Premature carotid atherosclerosis: does it occur in both familial hypercholesterolemia and homocystinuria? Ultrasound assessment of arterial intima-media thickness and blood flow velocity.

Abstract

Homocystinuria due to cystathionine beta-synthase deficiency and familial hypercholesterolemia are inherited disorders of metabolism that are associated with premature development of cardiovascular disease. This study addresses the possibility that different patterns of carotid wall damage and cerebral blood flow hemodynamics are present in these two metabolic diseases. Twelve patients with homocystinuria due to cystathionine beta-synthase deficiency (mean age, 24 years), 10 patients with homozygous familial hypercholesterolemia (mean age, 26 years), and 11 healthy control subjects (mean age, 26 years) underwent a vascular examination by noninvasive methods. B-mode ultrasound imaging was used to obtain measurements of intima-media thickness of common carotid, bifurcation, and internal carotid arteries as an index of atherosclerosis. Cerebral blood flow velocity was estimated from vascular examination of the middle cerebral artery by transcranial Doppler. Systolic, diastolic, and mean velocities were measured. Pulsatility index, a possible indicator of vascular resistance in the cerebral circulation, was also calculated. Mean maximum intima-media thickness was 1.4 mm in patients with familial hypercholesterolemia, 0.6 mm in patients with homocystinuria, and 0.6 mm in control subjects. The difference between hypercholesterolemic and homocystinuric patients or control subjects was statistically significant (P < .001). Diastolic blood flow velocities were significantly reduced in the middle cerebral arteries of hypercholesterolemic patients compared with homocystinuric patients or control subjects (P < .05), whereas systolic or mean velocities did not differ. The pulsatility index, a possible indicator of vascular resistance in the cerebral circulation, was significantly higher in hypercholesterolemic patients compared with homocystinuric patients or healthy control subjects (P < .01). A direct relation was demonstrated between pulsatility index of the middle cerebral artery and mean maximum intima-media thickness of carotid arteries on the same side (P < .001). Familial hypercholesterolemia is responsible for diffuse and focal thickening of carotid arteries and possibly also for hyperlipidemic endothelial dysfunction extending to small resistance arteries and leading to a disturbed cerebral blood flow. Patients with homocystinuria due to homozygosis for cystathionine beta-synthase deficiency seldom have plaques in their carotid arteries. They are similar to healthy control subjects with regard to both intima-media thickness and blood flow velocity in the middle cerebral artery. Therefore, it is unlikely that typical atherosclerotic lesions precede thrombotic events in homocystinuria. However, it is possible that arterial dilatations caused by medial damage lead to thrombosis in homocystinuric patients.

Carotid and Femoral Artery Wall Thickness and Stiffness in Patients at Risk for Cardiovascular Disease, With Special Emphasis on Hyperhomocysteinemia

“…Nevertheless, this positive correlation was no longer significant after adjustment for age, waist-hip ratio, serum cholesterol, smoking, and blood pressure. Rubba et al 14 found no differences between IMT in patients homozygous for homocystinuria compared with controls. This result is in accordance with that of de Valk et al, 13 who also reported no difference in IMT between heterozygous relatives of patients with homozygous homocystinuria and controls.…”

“…Until now, reports on an association of hyperhomocysteinemia with increased IMT have yielded conflicting results. [12][13][14][15][16] Furthermore, no ultrasound data are available on the effect of elevated levels of homocysteine on functional vessel wall properties. Several studies indicate that even mild hypercholesterolemia is associated with intima-media thickening, which may be reduced by cholesterol lowering.…”

Association of Obesity and Central Fat Distribution With Carotid Artery Wall Thickening in Middle-Aged Women

“…9 -12 Over the last decade, high-resolution B-mode ultrasound has been used for the noninvasive assessment of carotid intima-media thickness (IMT), a marker of early atherosclerosis. [13][14][15][16] Recently, cross-sectional carotid intimamedia (IM) area, a parameter that incorporates changes in both vessel wall and lumen diameter, has been demonstrated to be another accurate predictor of coronary atherosclerosis. 17 In the present analysis, we sought to determine whether general and abdominal obesities were associated with common carotid wall thickening in a sample of middle-aged women from Southern Italy participating in a large, ongoing, prospective study (Progetto ATENA study) designed to investigate the causes of those chronic diseases (cardiovascular disease and cancer) that have a major impact on the female population.…”

Cardiovascular risk factors and their association with carotid intima media thickness in children in Western India

“…Case control studies of children and young adults demonstrate that familial hypercholesterolemia and borderline hypertension are associated with greater IMT. [11][12][13] The young Finns study wherein children aged 3 to 18 years were re-examined 21 years later in their adulthood reported that risk factors like high levels of LDL, SBP, BMI, cigarette smoking studied in 12 to 18 years of age were directly related to CMT in adulthood.…”