Showing papers by "Robert Fagard published in 2009"

Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document.

Abstract: Abbreviations ACE: angiotensin-converting enzyme; BP: blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; ET: endothelin; IMT: carotid intima-media thickness; JNC: Joint National Commit

Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study

Abstract: BackgroundHypertension guidelines advise aggressive blood pressure (BP) lowering in patients with diabetes or high cardiovascular risk, but supporting evidence is limited We analysed the impact of BP on cardiovascular events in well treated high-risk patients enrolled in a large clinical trial (Ong

Prevalence of Left Ventricular Diastolic Dysfunction in a General Population

Abstract: Background—Because the process of myocardial remodelling starts before the onset of symptoms, recent heart failure (HF) guidelines place special emphasis on the detection of subclinical left ventricular (LV) systolic and diastolic dysfunction and the timely identification of risk factors for HF. Our goal was to describe the prevalence and determinants (risk factors) of LV diastolic dysfunction in a general population and to compare the amino terminal probrain natriuretic peptide level across groups with and without diastolic dysfunction. Methods and Results—In a randomly recruited population sample (n539; 50.5% women; mean age, 52.5 years), we measured early and late diastolic peak velocities of mitral inflow (E and A), pulmonary vein flow by pulsed-wave Doppler, and the mitral annular velocities (Ea and Aa) at 4 sites by tissue Doppler imaging. A healthy subsample of 239 subjects (mean age, 43.7 years) provided age-specific cutoff limits for normal E/A and E/Ea ratios and the differences in duration between the mitral A and the reverse pulmonary vein flows during atrial systole (AdARd). The number of subjects in diastolic dysfunction groups 1 (impaired relaxation), 2 (elevated LV end-diastolic filling pressure), and 3 (elevated E/Ea and abnormally low E/A) were 53 (9.8%), 76 (14.1%), and 18 (3.4%), respectively. We used (AdARd10) to confirm possible elevation of LV filling pressures in group 2. Compared with subjects with normal diastolic function (n392, 72.7%), group 1 (209 versus 251 pmol/L; P0.015) and group 2 (209 versus 275 pmol/L; P0.0003) but not group 3 (209 versus 224 pmol/L; P0.65) had a significantly higher adjusted NT-probrain natriuretic peptide. Higher age, body mass index, heart rate, systolic blood pressure, serum insulin, and creatinine were significantly associated with a higher risk of LV diastolic dysfunction. Conclusions—The overall prevalence of LV diastolic dysfunction in a random sample of a general population, as estimated from echocardiographic measurements, was as high as 27.3%. (Circ Heart Fail. 2009;2:105-112.)

Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension.

Abstract: Our objective was to assess the prognostic significance of the night-time dipping pattern and the night–day blood pressure (BP) ratio for mortality and cardiovascular events in hypertensive patients without major cardiovascular disease at baseline. We performed a meta-analysis on individual data of 3468 patients from four prospective studies performed in Europe. Age of the subjects averaged 61±13 years; 45% were men and 61% were under antihypertensive treatment at the time of ambulatory BP monitoring. The night–day BP ratio and 24-h BP averaged, respectively, 0.907±0.085/0.866±0.095 and 138.1±16.4/82.3±11.0 mm Hg. Total follow-up time amounted to 23 164 patient-years. We used multivariable Cox regression analysis to assess the outcome of reverse dippers, non-dippers and extreme dippers vs dippers, and to assess the hazard ratios associated with 1 standard deviation higher night–day BP ratio. In comparison with dippers, and with adjustment for confounders and 24-h BP, the incidence of cardiovascular events was worse in reverse dippers (P⩽0.05), whereas mortality was lower in extreme dippers (P⩽0.01); outcome was similar in non-dippers and dippers. The systolic night–day BP ratio independently predicted all-cause mortality and cardiovascular events (P⩽0.001), which persisted after additional adjustment for 24-h BP (P⩽0.05); appropriate interaction terms indicated that the results were similar in men and women, in younger and older patients and in treated and untreated patients. In conclusion, the dipping pattern and the night–day BP ratio significantly and independently predict mortality and cardiovascular events in hypertensive patients without history of major cardiovascular disease, even after adjustment for 24-h BP.

Regression of Left Ventricular Mass by Antihypertensive Treatment A Meta-Analysis of Randomized Comparative Studies

Abstract: Blood pressure–lowering therapy reduces left ventricular mass, but the question of whether differences exist among drug classes has not been fully resolved. Our aim was to compare the effects of diuretics, β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers on left ventricular mass regression in patients with hypertension on the basis of prospective, randomized comparative studies. We performed meta-analyses, involving pooled pairwise comparisons of the drug classes and of each class versus other classes statistically combined, and meta-regression analyses to identify the determinants of the regression. The 75 relevant publications involved 84 pairwise comparisons and 6001 patients. Regression of left ventricular mass was significantly less ( P =0.01) with β-blockers (9.8%) than with angiotensin receptor blockers (12.5%), but none of the other analyzable pairwise comparisons between drug classes revealed significant differences ( P >0.10). In addition, β-blockers showed less regression than the other 4 classes statistically combined ( P P P

Effects of Telmisartan, Ramipril, and Their Combination on Left Ventricular Hypertrophy in Individuals at High Vascular Risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease

Abstract: Background— Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers reduce left ventricular hypertrophy (LVH). The effect of these drugs on LVH in high-risk patients without heart failure is unknown. Methods and Results— In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), patients at high vascular risk and tolerant of ACE inhibitors were randomly assigned to ramipril, telmisartan, or their combination (n=23 165). In the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND), patients intolerant of ACE inhibitors were randomized to telmisartan or placebo (n=5343). Prevalence of LVH at entry in TRANSCEND was 12.7%. It was reduced by telmisartan (10.5% and 9.9% after 2 and 5 years) compared with placebo (12.7% and 12.8% after 2 and 5 years) (overall odds ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.0017). New-onset LVH occurred less frequently with telmisartan compared...

Dipping pattern of nocturnal blood pressure in patients with hypertension

Abstract: Four dipping categories have been described, based on the night-day blood pressure ratio from 24-h ambulatory blood pressure recordings: extreme dippers (night-day blood pressure ratio 1.0). The main purpose of this article is to discuss the prognostic significance of these four dipping categories in hypertension, mainly based on a large meta-analysis of individual patient data. In hypertensive patients without cardiovascular disease at baseline and with statistical adjustment for confounders and 24-h blood pressure, mortality was lower in extreme dippers than in dippers, whereas the incidence of cardiovascular events was higher in reverse dippers. The worst prognosis for reverse dippers was also observed in hypertensive patients with major cardiovascular disease at baseline. Higher incidences of cardiovascular events and mortality were also found in reverse dippers in comparison with dippers in a comprehensive meta-analysis of population-based studies but outcome was not significantly different between extreme dippers and dippers. Based on these findings, there appears to be little doubt that reverse dipping is associated with a worse prognosis. Some studies suggest that prognosis is similar in nondippers and extreme dippers in comparison with dippers, but other studies suggest a somewhat worse prognosis in nondippers, or a better or worse prognosis in extreme dippers.

Smoking Amplifies Cardiovascular Risk in Patients With Hypertension and Diabetes

Abstract: Smoking is considered an important “risk factor” for arterial hypertension and diabetes management, according to, respectively, the current guidelines of the European Society of Hypertension and the European Society of Cardiology on the management of arterial hypertension (1) and the guidelines on diabetes of the European Society of Cardiology and the European Association for the Study of Diabetes (2). The aim of the current article is to further evaluate the effect of smoking on mortality and cause-specific cardiovascular events in hypertension and in diabetes and to assess whether there is a significant interaction between the effects of smoking and diabetes. To assess the effect of smoking on mortality and cause-specific cardiovascular events, and the interaction between smoking and diabetes, we analyzed a database of 3,468 hypertensive patients without major cardiovascular disease at baseline and with prospective follow-up for morbidity and mortality (3). The database consists of individual data of hypertensive patients from four prospective studies performed in Europe (4–7). Age of the subjects averaged 61 ± 13 years (mean ± SD), 45% were men, and 61% were under antihypertensive treatment at baseline. Office blood pressure averaged 159.0 ± 19.9/91.0 ± 11.7 mmHg and 24-h ambulatory blood pressure 138.1 ± 16.4/82.3 ± 11.0 mmHg. Current smoking and diabetes were coded as yes or no at the baseline examination; 13.7% of the patients smoked and 8.4% had diabetes. We used Cox proportional hazards regression analysis to assess the prognostic significance of smoking, with stratification for study and adjustment for age, sex, diabetes, total cholesterol, 24-h systolic blood pressure, antihypertensive treatment, and BMI. The average 24-h blood pressure was used because its predictive power has been shown to be superior to that of office blood pressure (3). Median follow-up time was 6.57 years (range 0.08–13.1) and total follow-up time amounted to …

Cardiovascular and biochemical risk factors for incident dementia in the Hypertension in the Very Elderly Trial.

Abstract: OBJECTIVES: Several cardiovascular and biochemical factors including hypertension have been associated with cognitive decline and dementia, although both epidemiological and intervention evidence is mixed with the majority of studies examining those in midlife or younger elderly and the recent Hypertension in the Very Elderly Trial showing no significant association between blood pressure lowering and incident dementia. It has also been suggested that risk factors may differ in the very elderly. The aim of these analyses was to examine the impact of baseline cardiovascular and biochemical factors upon incident dementia and cognitive decline in a very elderly hypertensive group. METHODS: Participants of the Hypertension in the Very Elderly Trial were aged at least 80 years and hypertensive. Cognitive function was assessed at baseline and annually with diagnostic information collected for dementia and relationships between baseline total and high-density lipoprotein cholesterol, creatinine, glucose, haemoglobin, heart failure, atrial fibrillation, diabetes, previous stroke and later dementia/cognitive decline were examined. RESULTS: There were 3336 participants with longitudinal cognitive function data. In multivariate analyses higher creatinine was associated with a lower risk of incident dementia and cognitive decline. Higher total and lower high-density lipoprotein cholesterol were associated with lower risk of cognitive decline. Other variables were not significant. CONCLUSIONS: In very elderly hypertensive patients heart failure, diabetes, atrial fibrillation, prior stroke, glucose and haemoglobin levels did not demonstrate a relationship with cognitive decline or dementia. Higher creatinine (excluding moderate renal impairment) was associated with a lower risk of dementia and cognitive decline. The findings for total and high-density lipoprotein cholesterol add to the varied literature in this area and together these findings may add weight to the suggestion that risk factor profiles differ in the very elderly.

Independent Relations of Left Ventricular Structure With the 24-Hour Urinary Excretion of Sodium and Aldosterone

Abstract: Previous studies reported on the association of left ventricular mass index (LVMI) with urinary sodium or with circulating or urinary aldosterone. We investigated the independent associations of LV...

Smoking as an independent risk factor for myocardial infarction or stroke in type 2 diabetes : a report from the Swedish National Diabetes Register

Abstract: BACKGROUND: Few earlier studies have analysed smoking as a risk factor for myocardial infarction (MI) or stroke in type 2 diabetic patients. DESIGN AND METHODS: A longitudinal study involved 13 087 female and male patients with type 2 diabetes from the Swedish National Diabetes Register with no previous MI or stroke at baseline, aged 30-74 years, and with data available for all analysed variables, followed up for mean 5.7 years. RESULTS: Adjusted hazard ratios (HRs) for smoking and first-incident fatal/nonfatal MI, stroke and total mortality were 1.7 [95% confidence interval (CI): 1.4-2.0; P<0.001], 1.3 (95% CI: 1.1-1.6; P = 0.006) and 1.8 (95% CI: 1.5-2.2; P<0.001), respectively, by Cox regression analysis, adjusted for age, sex, diabetes duration, hypoglycaemic treatment, haemoglobin A1c, blood pressure, body mass index, microalbuminuria, antihypertensive and lipid-lowering drugs. Adjusted HR was higher for fatal MI, 2.1 (95% CI: 1.7-2.7; P<0.001), than for nonfatal MI, 1.4 (95% CI: 1.2-1.7; P<0.001). The highest HRs were observed in more frequently smoking (22%), middle-aged patients (age <60 years) for fatal/nonfatal MI, 2.3 (95% CI: 1.8-3.1; P<0.001) and for total mortality, 2.5 (95% CI: 1.6-3.8, P<0.001), whereas lower HRs were observed in older and less smoking patients. With predicted cessation of smoking in patients aged below 60 years, 24% (95% CI: 15-33%) of cases of fatal/nonfatal MI and 24% (11-37%) of cases of total mortality may have been prevented. CONCLUSION: The risk for MI and total mortality associated with smoking is high in type 2 diabetes, especially in more frequently smoking, middle-aged patients, and was higher for MI than for stroke, and also higher for fatal than for nonfatal events. Smoking cessation would strongly affect risk reduction.

Left ventricular geometry and endogenous ouabain in a Flemish population.

Abstract: Background Endogenous ouabain, an endogenous digitalis-like steroid, is synthesized in the adrenal glands and possibly in the hypothalamus. In vitro and in vivo, endogenous ouabain triggers growth and proliferation of cardiomyocytes. Objective We therefore investigated the association between left ventricular structure and function and plasma endogenous ouabain in a general population. Methods We randomly recruited 536 individuals from a general population (50.7% women, mean age 53.1 years). Measurements included echocardiographic left ventricular structure and function, blood pressure, plasma endogenous ouabain, and the 24-h urinary excretion of sodium. Results The geometric mean plasma endogenous ouabain was 95.5 pmol/l (interquartile range 79.4-120.2 pmol/l). We expressed effect sizes for a 1-SD increase in plasma endogenous ouabain (0.21 on the logarithmic scale), while accounting for important covariables. For a 1-SD increment in plasma endogenous ouabain, SBP, left ventricular posterior wall, the interventricular septum, and relative wall thickness increased by 1.59 mmHg (P = 0.009), 0.138 mm (P = 0.003), 0.152 mm (P = 0.013), and 0.71 x 10 (P = 0.008), respectively. In a sensitivity analysis, involving 431 individuals aged 29-71 years (10-90th percentile interval), a 1-SD increase in plasma endogenous ouabain was associated with opposite trends in ejection fraction (+0.90%, P = 0.005) and left ventricular systolic longitudinal strain (-0.48%, P = 0.011). Moreover, in individuals whose sodium excretion was above median (160 mmol/24 h), the aforementioned associations reached a higher level of statistical significance. Conclusion Our population-based study suggested that endogenous ouabain might have a trophic effect on the myocardium, independent of blood pressure and other covariables. The clinical implication of these findings remains to be elucidated.

Parent-of-origin specific linkage and association of the IGF2 gene region with birth weight and adult metabolic risk factors

Abstract: The maternally imprinted insulin-like growth factor 2 (IGF2) gene is an important fetal growth factor and is also suggested to have postnatal metabolic effects. In this study, we examined whether common polymorphisms in IGF2 (6815_6819delAGGGC, 1156T>C and 820G>A (ApaI)) and a microsatellite marker in the close vicinity of IGF2 were linked to or associated with birth weight and adult metabolic risk factors. Polymorphisms were genotyped in 199 monozygotic complete twin pairs, 109 dizygotic complete twin pairs, 15 single twins, 231 mothers and 228 fathers recruited from the East Flanders Prospective Twin Survey. Conventional and parent-of-origin specific linkage and association analyses were carried out with birth weight, adult body height and parameters quantifying obesity, insulin sensitivity and dyslipidaemia measured at adult age (mean age 25 years). In the parent-of-origin specific association analysis, in which only the paternally inherited allele was incorporated, the 1156T>C SNP (single nucleotide polymorphism) showed significant association with IGF-binding protein 1 (IGFBP1) levels (T and C (mean (95% CI)): 13.2 (12.1–14.3) and 16.2 (14.6–18.0) ng ml−1, P=0.002). No linkage was observed in either the conventional or in the parent-of-origin specific linkage analysis. This study suggests that paternally inherited alleles of a common polymorphism in the IGF2 gene affect IGFBP1 levels.

Left ventricular structure in relation to the human SAH gene in the European Project on Genes in Hypertension

Abstract: Left ventricular structure in relation to the human SAH gene in the European Project on Genes in Hypertension

The progress of patients in the European Working Party on Hypertension in the Elderly trial.

Abstract: 792 hypertensive patients above the age of 60 have entered the double-blind multicentre trial of the European Working Party on High blood pressure in the Elderly (EWPHE). Half were treated with hydrochlorothiazide and triamterene and half were given placebo and a second capsule was given and if necessary up to 2 g of methyldopa/day. The measurements in a sample of 157 patients suggested 80–86% compliance rate. A significant blood pressure difference of 25/10 mm Hg was obtained between the groups and maintained during five years of follow-up. The increase in serum creatinine found in the actively treated group was related to the decrease in sitting systolic blood pressure. Changes in serum uric acid correlated with changes in serum creatinine both in the placebo and in the actively treated group. Fasting blood glucose changed significantly in the active treatment group. The balance between this decreased risk on the basis of the blood pressurer eduction and the increase produced by the rise in blood glucose and the other treatment effects remains to be determined. The trial continues and more patients are being admitted.