the overall mean 21% decrease in serum cholesterol concentration, our subjects suffered four TIAs, four ischemic Bis, and one retinal infarction during follow-up. A mean decrease of 32% was achieved by surgical therapy compared with a mean decrease of 10% with conservative medical therapy, but the method of treatment of FH did not affect the number of new cerebrovascular events.…”

“…6 The difference may have many explanations. First, the mean serum cholesterol concentration on entry into our study was clearly higher (522 mg/dl in our study and 378 mg/dl in the series of Kuo and coworkers 6 ). Even after treatment the mean serum cholesterol concentration in our subjects remained higher than that before treatment in the patients of Kuo and coworkers.…”

“…6 The difference may have many explanations. First, the mean serum cholesterol concentration on entry into our study was clearly higher (522 mg/dl in our study and 378 mg/dl in the series of Kuo and coworkers 6 ).…”

Blood pressure treatment slows the progression of carotid stenosis in patients with isolated systolic hypertension.

“…Some studies have categorized carotid disease by use of angiography 17 or Doppler spectral analysis, 18 while others have focused specifically on changing characteristics of plaques. 19 More recently, authors have concentrated on change in intima-media thickness over time.…”