Biomedical subjects

Eric de Groot

Publications and source records attributed to Eric de Groot.

25 records · Page 2Linked to original sources

PubMed2003

Surrogate markers of atherosclerosis: impact of statins.

Carotid artery intima-media thickness (IMT) measured by ultrasound has been shown to be correlated with existing cardiovascular disease (CVD) and predictive of CVD in individuals without clinically evident disease. Carotid IMT is now widely used as a surrogate marker for atherosclerotic disease. A number of studies have shown that lipid-lowering therapy with a statin can reduce or reverse carotid IMT progression. The METEOR trial (Measuring Effects on Intima-Media Thickness: an Evaluation Of Rosuvastatin) will examine the effects of aggressive lipid-lowering treatment with rosuvastatin on IMT in mildly hypercholesterolemic low-risk subjects with relatively high IMT values. The results will provide important information on the ability to achieve regression of abnormal IMT with robust reductions in low-density lipoprotein (LDL) cholesterol levels to below current target levels. Another study will examine the effects of potent LDL cholesterol reduction with rosuvastatin in young patients with heterozygous familial hypercholesterolemia (FH). Patients with FH are at increased risk of premature coronary heart disease in association with marked LDL cholesterol elevations, exhibiting a rate of progression of IMT 5x greater than that of low-risk controls without the disorder and early intervention may be the optimal approach to modifying atherosclerosis progression in these patients.

Biomarkers↗

PubMed2003

The significance of femoral intima-media thickness and plaque scoring in the Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP) study.

BACKGROUND: Measurement of intima-media thickness (IMT) is a well established surrogate marker for cardiovascular endpoints. We studied the long-term effects of statins on femoral IMT and plaque scoring in the Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP) study. METHODS AND RESULTS: Three hundred and twenty-five patients with familial hypercholesterolaemia were randomized to either atorvastatin 80 mg/day or simvastatin 40 mg/day. IMT was measured at baseline and at 2 years. At baseline, femoral IMT was 1.69 mm in the atorvastatin group and 1.61 mm in the simvastatin group; at 2 years, IMT increased by 0.06 mm (P=0.24) and 0.15 mm (P=0.012), respectively. No significant differences were obvious between these two treatment arms (P=0.26). Femoral plaques were present in 64.7% in the atorvastatin group and 56.1% in the simvastatin group at baseline; after 2 years, these proportions rose to 66.0% (P=0.47) and 67.3% (P=0.02), respectively (P=0.87 between treatment arms). Carotid plaques were present in 6.3% versus 4.9%; after 2 years, these percentages were 5.0% (P=0.48) versus 5.5% (P=0.71), respectively (P=0.90 between treatment arms). CONCLUSION: Our study indicates increased efficacy of atorvastatin 80 mg in retarding progression of atherosclerosis in the femoral artery compared with simvastatin 40 mg. Interestingly, in the carotid arteries these statins influenced IMT to a greater extent, whereas in the femoral artery the effects were more pronounced on plaque frequency. These findings underscore the generalized effects of lipid lowering on atherosclerosis.

Anticholesteremic Agents↗

PubMed2002

Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux: an observational study.

BACKGROUND: Decreased concentrations of HDL cholesterol are associated with increased cardiovascular risk. These concentrations are directly related to cholesterol efflux from cells-the first step and a key process in reverse cholesterol transport. Cholesterol efflux is mediated by the ATP-binding cassette A1 transporter (ABCA1), the rate-limiting step in the production of HDL. We aimed to assess the relation between cholesterol efflux, HDL concentrations, and arterial-wall changes in individuals with impaired ABCA1 function. METHODS: We investigated 30 individuals from families with ABCA1 mutations, and 110 controls matched for age, sex, and ethnic origin. We measured concentrations of HDL cholesterol in plasma and intima-media thickness of the carotid arteries by B-mode ultrasonography in all participants. We also measured cholesterol efflux from skin fibroblasts in nine individuals with ABCA1 mutations and in ten controls. FINDINGS: Individuals with ABCA1 mutations had lower amounts of cholesterol efflux, lower HDL cholesterol concentrations, and greater intima-media thicknesses than controls. An intima-media thickness at the upper limit of normal (0.80 mm) was reached by age 55 years in the ABCA1 heterozygotes, and at age 80 years in unaffected controls (p<0.0001). Additionally, strong positive correlations were seen between HDL cholesterol concentrations and cholesterol efflux (r=0.90, p=0.001), and negative correlations between apolipoprotein-AI-mediated (r=-0.61, p=0.030) and HDL-particle-mediated (r=-0.60, p=0.018) efflux and intima-media thickness in the ABCA1 mutation carriers. INTERPRETATION: These results show a direct relation between ABCA1-mediated cellular cholesterol efflux and arterial-wall thickness, and therefore suggest that increasing efflux could inhibit atherosclerosis progression before the manifestation of symptomatic cardiovascular disease.

ATP Binding Cassette Transporter 1↗

PubMed2002

Arterial wall thickness and the risk of recurrent ischemic events in carriers of the prothrombin G20210A mutation with clinical manifestations of atherosclerosis.

The G20210A mutation in the prothrombin gene is an established risk factor for venous thrombosis. There is controversy about the role of this mutation in arterial thrombotic disease and atherosclerosis. We determined the presence of the prothrombin mutation and examined its influence on carotid and femoral artery intima-media thickness (IMT) and the occurrence of new ischemic events during follow-up in 277 patients with clinically manifest atherosclerotic disease: ischemic stroke, myocardial infarction or peripheral arterial disease. The mean age at entry was 63 years. Mean IMT was significantly higher in carriers of the prothrombin mutation (1.17 (SD 0.29) mm versus 0.97 (SD 0.25) mm: (delta)IMT=0.20, P=0.02). The increase in IMT was not attributable to differences in age, type of arterial disease or cardiovascular risk factors between carriers and non-carriers. During a mean follow-up of 3.5 years, a strong trend for more ischemic events was observed: 4 of the 11 carriers suffered from a recurrent ischemic event, compared with 30 of the 164 male non-carriers (36 versus 18%; P=0.06). These results suggest that the G20210A mutation contributes to the process of arterial wall thickening and is associated with the occurrence of ischemic events in a cohort of elderly persons with established atherosclerosis.

Aged↗

PubMed2002

Measurement of subclinical atherosclerosis: beyond risk factor assessment.

PURPOSE OF REVIEW: Assessment of subclinical atherosclerosis using the current available noninvasive imaging modalities holds promise for individual cardiovascular risk management and monitoring efficacy of therapeutic interventions (i.e. surrogate end-points). The present review addresses benefits and limitations of flow-mediated dilatation, intima-media thickness, electron-beam computed tomography and magnetic resonance coronary angiography. RECENT FINDINGS: Both carotid intima-media thickness and peripheral flow-mediated dilatation correlate inversely with cardiovascular risk factors and coronary artery disease. They have been shown to carry predictive value for future cardiovascular events, but clinical application of both intima-media thickness and flow-mediated dilatation demands further methodological maturation of these techniques. Intima thickening has been successfully targeted in numerous intervention trials, but determination of an explicit threshold value beyond which cardiovascular risk significantly increases will facilitate its utility as a routine clinical tool. Electron-beam computed tomography can accurately detect and quantify coronary artery calcification (an established marker of the total coronary plaque burden). However, lack of evidence of its additional predictive power for future coronary events warrants for further research. Finally, magnetic resonance coronary angiography appears to be a promising technique, integrating both functional and anatomical aspects of coronary artery disease. Properly designed studies are needed to determine its value in clinical practice. SUMMARY: Various noninvasive imaging techniques have recently emerged that may find applications in clinical research. However, before widespread clinical utilization, further technical refinement of all of the cited imaging modalities is mandatory. It will be a challenge over the coming few years to clarify whether improvements in surrogate end-points can directly be translated into improved outcomes.

Blood Flow Velocity↗

PubMed2002

Increased arterial stiffness in young adults with end-stage renal disease since childhood.

Increased arterial stiffness is a risk factor for mortality in adults over 40 yr of age with end-stage renal disease (ESRD). As no data exist on vascular changes in young adults with ESRD since childhood, a long-term outcome study was performed. All living Dutch adult patients with onset of ESRD between 1972 and 1992 at age 0 to 14 yr were invited for carotid artery and cardiac ultrasound and BP measurements. Data on clinical characteristics were collected by review of all medical charts. Carotid ultrasound data were compared with those of 48 age-matched and gender-matched healthy controls. Carotid artery and cardiac ultrasound was performed in 130 out of 187 eligible patients. Mean age was 29.0 (20.7 to 40.6) yr. Compared with controls, patients had a similar intima media thickness but a reduced mean arterial wall distensibility DC (40.0 versus 45.0 kPa(-1). 10(-3); 95% CI, -9.1 to -0.8; P < 0.001), an increased stiffness parameter beta (4.2 versus 3.8; 95% CI, 0.05 to 0.68; P = 0.02), an increased elastic incremental modulus E(inc) (0.35 versus 0.27 kPa. 10(3); 95% CI, 0.02 to 0.12; P < 0.001). Multiple regression analyses in all subjects revealed that ESRD was associated with an increase in beta and E(inc). Arterial wall properties of patients currently on dialysis and transplanted patients were comparable. In all patients, current systolic hypertension was associated with increased E(inc) and decreased DC. In conclusion, carotid arterial wall stiffness is increased in young adult patients with pediatric ESRD. Hypertension is a main determinant and might be a target for treatment of these potentially lethal arterial wall changes.

Adult↗

PubMedDate not supplied

Regression of carotid and femoral artery intima-media thickness in familial hypercholesterolemia: treatment with simvastatin.

OBJECTIVE: To investigate whether high-dose simvastatin therapy could reduce carotid and femoral artery intima-media thickness (IMT) in patients with familial hypercholesterolemia (FH) to prevent cardiovascular disease. BACKGROUND: Imaging of arterial walls with B-mode ultrasonography is increasingly used as a noninvasive surrogate marker of cardiovascular disease. Intervention trials using this modality have shown that by reducing risk factors, progression of atherosclerosis was inhibited. METHODS: After a washout period of 6 weeks, all patients with FH started monotherapy with simvastatin, 80 mg/d, for 2 years. The primary end point was the change (in millimeters) of the mean combined far-wall IMT of predefined carotid and femoral arterial segments at 2 years. RESULTS: We included a total of 153 patients with FH. Mean +/- SD combined baseline IMT was 1.07 +/- 0.23 mm. After treatment with simvastatin for 2 years, this IMT decreased by a mean of 0.081 mm (95% confidence interval, -0.109 to -0.053; P<.001), with its largest reduction in the femoral artery (-0.283 mm; P<.001). An actual decrease of combined IMT was seen in 69.8% of all patients. CONCLUSIONS: High-dose simvastatin therapy reduces arterial wall IMT in more than two thirds of the patients, with its largest effect on the femoral artery. Furthermore, patients with FH who were treated with both statin and antihypertensive medication experienced a significantly greater benefit in terms of IMT reduction.

Adult↗