Hoeks, A.P.G.

Does aortic stiffness improve the prediction of coronary heart disease in elderly the Rotterdam Study (Article)

2012-01-01T00:00:00Z

It has been demonstrated that aortic stiffness is an independent predictor of cardiovascular disease. We investigated whether this measure is of use in cardiovascular risk stratification in clinical practice for elderly subjects (mean age 71.5 years). Within the framework of the Rotterdam Study, we stratified subjects free of coronary heart disease (CHD) at baseline into categories of low (<10%), intermediate (10-20%) and high (>20%) 10-year risk of CHD based on Framingham risk factors. Within each risk category, we determined the percentages of subjects moving into a higher or lower risk category when adding aortic stiffness to the Framingham risk factors. Among 2849 participants, 223 CHD events occurred during a median follow-up of 7.9 years. In the low risk group, 5% of the subjects could be reclassified and in the high-risk group, 6% of the subjects could be reclassified to the intermediate-risk group. In the intermediate-risk group 3% could be reclassified to the high-risk group and 6% to the low-risk group. In a population of elderly subjects, aortic stiffness measurement in addition to Framingham risk factors leads to a limited reclassification of subjects in 10-year cardiovascular disease-risk categories. Therefore, aortic stiffness is associated with the risk of CHD in elderly, but provides no additional value in cardiovascular risk stratification.

Genetic variation in the fibrinogen-α and fibrinogen-γ genes in relation to arterial stiffness: The Rotterdam Study (Article)

2009-07-01T00:00:00Z

Objective: Arterial stiffness increases with age and predicts cardiovascular disease. Fibrinogen is an acute-phase protein and some studies showed an association with arterial stiffness. We studied genetic variation in the fibrinogen-α (FGA) and fibrinogen-γ (FGG) genes, by means of single nucleotide polymorphisms (FGA: -58 G/A, 1374 G/A, 1526 T/C, 312 Thr/Ala, and FGG: 4288 G/A, 6326 G/A, 7792 T/C) and resultant haplotypes in relation to arterial stiffness. Methods: The present study (n = 3891) was embedded in the Rotterdam Study. Associations of the fibrinogen level, genotypes and haplotypes with aortic stiffness (pulse wave velocity), carotid stiffness (distensibility coefficient) and pulse pressure were investigated in men and women by analyses of variance, linear regression and by haplotype analyses. Analyses were adjusted for age, mean arterial pressure, heart rate, known cardiovascular risk factors and atherosclerosis. Results: Genotype analyses yielded associations of FGA-58 G/A (P = 0.040, for trend) and FGA-1526 T/C (P = 0.004, for trend) with the fibrinogen levels, but no consistent associations with arterial stiffness, in women. FGA-haplotype 4 was associated with the fibrinogen level (P = 0.02) in women. FGA-haplotype 3 and FGG-haplotype 2 were associated with aortic stiffness (P = 0.05) in women. No associations were found in men. Conclusion: Findings indicate that the fibrinogen level and genetic variation in the FGA and FGG genes may influence arterial stiffness in women.

Genetic variation in the C-reactive protein gene and arterial stiffness: The Rotterdam Study (Article)

2008-11-01T00:00:00Z

Background and aim: Arterial stiffness increases with age and has been found to predict cardiovascular disease. C-reactive protein (CRP) is an inflammation marker and has been found to be associated with arterial stiffness and risk of cardiovascular disease. Genetic factors account for part of the variance in CRP level. We studied the association of the total common variation in the CRP gene by polymorphisms 1184 C/T, 2042 C/T, 2911 C/G and haplotypes with arterial stiffness within the Rotterdam study. Methods: The study (n = 3615) was embedded in the Rotterdam Study, a prospective, population-based study among subjects aged 55 years and older. Associations of genotypes and haplotypes with CRP level and measures of arterial stiffness were examined using linear regression and analyses of variance. Measures of arterial stiffness included aortic pulse wave velocity, carotid distensibility and pulse pressure. Analyses were adjusted for age, sex, mean arterial pressure, heart rate, known cardiovascular risk factors and measures of atherosclerosis. Results: CRP level was significantly associated with pulse wave velocity (p < 0.001) and pulse pressure (p < 0.05), also after adjusting for cardiovascular risk factors. CRP level was also associated with the 1184 C/T (T-allele: higher level), the 2042 C/T (T-allele: lower level) and 2911 C/G (G-allele: higher level) polymorphisms (all p < 0.001). Genotype and haplotype analyses showed no consistent associations of genetic variation with pulse wave velocity, carotid distensibility and pulse pressure. Conclusions: No consistent associations of the CRP polymorphisms 1184 C/T, 2042 C/T, 2911 C/G and corresponding haplotypes were found with measures of arterial stiffness.

Arterial stiffness, cardiovagal baroreflex sensitivity and postural blood pressure changes in older adults: The Rotterdam Study (Article)

2007-07-01T00:00:00Z

OBJECTIVE: Arterial stiffness may be involved in the impairment of the arterial baroreflex. In the present study the associations between arterial stiffness and cardiovagal baroreflex sensitivity (BRS) and between BRS and postural blood pressure (BP) changes were investigated within the framework of the Rotterdam Study. METHODS: Arterial stiffness was determined by aortic pulse wave velocity and the carotid distensibility coefficient. Continuous recording of the R-R interval and finger BP was performed with the subject resting supine, and BRS was estimated from the spontaneous changes in systolic BP and corresponding interbeat intervals. Measures of aortic stiffness or carotid distensibility and BRS were available in 2490 and 2083 subjects, respectively. The association between arterial stiffness and ln BRS was investigated by multivariate linear regression analysis and then by analysis of covariance, comparing BRS by quartiles of arterial stiffness. RESULTS: The mean age of the subjects was 71.7 ± 6.6 (41.7% men). Aortic stiffness was negatively associated [β = -0.029; 95% confidence interval (CI): -0.040, -0.019] and the carotid distensibility coefficient positively associated with BRS (β = 0.017; 95% CI: 0.010, 0.024). An orthostatic decrease in systolic BP was absent in 1609 subjects, between 1 and 10 mmHg in 502 and >10 mmHg in 269 subjects, with corresponding mean values (95% CI) of ln BRS of 1.47 (1.44-1.51), 1.43 (1.37-1.49) and 1.36 (1.28-1.44) ms/mmHg (test for trend P < 0.019). An orthostatic decrease in diastolic BP was absent in 1123 subjects, 1-10 mmHg in 1057 and >10 mmHg in 209 subjects, with corresponding mean values of ln BRS of 1.49 (1.45-1.53), 1.41 (1.37-1.45) and 1.45 (1.36-1.54) ms/mmHg (P < 0.04). CONCLUSION: In a large population of older subjects, arterial stiffness appears to be an independent determinant of impaired BRS. Within the same population, impaired BRS was associated with orthostatic BP changes.

TGF-β1 polymorphisms and arterial stiffness; the Rotterdam Study (Article)

2007-06-01T00:00:00Z

Arterial stiffness is a risk factor for cardiovascular disease. Transforming growth factor β1 is a pleiotropic cytokine, with many functions, including influence on the vascular wall (e.g., on angiogenesis, endothelial cells and the extracellular matrix). We investigated five functional polymorphisms in the transforming growth factor β1 gene (-800 G/A, -509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro and codon 263 Thr/Ile) in relation to arterial stiffness in a population-based study. A total of 3863 participants of the Rotterdam Study, a prospective population-based study, were included in the current study. The relations of the genotypes and haplotypes with arterial stiffness (pulse wave velocity (PWV), distensibility coefficient (DC) and pulse pressure (PP)) were studied using analyses of variance and linear regression. The analyses were adjusted for age, sex, mean arterial pressure, heart rate, conventional cardiovascular risk factors and measures of atherosclerosis. There were no associations between PWV and -800 G/A (P = 0.56), -509 C/T (P = 0.29), codon 10 (P = 0.98) and, codon 25 (P = 0.28). These polymorphisms were not associated with the DC or with PP. The haplotype-based analyses yielded similar results. The results of this study show that the TGF-β1 -800 G/A, -509 C/T, codon 10 Leu/Pro and codon 25 Arg/Pro polymorphisms are not associated with arterial stiffness.