Effects of initial and long-term lipid-lowering therapy on vascular wall characteristics

Ubels, F.L.; Muntinga, J.H.J.; Doormaal, Jasper J. van; Reitsma, Wd; Smit, Andries J.

doi:10.1016/s0021-9150(00)00450-0

Cited by 22 publications

(18 citation statements)

References 23 publications

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“…The development of an increased stiffness of the microvessel wall in many models of hypertension (3,8,18,21,22,28), diabetes mellitus (3,7,21,22,26), and to some extent dyslipidemia (21,22,26,30) has been demonstrated previously. However, that this increased stiffness was associated with a thinning of the vessel wall (i.e., a lack of a net hypertrophic response) and a reduced cross-sectional wall area is novel and suggests that remodeling of individual microvessels in OZR may be far more complicated than that which develops in the face of chronic elevations in perfusion pressure alone.…”

Section: Discussionmentioning

confidence: 53%

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats

Frisbee

2003

American Journal of Physiology-Heart and Circulatory Physiology

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Whereas previous studies have demonstrated that the development of syndrome X in obese Zucker rats (OZR) is associated with impaired arteriolar reactivity to vasoactive stimuli, additional results from these studies indicate that the passive diameter of skeletal muscle arterioles is reduced in OZR versus lean Zucker rats (LZR). On the basis of these prior observations, the present study evaluated structural alterations to the skeletal muscle microcirculation as potential contributors to an elevated vascular resistance. Isolated skeletal muscle resistance arterioles exhibited a reduced passive diameter at all levels of intralumenal pressure and a left-shifted stress-strain curve in OZR versus LZR, indicative of structural remodeling of individual arterioles. Histological analyses using Griffonia simplicifolia I lectin-stained sections of skeletal muscle demonstrated reduced microvessel density (rarefaction) in OZR versus LZR, suggesting remodeling of entire microvascular networks. Finally, under maximally dilated conditions, constant flow-perfused skeletal muscle of OZR exhibited significant elevations in perfusion pressure versus LZR, indicative of an increased resistance to perfusion within the microcirculation. These data suggest that developing structural alterations to the skeletal muscle microcirculation in OZR result in elevated vascular resistance, which may, acting in concert with impaired arteriolar reactivity, contribute to blunted active hyperemic responses and compromised performance of in situ skeletal muscle with elevated metabolic demand.

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Section: Discussionmentioning

confidence: 53%

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats

Frisbee

2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…It is also possible that the time course and magnitude of plaque regression are directly proportional or easier to detect in patients with greater baseline burden, as suggested by studies in patients with as opposed to those without familial hypercholesterolemia, 10 as well as studies using the femoral wall thickness as opposed to carotid wall thickness measured by ultrasound. 10,16,27 Our understanding of atherosclerotic plaque regression is largely derived from pathological studies performed in experimental animals 21,28 -31 and humans. 14,32 There is a large body of evidence indicating that atherosclerotic plaque lipid content is depleted with plasma cholesterol reduction 14 and that such reduction can be monitored experimentally by MRI.…”

Section: Discussionmentioning

confidence: 99%

Statin-Induced Cholesterol Lowering and Plaque Regression After 6 Months of Magnetic Resonance Imaging–Monitored Therapy

et al. 2004

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Background-Statin therapy reduces adverse outcomes, with a minimal decrease in vessel stenosis. Magnetic resonance imaging (MRI) noninvasively detects atherosclerotic plaque (AP) reduction. We hypothesized that statin-induced AP regression can be monitored by MRI and detected earlier than previously reported and is significantly associated with its lipid-lowering effect. Methods and Results-APs in thoracic aorta were measured by combined surface/transesophageal MRI in 27 patients (treated with simvastatin 20 to 80 mg daily) before and after 6 months of therapy. AP volume and luminal dimensions were measured from 6 cross sections used to construct a 2.4-cm 3D volume of the aorta that included plaque and lumen. Method reproducibility was studied in 10 patients imaged twice, 1 week apart. AP volume was reduced from 3.3Ϯ0.1.4 to 2.9Ϯ1.4 cm 3 at 6 months (PϽ0.02), whereas luminal volume increase was less accentuated (from 12.0Ϯ3.9 to 12.2Ϯ3.7 cm 3 , PϽ0.06). LDL cholesterol decreased by 23% (from 125Ϯ32 to 97Ϯ27 mg/dL, PϽ0.05) in 6 months. AP regression (plaque volume/area reduction) was significantly related to LDL cholesterol reduction (PϽ0.02 and PϽ0.005, respectively), and luminal volume increase was inversely related to LDL cholesterol reduction (PϽ0.04). Plaque volume measurement was highly reproducible (intraclass correlation Rϭ0.98 and variabilityϭ4.8%). Intraobserver (0.91) and interobserver (0.81) concordances were documented for plaque volume assessment. Conclusions-AP regression and reverse remodeling can be detected accurately by MRI 6 months after statin therapy initiation, and it is strongly associated with LDL cholesterol reduction.

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“…11 In addition, the long-term administration of statins has been shown to inhibit the progression of aortic stenosis 12 and to reduce aortic stiffness, as assessed by PWV, in normotensive patients with hypercholesterolaemia. 13,14 Therefore, long-term statin administration may improve BP control and PWV in patients with uncontrolled hypertension and high serum cholesterol levels. However, a recent study reported that 12-week atorvastatin treatment worsened PWV in hypertensive hyperlipidaemic patients.…”

Section: Introductionmentioning

confidence: 99%

Long-term effects of statins on arterial pressure and stiffness of hypertensives

et al. 2004

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Although lowering blood pressure (BP) reduces aortic stiffness, achieving the recommended BP goal can be difficult. Recent studies have shown that short-term use of statins can reduce BP significantly. To determine the long-term effects of statins on BP and aortic stiffness, a single-blind randomized prospective study was performed on 85 hyperlipidaemic hypertensive patients whose BP was insufficiently controlled by antihypertensive therapy. Every 3 months, aortic stiffness was assessed by measuring pulse wave velocity (PWV). Patients were randomly allocated to groups treated with pravastatin, simvastatin, fluvastatin, or a nonstatin antihyperlipidaemic drug. No significant differences in patient characteristics, kinds of antihypertensive drugs, BP, ankle brachial index, PWV, or serum lipid, creatinine, or C-reactive protein levels were found between the four groups at the start of the study. During the 12-month treatment period, PWV did not change in the pravastatin group or nonstatin group, but it was transiently reduced in the simvastatin group and significantly decreased in the fluvastatin group, even though the doses of the statins used in this study were lower than the usually prescribed dose. All four antihyperlipidaemic drugs significantly decreased serum cholesterol levels without affecting BP, ankle brachial index, or serum triglyceride levels. The Creactive protein serum levels decreased significantly in the three statin groups but not in the nonstatin group. These results suggest that long-term use of fluvastatin by hyperlipidaemic hypertensive patients is associated with a significant reduction in aortic stiffness without any effect on BP.

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Effects of initial and long-term lipid-lowering therapy on vascular wall characteristics

Cited by 22 publications

References 23 publications

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats

Statin-Induced Cholesterol Lowering and Plaque Regression After 6 Months of Magnetic Resonance Imaging–Monitored Therapy

Long-term effects of statins on arterial pressure and stiffness of hypertensives

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