Mattace-Raso, F.U.S.

Central but not peripheral fat mass percentage is associated with blood pressure components in the elderly (Article)

2012-07-01T00:00:00Z

the human body composition changes with advances in age. Particularly, the central fat amount increases. Because the central fat mass is a cardiovascular risk factor, we investigated whether in an elderly population, fat mass (measured at different bodily locations) is associated with peripheral and central blood pressure components. cross-sectional design. Using dual-energy X-ray absorptiometry (DEXA), fat mass was measured within a geriatric outpatient clinic population. Blood pressure was measured with an oscillometric device, and aortic blood pressure and augmentation index (AIx) were obtained by radial artery tonometry, using the SphygmoCor system. Multivariate adjustment for confounders was performed using linear regression analyses. totally, 216 subjects were included (age 77.3 years ± 6.1, 34.7% male). The truncal fat mass percentage, but not the peripheral fat mass percentage, was positively associated with the peripheral systolic blood pressure (SBP) [beta 0.07 (95% CI: 0.02 to 0.11)] and the peripheral pulse pressure (PP) [beta 0.07 (95% CI: 0.02 to 0.11)], but negatively with the peripheral diastolic blood pressure (DBP) [beta -0.16 (95% CI -0.27 to -0.04)]. The truncal fat mass percentage was similarly associated with estimated aortic blood pressure components, but no association was found between the truncal fat mass percentage and the AIx. in older persons, the truncal fat mass percentage as a reflection of the central fat mass percentage, but not the peripheral fat mass percentage is associated with peripheral and aortic blood pressure components.

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 variants in novel pathways influence blood pressure and cardiovascular disease risk (Article)

2011-10-06T00:00:00Z

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure (Article)

2011-10-01T00:00:00Z

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10 -8 to P = 2.3 × 10 -13) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

[Cost] effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: Design of a multicenter randomized controlled trial (IMPROveFALL-study) (Article)

2011-08-23T00:00:00Z

Background: Fall incidents represent an increasing public health problem in aging societies worldwide. A major risk factor for falls is the use of fall-risk increasing drugs. The primary aim of the study is to compare the effect of a structured medication assessment including the withdrawal of fall-risk increasing drugs on the number of new falls versus 'care as usual' in older adults presenting at the Emergency Department after a fall. Methods/Design. A prospective, multi-center, randomized controlled trial will be conducted in hospitals in the Netherlands. Persons aged 65 years who visit the Emergency Department due to a fall are invited to participate in this trial. All patients receive a full geriatric assessment at the research outpatient clinic. Patients are randomized between a structured medication assessment including withdrawal of fall-risk increasing drugs and 'care as usual'. A 3-monthly falls calendar is used for assessing the number of falls, fallers and associated injuries over a one-year follow-up period. Measurements will be at three, six, nine, and twelve months and include functional outcome, healthcare consumption, socio-demographic characteristics, and clinical information. After twelve months a second visit to the research outpatient clinic will be performed, and adherence to the new medication regimen in the intervention group will be measured. The primary outcome will be the incidence of new falls. Secondary outcome measurements are possible health effects of medication withdrawal, health-related quality of life (Short Form-12 and EuroQol-5D), costs, and cost-effectiveness of the intervention. Data will be analyzed using an intention-to-treat analysis. Discussion. The successful completion of this trial will provide evidence on the effectiveness of withdrawal of fall-risk increasing drugs in older patients as a method for falls reduction. Trial Registration. The trial is registered in the Netherlands Trial Register (NTR1593).

Measures of body composition and risk of heart failure in the elderly: The Rotterdam study (Article)

2011-05-01T00:00:00Z

Objectives: The incidence of heart failure increases with aging. Aim of the present, study was to determine whether measures body composition predict incident heart failure in older adults. Selling: Prospective community-based cohort study. 5, 868 men and women aged 55 years and older participating the Rotterdam study. Measures of body mass index and waist circumference were obtained at baseline. Information on incident heart failure was obtained during follow-up. Cox regression analyses were performed to investigate the possible association between measure of body composition and incident heart failure. Results: During a mean follow up of 10.9 (SD ±4.4) years, 765 participants had heart failure. After adjustment for age and gender, 1-standard deviation of body mass index, waist circumference and the waist-hip ratio predicted heart failure (HR 1.25; 95% CI 1.17-1.34; HR 1.26; 95% CI 1.18-1.36; and HR 1.17; 95% CI 1.08-1.27), respectively. In age-stratified analyses, 1-standard deviation of body mass index (1.17; 95% CI 1.06-1.29) and waist circumference (1.16; 95% CI 1.05-1.29) were still associated with the risk of heart failure in the oldest participants, whereas the waist-hip ratio was not (1.06; 95% CI 0.945-1.18). Conclusion: Although estimates decrease with age, measures of overall and central adiposity predict incident heart failure among community dwelling older adults.

Arterial stiffness as determinant of increased amino terminal pro-B-type natriuretic peptide levels in individuals with and without cardiovascular disease - The Rotterdam Study (Article)

2010-10-01T00:00:00Z

Objective: Large artery stiffening has adverse effects on cardiac structure and function and, therefore, may be associated with elevated circulating levels of amino-terminal pro-B-type natriuretic peptide (NT-proBNP). Methods: In a large community-dwelling older population (n = 6211, mean age 69.2 years), serum NT-proBNP, brachial pulse pressure (PP) and carotid-femoral pulse wave velocity (cfPWV) were measured. Results: In individuals without cardiovascular disease (CVD), median NT-proBNP was 6.7 pmol/l in men (n = 2073) and 10.1 pmol/l in women (n = 3085) (P < 0.001). In these individuals, indices of arterial stiffness correlated with NT-proBNP with beta-coefficients for brachial PP and cfPWV of 0.315 and 0.255 in men and 0.233 and 0.232 in women (all P < 0.001). After multivariable adjustment (age, weight, height, mean arterial pressure, heart rate, smoking, diabetes, estimated glomerular filtration rate, total and high-density lipoprotein-cholesterol and use of lipid-lowering and antihypertensive medication), these associations remained significant for brachial PP and cfPWV in men and for brachial PP in women. In multivariable-adjusted models, brachial PP explained 20.3% and cfPWV 10.7% of the variation of NT-proBNP in men and, respectively, 10.8 and 9.4% in women. In patients with prevalent CVD, indices of arterial stiffness and NT-proBNP were unrelated in multivariable-adjusted models. Conclusion: Our findings show that arterial stiffness is independently associated with elevated NT-proBNP levels in individuals without prevalent CVD. The association between vascular stiffness and NT-proBNP is stronger in men than in women and absent in individuals with prevalent CVD.

Inflammation and incident-isolated systolic hypertension in older adults: The Rotterdam study (Article)

2010-05-01T00:00:00Z

Objectives: 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. Methods and Results: 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]. Conclusion: 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.

Comparison of Candesartan Versus Metoprolol for Treatment of Systemic Hypertension After Repaired Aortic Coarctation (Article)

2010-01-15T00:00:00Z

Even after successful repair, hypertension is one of the main determinants of cardiovascular morbidity and mortality in patients with aortic coarctation (CoA). We compared the effect of candesartan (angiotensin II receptor blockade) and metoprolol (β-adrenergic receptor blockade) on blood pressure, large artery stiffness, and neurohormonal status in hypertensive patients after repair of CoA. In the present open-label, crossover study, hypertensive patients after CoA repair were first randomly assigned to treatment with candesartan 8 mg or metoprolol 100 mg once per day. After 8 weeks of treatment with one of the drugs, the other treatment was given for 8 weeks. The treatment effects were assessed with 24-hour ambulatory blood pressure monitoring, measurement of large artery stiffness, and neurohormonal plasma levels at baseline and after 8 weeks of either treatment. Sixteen patients (mean age 37 ± 12 years, 26 ± 15 years after repair, 63% men) completed the study. The 24-hour mean arterial pressure at baseline was 97.7 ± 6.2 mm Hg. Metoprolol (mean dose 163 ± 50 mg/day) decreased the mean arterial pressure (7.0 ± 4.2 and 4.1 ± 3.6 mm Hg, respectively) more than did candesartan (mean dose 13 ± 4 mg/day; p = 0.018, 95% confidence interval 0.6 to 5.5). Large artery stiffness did not change with either treatment. With metoprolol, plasma B-type natriuretic peptide increased and plasma renin decreased. With candesartan, the plasma renin and noradrenaline levels increased and aldosterone levels decreased. In conclusion, in adult hypertensive patients after CoA repair, metoprolol had more of an antihypertensive effect than did candesartan. Moreover, the neurohormonal outcome did not support a significant role for the renin-angiotensin system in the causative mechanism of hypertension after CoA.

Genetic variation in the renin-angiotensin system and arterial stiffness. the rotterdam study (Article)

2009-12-04T00:00:00Z

We studied the associations of three renin-angiotensin system polymorphisms, angiotensin-converting enzyme (ACE) ID, angiotensinogen 235 MT, and angiotensin II receptor type I 573 CT, with arterial stiffness. The study was embedded in the Rotterdam Study, a population-based study older adults. The association of the polymorphisms with pulse wave velocity, the carotid distensibility, and pulse pressure was investigated in 3706 subjects. We found no association of the ACE ID polymorphism with pulse wave velocity, but the D-allele was associated with a lower distensibility coefficient (p 0.05) and higher pulse pressure (p 0.01). For the angiotensinogen 235 MT polymorphism, no significant associations with either pulse wave velocity (p 0.71), the distensibility coefficient (p 0.16) or pulse pressure (p 0.34) were found. Also, we found no significant associations of pulse wave velocity (PWV) (p 0.32), the distensibility coefficient (p 0.08), and pulse pressure (p 0.09) with the angiotensin II receptor type 1 573CT polymorphism. No epistatic effects were observed between the three renin-angiotensin system (RAS) genes with arterial stiffness. Our findings suggest that genetic variation in the renin-angiotensin system may play a role in determining carotid distensibility and pulse pressure.

Gender differences in arterial structure and function. Are men really from Mars and women from Venus? (Article)

2009-12-01T00:00:00Z

Gender difference of cardiovascular disease is one of the most investigated and still unsolved items. Finding an answer to this, may have important implications for understanding the differences between men and women in atherosclerosis and possibly lead to the development of gender-specific treatment for cardiovascular disease.

High systolic and pulse pressure levels are associated with better cognitive performance in patients with probable alzheimer's disease: A cross-sectional observational study in a geriatric outpatient population (Article)

2009-11-01T00:00:00Z

Background: The prevalence of cardiovascular disease and Alzheimer's disease (AD) increases with age. A number of studies have demonstrated an association between AD and cardiovascular risk factors and disease. However, data are inconsistent. Methods: Cross-sectional observational study in a geriatric outpatient population. Analysis of data from 327 patients diagnosed with probable AD in a geriatric outpatient clinic. Comparison of blood pressure levels, cardiovascular diagnoses, and Mini-Mental State Examination (MMSE) score between the patients. Results: MMSE score decreased with age (β = -0.25; 95% CI: -0.35 to 0.15), and a positive correlation was found with systolic blood pressure (β = 0.03; 95% CI: 0.003-0.06), pulse pressure (β = 0.05; 95% CI: 0.01-0.08) and hypertension (β = 1.56; 95% CI: 0.05-3.07). An increase in cardiovascular disease load had a negative effect on cognitive performance. After adjustment for duration of dementia (data present for 216 patients), results were slightly changed. Conclusions: Higher systolic blood pressure and pulse pressure were associated with a better cognitive test performance. Patients with probable AD and 2 or more cardiovascular diagnoses had lower MMSE scores. Copyright

Biomarkers of left atrial volume: A longitudinal study in patients with end stage renal disease (Article)

2009-10-01T00:00:00Z

Left atrial volume (LAV) has recently emerged as a useful biomarker for risk stratification and risk monitoring in patients with end stage renal disease. We investigated the relationship between cardiac natriuretic peptides (atrial natriuretic peptide [ANP] and brain natriuretic peptide [BNP]) and norepinephrine (NE) with LAV and LAV changes over time in 199 end stage renal disease patients. At baseline, LAV was directly related to BNP (r=0.60), ANP (r=0.59), and NE (r=0.28; P<0.001), and these relationships held true in multiple-regression models adjusting for potential confounders (P≤0.003). In the longitudinal study (17±2 months), LAV increased from 9.8±4.6 to 10.9±5.4 mL/m (+11%). In a multiple linear regression model, BNP (β=0.28; P=0.003), ANP (β=0.22; P=0.03), and NE (β=0.27; P=0.003) predicted LAV changes. The area under the receiver operating characteristic curve for predicting LAV changes (>3 mL/m per year) of a risk score on the basis of standard risk factors was 0.72. Plasma BNP (+12%; P=0.004), ANP (+8%; P=0.03), NE (+8%; P=0.05) and midwall fraction shortening (+8%; P=0.05) increased the area under the receiver operating characteristic curve to a significant extent, whereas LV mass did not (+5%; P=0.18). Predictive models, including BNP, ANP, and NE, maintained a satisfactory discriminatory power for LAV and LAV changes also when tested by a bootstrap resampling technique. BNP and ANP are strongly related to LAV in the end stage renal disease patients and predict LAV changes over time in these patients. Because an increased LAV underlies diastolic dysfunction and/or volume overload (ie, potentially modifiable risk factors), the measurement of the plasma concentration of these compounds might be useful for risk stratification and for guiding treatment in dialysis patients.

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.

Large artery stiffness and microalbuminuria: A causal relationship? (Article)

2009-07-01T00:00:00Z

Orthostatic hypotension in older persons: A diagnostic algorithm (Article)

2009-06-01T00:00:00Z

Orthostatic hypotension (OH) is a frequent phenomenon in older persons and usually has a multifactorial origin. When the diagnosis is suspected, the work-up should initially be directed at the most prevalent causes. This clinical algorithm may be a useful tool in the diagnostic process. The Journal of Nutrition, Health & Aging

Genome-wide association study of blood pressure and hypertension (Article)

2009-06-01T00:00:00Z

Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P 4 × 10 7. The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P 5 × 10 8) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.

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.

Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease (Article)

2008-07-01T00:00:00Z

Background/Aims: Recent studies suggest that vitamin D metabolites may be important for preserving cognitive function via specific neuroprotective effects. No large studies have examined the association between vitamin D status and cognition. Methods: In this cross-sectional study, we analyzed the serum 25-hydroxyvitamin D3levels and Mini-Mental State Examination (MMSE) test scores of 225 older outpatients who were diagnosed as having probable Alzheimer's disease (AD). In addition to the 25-hydroxyvitamin D3levels, we analyzed the serum vitamin B1, B6and B12levels. Results: An association was found between MMSE test scores and serum 25-hydroxyvitamin D3levels, with a β-coefficient of 0.05 (p = 0.01). Vitamin-D-sufficient patients had significantly higher MMSE scores as compared to vitamin-D-insufficient ones. No association was found with the other serum vitamin levels. Conclusions: These data support the idea that a relationship exists between vitamin D status and cognition in patients with probable AD. However, given the cross-sectional design of this study, no causality can be concluded. Further prospective studies are needed to specify the contribution of vitamin D status to the onset and course of cognitive decline and AD. Copyright

Age and blood pressure levels modify the functional properties of central but not peripheral arteries (Article)

2008-06-01T00:00:00Z

The effect of age and blood pressure on the carotid and the radial artery distensibilities was investigated. Patients referred to the outpatient clinic of the Department of Internal Medicine and Geriatric Medicine were asked to participate in the study. The carotid and radial artery distensibility coefficients were measured. Linear regression analyses were performed to investigate the associations between determinants and arterial distensibility. The mean age of the participants was 72.3 years, and 41.5% were men. Carotid distensibility decreased with age in adjusted models (β = -0.317; 95% confidence interval [CI], -0.241, -0.055), whereas the radial distensibility did not decrease. Levels of systolic blood pressure and mean arterial pressure were associated with decreasing levels of carotid distensibility, whereas the diastolic blood pressure and pulse pressure were not associated (β = -0.571; 95% CI, -0.404, -0.007; β = -0.410; 95% CI, -0.308, -0.101, respectively). In conclusion, age and blood pressure levels are associated with the distensibility of the central arteries but not with that of the peripheral arteries.

Aortic stiffness and the balance between cardiac oxygen supply and demand: The Rotterdam Study (Article)

2008-06-01T00:00:00Z

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The association of arterial stiffness and arterial calcification: The Rotterdam Study (Article)

2008-03-01T00:00:00Z

The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine predicts renal prognosis in IgA nephropathy (Article)

2008-02-01T00:00:00Z

The production of cytokines by resident and non-resident renal cells during immunoglobulin A nephropathy (IgAN) plays a key role in the progression of renal damage. The aim of this study was to determine if measurements of urinary epidermal growth factor (EGF) and monocyte chemotactic peptide-1 (MCP-1), at the time of renal biopsy, were a predictor of end-stage renal disease (ESRD) in a cohort of 132 patients with biopsy-proven IgAN. Outcome measures were a doubling of the baseline serum creatinine (sCr) and/or ESRD. Patients with ratios of EGF/MCP-1 in the lowest tertile had a significant decline in renal survival, while patients in the highest tertile maintained 100% renal survival at 48 and 84 months of follow-up. Multivariate Cox's regression analysis showed that the urine EGF/MCP-1 ratio was an independent prognostic factor and indirectly correlated with the combined outcome. The predictive value was also measured by the area under the receiver operating characteristic curve (ROC). The area of the EGF/MCP-1 ratio was significantly higher than that of EGF or MCP-1 alone, histologic grade, creatinine clearance, or proteinuria. Our study suggests that the urinary EGF/MCP-1 ratio may be used as a prognostic marker of ESRD for patients with IgAN.

Insertion/deletion gene polymorphism of the angiotensin-converting enzyme and blood pressure changes in older adults. The Rotterdam study (Article)

2007-09-01T00:00:00Z

The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene may be involved in determining blood pressure changes. The aim of the present study was to assess the relationship between the ACE I/D gene and the change of blood pressure levels during follow-up. We calculated the difference between mean levels of SBP, DBP and PP obtained during the two observations as follows: BP mean levels obtained at third phase minus the BP mean levels at baseline and subsequently we investigated the association of the ACE I/D polymorphism and the mean changes of SBP, DBP and PP levels. The study was conducted within the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. Information on the II, ID and DD genotypes of the ACE gene and mean change of blood pressure levels were available in 3966 subjects. In adjusted models, subjects with the D allele had higher mean changes of systolic and pulse pressure (PP) than subjects with the I allele. The mean changes of systolic blood pressure were 6.1 (4.7-7.5), 8.2 (7.5-9.3) and 7.4 (5.9-8.5) mm Hg in subjects with the II, ID and DD genotype, respectively. The corresponding mean changes of PP through genotypes were 4.3 (3.3-5.4), 6.0 (5.3-6.7) and 5.9 (4.9-6.9) mm Hg, respectively. No difference was found for mean change of diastolic blood pressure among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with increased mean changes of systolic and PP.

Remitting seronegative symmetrical synovitis with pitting oedema associated with lung malignancy (Article)

2007-07-01T00:00:00Z

RS3PE syndrome is an inflammatory disease which affects mainly males and responds rapidly to low-dose steroids. We describe the concurrence of RS3PE and lung malignancy in a 78-year-old woman. We recommend that an underlying malignancy should always be excluded in patients with RS3PE syndrome, even when general signs and symptoms such as weight loss, anorexia and fever are absent or uncertain.

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.

Arterial stiffness, cognitive decline, and risk of dementia: the Rotterdam study (Article)

2007-03-01T00:00:00Z

BACKGROUND AND PURPOSE: Arterial stiffness is associated with an increased risk of myocardial infarction and stroke, independent of classical vascular risk factors. Vascular factors and stroke are associated with cognitive function and dementia. We examined whether arterial stiffness was independently associated with cognitive function and dementia. METHODS: The present study was based on the Rotterdam Study, a prospective population-based cohort study ongoing since 1990. During the third examination (1997-1999) arterial stiffness was measured by assessment of pulse wave velocity and carotid distensibility. Cognitive function was assessed during the third and fourth examination (2002-2004) with a neuropsychological test battery. We used linear and logistic regression to estimate the association of arterial stiffness with cognitive function and cognitive decline. From the third examination until January 1, 2005, we identified 156 incident dementia cases. Cox proportional hazard models were used to estimate the association between arterial stiffness and the risk of dementia. RESULTS: After adjustment for cardiovascular risk factors we found an association of increased pulse wave velocity with poorer performance on the Stroop test (adjusted beta-coefficient [95% confidence interval] 1.13 [0.26 to 1.99] per standard deviation increase in pulse wave velocity) but not with performance on other cognitive tests. No associations were found between measures of arterial stiffness and cognitive decline or risk of dementia after adjustment for cardiovascular factors. CONCLUSIONS: We did not identify arterial stiffness as an independent risk factor of cognitive decline or risk of dementia.