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Impaired radial artery compliance in normotensive subjects with familial hypercholesterolemia
C Giannattasio1, A A Mangoni, M Failla
1Cattedra di Medicina Interna, Università di Milano, Monza, Italy.
Insights
Familial hypercholesterolemia (FHC) significantly impairs large artery function, specifically radial artery compliance. Long-term lipid-lowering treatment with simvastatin effectively improves this vascular dysfunction in FHC patients.
Area of Science:
- Cardiovascular Medicine
- Vascular Biology
- Pharmacology
Background:
- Hypercholesterolemia is known to impair arteriolar function.
- The impact of hypercholesterolemia on large artery function, such as radial artery compliance, remains largely unknown.
- Familial hypercholesterolemia (FHC) presents a unique model to study these effects in the absence of atherosclerotic lesions.
Purpose of the Study:
- To investigate whether familial hypercholesterolemia (FHC) affects large artery function, specifically radial artery compliance (RAC).
- To assess the impact of lipid-lowering treatment on vascular abnormalities in FHC patients.
- To evaluate changes in forearm blood flow and vascular resistance following treatment.
Main Methods:
- Radial artery (RA) diameter and blood pressure (BP) were measured beat-to-beat in 13 FHC subjects and 10 controls.
- Radial artery compliance (RAC) was calculated from the diameter/BP relationship and assessed after ischemia.
- Maximal forearm blood flow and minimal forearm vascular resistance (FVR) were measured; data collected pre- and post-6 and 24 months of simvastatin treatment.
Main Results:
- Baseline RAC was significantly reduced in FHC subjects compared to controls (-53.5%).
- Ischemia induced a significant increase in RAC in controls but only a modest, non-significant increase in FHC.
- Minimal FVR was markedly higher in FHC subjects. After 24 months of simvastatin, RAC increased significantly (+55.2%) and minimal FVR decreased significantly in FHC patients.
Conclusions:
- Familial hypercholesterolemia markedly impairs not only arteriolar function but also large artery compliance and distensibility.
- This vascular impairment in FHC can be favorably influenced by effective, long-duration lipid-lowering therapy.
- Long-term simvastatin treatment demonstrates a significant positive effect on radial artery compliance and forearm vascular resistance in FHC.
Abstract:
Hypercholesterolemia impairs arteriolar dilatation, but whether the vascular abnormalities accompanying this condition include large artery function is unknown. We addressed this issue in 13 normotensive subjects with familial hypercholesterolemia (serum cholesterol 401.6 +/- 16.9 mg/dl, mean +/- S.E., FHC) and no evidence of atherosclerotic lesions, in whom radial artery (RA) diameter and blood pressure (BP) were measured beat to beat by an echotracking and a Finapres device, respectively. RA compliance (RAC) was derived from the diameter/BP relationship and expressed over the systo-diastolic BP range, both at baseline and after a 12-min brachial artery occlusion. RAC was expressed also as the area under the RAC/BP curve divided for pulse BP. Measurements included maximal forearm blood flow (plethysmography) and minimal forearm vascular resistance (FVR) which were obtained from the values following the 12-min brachial arterial occlusion. Data were collected before and after 6- and 24-month lipid lowering treatment (simvastatin 40 mg/day). Ten age-matched normotensive normocholesterolemic healthy subjects (N) served as controls. Compared to N, baseline RAC was strikingly reduced in FHC (-53.5%, P < 0.01). After ischemia RAC increased significantly and markedly in N (+38.7, P < 0.01), while only a modest and non-significant increase was observed in FHC. Minimal FVR was markedly higher in FHC than in N (3.5 +/- 0.9 vs 1.6 +/- 0.1 units, P < 0.01). In FHC (7 subjects) RAC remained unchanged after 6 months of lipid lowering treatment, but increased markedly (+55.2%, p < 0.05) when treatment was prolonged to 24 months. Lipid lowering treatment also reduced minimal FVR, the effect being significant both after 6 and after 24 months. No changes in RAC and minimal FVR were seen after 6 months in controls. Thus, in subjects with a marked increase in serum cholesterol due to FHC, not only arteriolar dilatation, but also RAC and distensibility are markedly impaired. This impairment can be favourably affected by an effective lipid lowering treatment of long duration.