Showing papers by "Robert Fagard published in 2008"

Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials.

Abstract: Objective To quantify the relative risk reductions achieved with different regimens to lower blood pressure in younger and older adults. Design Meta-analyses and meta-regression analyses used to compare the effects on the primary outcome between two age groups ( or =65 years). Evidence for an interaction between age and the effects of treatment sought by fitting age as a continuous variable and estimating overall effects across trials. Primary outcome total major cardiovascular events. Results 31 trials, with 190 606 participants, were included. The meta-analyses showed no clear difference between age groups in the effects of lowering blood pressure or any difference between the effects of the drug classes on major cardiovascular events (all P> or =0.24). Neither was there any significant interaction between age and treatment when age was fitted as a continuous variable (all P>0.09). The meta-regressions also showed no difference in effects between the two age groups for the outcome of major cardiovascular events ( or =65; P=0.38). Conclusions Reduction of blood pressure produces benefits in younger ( or =65 years) adults, with no strong evidence that protection against major vascular events afforded by different drug classes varies substantially with age.

Daytime and Nighttime Blood Pressure as Predictors of Death and Cause-Specific Cardiovascular Events in Hypertension

Abstract: Our aim was to assess the prognostic significance of nighttime and daytime ambulatory blood pressure and their ratio for mortality and cause-specific cardiovascular events in hypertensive patients without major cardiovascular disease at baseline. We performed a meta-analysis on individual data of 3468 patients from 4 prospective studies performed in Europe. Age of the subjects averaged 61+/-13 years, 45% were men, 13.7% smoked, 8.4% had diabetes, and 61% were under antihypertensive treatment at the time of ambulatory blood pressure monitoring. Office, daytime, and nighttime blood pressure averaged 159+/-20/91+/-12, 143+/-17/87+/-12, and 130+/-18/75+/-12 mm Hg. Total follow-up amounted to 23 164 patient-years. We used multivariable Cox regression analysis to assess the hazard ratios associated with 1 standard deviation higher blood pressure. Daytime and nighttime systolic blood pressure predicted all-cause and cardiovascular mortality, coronary heart disease, and stroke, independently from office blood pressure and confounding variables. When these blood pressures were entered simultaneously into the models, nighttime blood pressure predicted all outcomes, whereas daytime blood pressure did not add prognostic precision to nighttime pressure. Appropriate interaction terms indicated that the results were similar in men and women, in younger and older patients, and in treated and untreated patients The systolic night-day blood pressure ratio predicted all outcomes, which only persisted for all-cause mortality after adjustment for 24-hour blood pressure. In conclusion, nighttime blood pressure is in general a better predictor of outcome than daytime pressure in hypertensive patients, and the night-day blood pressure ratio predicts mortality, even after adjustment for 24-hour blood pressure.

Daytime and Nighttime Blood Pressure as Predictors of Death and Cause-Specific Cardiovascular Events in Hypertension. Commentary

Abstract: -Our aim was to assess the prognostic significance of nighttime and daytime ambulatory blood pressure and their ratio for mortality and cause-specific cardiovascular events in hypertensive patients without major cardiovascular disease at baseline. We performed a meta-analysis on individual data of 3468 patients from 4 prospective studies performed in Europe. Age of the subjects averaged 61±13 years, 45% were men, 13.7% smoked, 8.4% had diabetes, and 61% were under antihypertensive treatment at the time of ambulatory blood pressure monitoring. Office, daytime, and nighttime blood pressure averaged 159±20/91±12, 143±17/87±12, and 130±18/75±12 mm Hg. Total follow-up amounted to 23 164 patient-years. We used multivariable Cox regression analysis to assess the hazard ratios associated with 1 standard deviation higher blood pressure. Daytime and nighttime systolic blood pressure predicted all-cause and cardiovascular mortality, coronary heart disease, and stroke, independently from office blood pressure and confounding variables. When these blood pressures were entered simultaneously into the models, nighttime blood pressure predicted all outcomes, whereas daytime blood pressure did not add prognostic precision to nighttime pressure. Appropriate interaction terms indicated that the results were similar in men and women, in younger and older patients, and in treated and untreated patients The systolic night-day blood pressure ratio predicted all outcomes, which only persisted for all-cause mortality after adjustment for 24-hour blood pressure. In conclusion, nighttime blood pressure is in general a better predictor of outcome than daytime pressure in hypertensive patients, and the night-day blood pressure ratio predicts mortality, even after adjustment for 24-hour blood pressure.

Left ventricular strain and strain rate in a general population.

Abstract: Aims Strain and strain rate (SR) are measures of deformation that reflect left ventricular (LV) function. To our knowledge, no previous study described these indexes in a general population. We therefore described peak-systolic strain and SR of the LV in the general population and derived diagnostic thresholds for these measurements in a healthy subgroup. Methods and results In 480 subjects enrolled in a family-based population study (50.5% women; mean age, 50.5 years; 37.2% hypertensive), we measured: (i) end-systolic longitudinal strain and peak-systolic SR from the basal portion of the LV inferior and inferolateral free walls; (ii) radial deformation of the LV inferolateral wall. Longitudinal (mean, 22.9%) and radial (59.2%) strain and longitudinal (1.31 s−1) and radial (3.40 s−1) SR decreased with age ( P ≤ 0.007). Longitudinal and radial strain independently decreased ( P ≤ 0.006) with relative wall thickness (RWT), longitudinal strain with the waist-to-hip ratio, and radial strain with body weight. In contrast, LV ejection fraction increased ( P ≤ 0.0001) with age and RWT. Longitudinal and radial stain rate increased with heart rate ( P ≤ 0.05). In healthy subgroup ( n = 236), the fifth percentiles were 18.4 and 44.3%, and 0.99 and 2.43 s−1, for longitudinal and radial strain and SR, respectively. Conclusion We explored the early signs of LV systolic dysfunction in a general population, using tissue Doppler imaging technique. LV strain and SR decrease with age, body weight, central obesity, and RWT. Our current study resulted in the proposal for diagnostic thresholds for strain and SR, based on a healthy subgroup recruited via random sampling of the population.

Prognostic significance of ambulatory blood pressure in hypertensive patients with history of cardiovascular disease.

Abstract: Objective To assess the prognostic significance of nighttime and daytime blood pressure (BP), their ratio and the nighttime dipping pattern for mortality and recurrent cardiovascular (CV) events in patients with CV disease at baseline. Background The prognostic value of ambulatory BP has not been reported in hypertensive patients with a history of CV disease.

Short-term and long-term repeatability of the morning blood pressure in older patients with isolated systolic hypertension.

Abstract: Objective Using 24-h ambulatory blood pressure monitoring, we studied the repeatability of the morning blood pressure in older (>= 60 years) patients with isolated systolic hypertension. Methods The sleep-through morning surge was the morning blood pressure minus the lowest nighttime blood pressure. The preawake morning surge was the morning blood pressure minus the preawake blood pressure. In addition, we determined the cusum plot height of blood pressure from 04: 00 to 10: 00 h from a plot of cumulative sums. Results In 173 patients with repeat recordings within 33 days (median), the short-term repeatability coefficients, expressed as percentages of maximal variation, ranged from 35 to 41% for the daytime and nighttime blood pressures and from 50 to 56% for the night-to-day blood pressure ratios. Short-term repeatability ranged from 52 to 75% for the sleep-through and the preawake morning surge, and from 51 to 62% for the cusum plot height. In 219 patients with repeat recordings within 10 months (median), the corresponding long-term estimates ranged from 45 to 64%, from 69 to 71%, from 76 to 83%, and from 50 to 78%, respectively. In categorical analyses of the short-term repeatability of the sleep-through morning surge and the preawake morning surge, using the 75th percentile as arbitrary cut-off, surging status changed in 28.0 and 26.8% of patients (k-statistic <= 0.33). In the long-term interval, these proportions were 32.0 and 32.0%, respectively (k-statistic <= 0.20). The k-statistic threshold for moderate reproducibility is 0.4. Conclusion The morning surge of blood pressure is poorly reproducible, irrespective of whether it is analysed as continuous or categorical variable.

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins.

Abstract: Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

Heritability and intrafamilial aggregation of arterial characteristics.

Abstract: BackgroundWe investigated the heritability and familial aggregation of various indexes of arterial stiffness and wave reflection and we partitioned the phenotypic correlation between these traits into shared genetic and environmental components.MethodsUsing a family-based population sample, we recru

Effects of genetic variation in adducin on left ventricular diastolic function as assessed by tissue Doppler imaging in a Flemish population.

Abstract: BACKGROUND We investigated the possible association between left ventricular diastolic function and the ADD1 Gly460Trp and ADD3 IVS11 +386A>G polymorphisms alone and in combination. METHODS In a family-based population study (473 subjects; 50.5% women; mean age 50.5 years), we measured early (Ea) and late (Aa) diastolic peak velocities of the mitral annulus by tissue Doppler imaging. In multivariate-adjusted analyses, we investigated phenotype-genotype associations, while accounting for confounders and family structure. RESULTS Lateral Ea/Aa ratio was higher in ADD1 Trp allele carriers than in GlyGly homozygotes (1.51 vs. 1.40; P = 0.005) and was lower in ADD3 A allele carriers than in GG homozygotes (1.42 vs. 1.55; P = 0.005). The effects of ADD1 on the lateral Ea and Ea/Aa weakened with older age (P 0.20). Transmission of the ADD1 Trp allele to offspring was associated with higher lateral Ea (+0.91; P = 0.026) and Ea/Aa ratio (+0.23; P = 0.0008). CONCLUSION Our population-based study demonstrated that left ventricular diastolic relaxation is modulated by genetic variation in ADD1 and ADD3. This association was more prominent in younger subjects in whom longstanding environmental factors and ageing are less likely to mask genetic effects.

Treatment of elderly hypertensive patients with epithelial sodium channel inhibitors combined with a thiazide diuretic reduces coronary mortality and sudden cardiac death.

Abstract: No reduction in either coronary mortality or sudden cardiac death (SCD) has been demonstrated in overviews of randomized trials of treatment of hypertension with diuretics. An overview was conducted of coronary mortality and SCD in randomized controlled antihypertensive trials in which an epithelial sodium channel (ENaC) inhibitor/hydrochlorothiazide (HCTZ) combination was used. Secondarily, an analogous overview in which thiazide diuretic was used alone was performed. Randomized trials that used an ENaC inhibitor/HCTZ combination (or, alternatively, thiazide diuretic alone) were identified from previous meta-analyses, searches of PubMed, search of the Cochrane Clinical Trials database, and review of publications that addressed the consequences of treating hypertension. Trials in which participants were randomized to either an ENaC inhibitor combined with a thiazide diuretic (or to a thiazide diuretic alone) or to control treatment for at least 1 year and in which coronary mortality was reported were included. Numbers of events in individual trials were abstracted independently by two authors. Significant reductions in both coronary mortality and SCD were observed in the overview of trials in which elderly patients received an ENaC inhibitor/HCTZ combination. The odds ratio (OR) for coronary mortality was 0.59 (95% confidence interval [CI], 0.44 to 0.78) and for SCD was 0.60 (95% CI, 0.38 to 0.94). In contrast, an overview of the trials using thiazide diuretics alone showed no significant reductions of either coronary mortality (OR, 0.94; 95% CI, 0.81 to 1.09) or SCD (OR, 1.27; 95% CI, 0.93 to 1.75). Use of an ENaC inhibitor combined with HCTZ for treatment of hypertension in the elderly results in favorable effects on coronary mortality and SCD.

Anthropometry, carbohydrate and lipid metabolism in the East Flanders Prospective Twin Survey: linkage of candidate genes using two sib-pair based variance components analyses.

Abstract: Insulin resistance and obesity are underlying causes of type 2 diabetes and therefore much interest is focused on the potential genes involved. A series of anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ twin pairs recruited from the East Flanders Prospective Twin Survey. Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR, LEP, LEPR, PPARgamma and the RETN gene were genotyped. Univariate single point variance components linkage analyses were performed using two methods: (1) the standard method, only comprising the phenotypic and genotypic data of the DZ twin pairs and (2) the extended method, also incorporating the phenotypic data of the MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8 marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP marker showed suggestive linkage with birth weight. This study suggests that DNA variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2 diabetes. In addition, the two methods used to perform linkage analyses yielded similar results. This was however not the case for birth weight where chorionicity seems to be an important confounder.

Cardiovascular control in space and on earth: The challenge of gravity

Abstract: A total of five studies have been included in this work. The first two studies describe cardiovascular response changes to (simulated) microgravity in healthy subjects. In a third study, the circulatory response to standing is discussed in five cosmonauts before and after short-duration spaceflight. The last two studies deal with failing adaptive mechanisms of orthostatic blood-pressure control in patients who are prone to head-up tilt induced syncope. The team of Professor A. E. Aubert (F. Beckers, K. Couckuyt and J. Liu) from the Laboratory of Experimental Cardiology of the University Hospital in Leuven was involved in the completion of this thesis. Part of the work has been coordinated by Dr. W. Wieling (J. Gisolf and J.M. Karemaker) of the Academic Medical Center in Amsterdam and by Professor H. Ector (T. Reybrouck) of the Division of Clinical Cardiology in Leuven.

Is the predictive power of a low-pulse pressure independent of peak oxygen uptake in advanced chronic heart failure?

Abstract: A pulse pressure (PP) below 35-40 mm Hg has been shown to carry a worse prognosis in patients with chronic heart failure (CHF), but its non-dependence on peak oxygen uptake, which is a major if not the major prognostic factor in these patients, has not been studied. We assessed whether PP adds prognostic precision to peak oxygen uptake in 284 patients with advanced CHF, in whom blood pressure (BP) was measured at rest and who performed a graded symptom-limited bicycle exercise test with respiratory gas analysis. The results confirm that a low PP rather than a high PP predicts cardiovascular (CV) mortality in patients with CHF and that PP adds prognostic value to peak oxygen uptake, which is the strongest predictor of outcome.

Influencing the natural history of hypertension: it is the blood pressure achieved more than the drug.

Abstract: In his editorial ‘Influencing the natural history of hypertension: Is it the blood pressure achieved, the drug or the drug dose?’ [1] Dr Hollenberg addresses questions that have been debated among hypertensiologists for quite some time. Although there is no clearly stated conclusion, Dr Hollenberg appears to believe that the drug and drug dose do matter, particularly with regard to drugs that interfere with the renin–angiotensin system.