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ABSTRACT: Non-invasive measures of atherosclerosis, such as carotid intima-media thickness (cIMT), may improve global cardiovascular risk prediction. The aim of this study was to determine whether common carotid IMT in addition to traditional risk factors improves risk classification in a general population of older people.
A group of 3580 non-diabetic people aged 55-75 years and free of cardiovascular disease at baseline were followed for a median time of 12.2 years. Compared to models based on Framingham risk factors, we studied the ability of common cIMT measurement to better classify people into categories of low (<10%), intermediate (10-20%) and high (>20%) 10-year risk of hard coronary heart disease (CHD) and stroke. In older men, addition of cIMT to Framingham risk factors did not improve prediction of hard CHD or stroke. In older women, addition of cIMT to Framingham risk factors significantly improved risk classification. cIMT improved the C-statistic of the model for hard CHD from 0.711 to 0.719 and for stroke from 0.712 to 0.721, at good calibration. Reclassification was least in the majority of women classified as low risk (4% (n = 76) for hard CHD and 3% (n = 62) for stroke) and most substantial in women at intermediate risk (43% (n = 70) for hard CHD and 28% (n = 76) for stroke). The net reclassification improvement in women was 8.2% (p = 0.03) for hard CHD and 8.0% (p = 0.06) for stroke.
cIMT had some additional value beyond traditional risk factors in the cardiovascular risk stratification of older women, but not of older men.
European journal of preventive cardiology. 06/2011; 19(4):698-705.
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ABSTRACT: Previous cross-sectional studies found an association between inflammatory markers and measures of arterial stiffness. Recently, some studies investigated whether patients with genotypes associated with high levels of circulating C-reactive protein had high arterial stiffness. These studies reported an association between C-reactive protein levels and measures of arterial stiffness, but no association between polymorphisms in the C-reactive protein gene and arterial stiffness, suggesting that C-reactive protein may have no causal role in the development of arterial stiffness. To further investigate the nature of the association between inflammatory markers and arterial stiffness, we prospectively examined the association of high-specificity C-reactive protein with incident-isolated systolic hypertension, as a model of arterial stiffness, in a large population-based study.
The present study included 1637 apparently healthy participants from the Rotterdam study. The mean age of the participants was 64 +/- 6.4 years. During follow-up, 252 participants developed isolated systolic hypertension. Logistic regression analyses were performed. One standard deviation of high-specificity C-reactive protein was associated with incident-isolated systolic hypertension [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01-1.41].
The findings of the present study support a role of C-reactive protein in the development of isolated systolic hypertension in apparently healthy older adults.
Journal of hypertension 04/2010; 28(5):892-5. · 4.02 Impact Factor
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Mark PS Sie,
Aaron Isaacs,
Moniek PM de Maat, Francesco US Mattace-Raso,
André G Uitterlinden,
Isabella Kardys,
Albert Hofman,
Arnold PG Hoeks,
Robert S Reneman,
Cornelia M van Duijn,
Jaqueline CM Witteman
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ABSTRACT: 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.
Journal of Hypertension 06/2009; 27(7):1392-1398. · 4.02 Impact Factor
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Journal of Hypertension 12/2008; 26(11):2251-2. · 4.02 Impact Factor
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ABSTRACT: Aortic stiffness is an independent predictor of cardiovascular morbidity and mortality. We investigated whether aortic stiffness, estimated as aortic pulse wave velocity, is associated with decreased perfusion pressure estimated as the cardiac oxygen supply potential.
Aortic stiffness and aortic pressure waves, reconstructed from finger blood pressure waves, were obtained in 2490 older adults within the framework of the Rotterdam Study, a large population-based study. Cardiac oxygen supply and demand were estimated using pulse wave analysis techniques, and related to aortic stiffness by linear regression analyses after adjustment for age, sex, mean arterial pressure and heart rate.
Cardiac oxygen demand, estimated as the Systolic Pressure Time Index and the Rate Pressure Product, increased with increasing aortic stiffness [0.27 mmHg s (95% confidence interval: 0.21; 0.34)] and [42.2 mmHg/min (95% confidence interval: 34.1; 50.3)], respectively. Cardiac oxygen supply potential estimated as the Diastolic Pressure Time Index decreased [-0.70 mmHg s (95% confidence interval: -0.86; -0.54)] with aortic stiffening. Accordingly, the supply/demand ratio Diastolic Pressure Time Index/Systolic Pressure Time Index -1.11 (95% confidence interval: -0.14; -0.009) decreased with increasing aortic stiffness.
Aortic stiffness is associated with estimates of increased cardiac oxygen demand and a decreased cardiac oxygen supply potential. These results may offer additional explanation for the relation between aortic stiffness and cardiovascular morbidity and mortality.
Journal of Hypertension 07/2008; 26(6):1237-43. · 4.02 Impact Factor
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ABSTRACT: Mark PS Sie1, Francesco US Mattace-Raso2, André G Uitterlinden2, Pascal P Arp2, Albert Hofman1, Huibert AP Pols2, Arnold PG Hoeks3, Robert S Reneman4, Roland Asmar5, Cornelia M van Duijn1, Jacqueline CM Witteman11Department of Epidemiology and Biostatistics, 2Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; 3Department of Biophysics, 4Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; 5Cardiovascular Institute, Paris, FranceAbstract: Arterial stiffness normally increases with age and has been established as a precursor of cardiovascular disease. Interleukin-6 is a pleiotropic inflammatory cytokine with an important role in the inflammatory cascade, such as up-regulation of C-reactive protein (CRP). The interleukin-6 –174-G/C promoter polymorphism appears to infl uence levels of inflammatory markers, which have been shown to be associated with arterial stiffness. We studied the association of this polymorphism with levels of interleukin-6 and CRP and with arterial stiffness. The study (n = 3849) was embedded in the Rotterdam Study, a prospective, population-based study. Analyses on the association between the –174-G/C polymorphism and pulse wave velocity, distensibility coefficient, and pulse pressure were performed using analyses of variance. Analyses on the levels of inflammatory markers and arterial stiffness were performed using linear regression analyses. Analyses were adjusted for age, sex, mean arterial pressure, heart rate, known cardiovascular risk factors, and atherosclerosis. We found pulse wave velocity to be 0.35 m/s higher for CC-homozygotes vs. wildtype GG-homozygotes (p = 0.018) with evidence for an allele-dose effect (p trend = 0.013), and a similar pattern for pulse pressure (p trend = 0.041). No apparent consistent association with the distensibility coefficient was found. CRP levels were associated with pulse wave velocity (p = 0.007). In conclusion, the interleukin-6 –174 G/C polymorphism is associated with increased arterial stiffness and pulse pressure.Keywords: IL-6, CRP, arterial stiffness, pulse wave velocity, distensibility coefficient, pulse pressure
Vascular Health and Risk Management. 01/2008;
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ABSTRACT: 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.
Journal of Hypertension 06/2007; 25(7):1421-1426. · 4.02 Impact Factor
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ABSTRACT: Objective: To investigate whether arterial stiffening, one of the characteristics of the aging vascular system, is associated with orthostatic hypotension.
Design: Cross-sectional data of a cohort study in elderly men and women.
Participants: We investigated the relationship between arterial stiffness and orthostatic hypotension within the framework of the Rotterdam Study, a population-based study in individuals aged 55 and older. The present study included 3362 subjects participating in the third examination phase. The carotid-femoral pulse wave velocity was used as measure of arterial stiffness. Orthostatic hypotension was assessed with blood pressure measurements in supine and standing position.
Results: Odds ratios for orthostatic hypotension increased through quartiles of pulse wave velocity; the age, gender and mean arterial pressure adjusted odds ratio in the last quartile of pulse wave velocity was 1.45 (95% confidence interval, 1.09-1.93) when compared with the first quartile (reference). In fully adjusted models estimates remained statistically significant. In subjects with higher stiffness we observed a higher drop in blood pressure but no significant change of heart rate.
Conclusions: Arterial stiffness is independently associated with orthostatic hypotension. The drop in blood pressure levels and the contemporary attenuated response of heart rate to orthostatic challenge in subjects with stiffer arteries support the hypothesis that arterial stiffness may explain, at least in part, the reduced baroreflex observed in older adults.
Journal of Hypertension 01/2006; 24(2):339-344. · 4.02 Impact Factor
