Recommendations for evaluating compliance and persistence with hypertension therapy using retrospective data.
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Behavioral Research↗
Biomedical subjects
Michel Burnier
Publications and source records attributed to Michel Burnier.
Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients.
BACKGROUND: Chronic kidney disease (CKD) has been linked to higher heart failure (HF) risk. Anemia is a common consequence of CKD, and recent evidence suggests that anemia is a risk factor for HF. The purpose of this study was to examine among patients with HF, the association between CKD, anemia and inhospital mortality and early readmission. METHODS: We performed a retrospective cohort study in two Swiss university hospitals. Subjects were selected based the presence of ICD-10 HF codes in 1999. We recorded demographic characteristics and risk factors for HF. CKD was defined as a serum creatinine > or = 124 956;mol/L for women and > or = 133 micromol/L for men. The main outcome measures were inhospital mortality and thirty-day readmissions. RESULTS: Among 955 eligible patients hospitalized with heart failure, 23.0% had CKD. Twenty percent and 6.1% of individuals with and without CKD, respectively, died at the hospital (p < 0.0001). Overall, after adjustment for other patient factors, creatinine and hemoglobin were associated with an increased risk of death at the hospital, and hemoglobin was related to early readmission. CONCLUSION: Both CKD and anemia are frequent among older patients with heart failure and are predictors of adverse outcomes, independent of other known risk factors for heart failure.
Adolescent↗
[Nutrition and chronic renal failure: a puzzle!].
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Diet↗
Cardiac and vascular hypertrophy in Fabry disease: evidence for a new mechanism independent of blood pressure and glycosphingolipid deposition.
OBJECTIVE: Fabry disease is an X-linked disorder resulting from alpha-galactosidase A deficiency. The cardiovascular findings include left ventricular hypertrophy (LVH) and increased intima-media thickness of the common carotid artery (CCA IMT). The current study examined the possible correlation between these parameters. To corroborate these clinical findings in vitro, plasma from Fabry patients was tested for possible proliferative effect on rat vascular smooth muscle cells (vascular smooth muscle cell [VSMC]) and mouse neonatal cardiomyocytes. METHODS AND RESULTS: Thirty male and 38 female patients were enrolled. LVH was found in 60% of men and 39% of women. Increased CCA IMT was equally present in males and females. There was a strong positive correlation between LV mass and CCA IMT (r2=0.27; P<0.0001). VSMC and neonatal cardiomyocyte proliferative response in vitro correlated with CCA IMT (r2=0.39; P<0.0004) and LV mass index (r2=0.19; P=0.028), respectively. CONCLUSIONS: LVH and CCA IMT occur concomitantly in Fabry suggesting common pathogenesis. The underlying cause may be a circulating growth-promoting factor whose presence has been confirmed in vitro.
Adolescent↗
Proximal tubular function and salt sensitivity.
Blood pressure response to changes in dietary salt intake is highly variable among individuals. This heterogeneity results from the combined effects of genetic and environmental determinants. In recent years, considerable progress has been made in our understanding of the pathogenic mechanisms leading to the development of salt-sensitive hypertension. Much information has come from the investigation of rare monogenic forms of salt-sensitive hypertension, which has focused attention on alterations of renal sodium handling occurring essentially in the distal nephron. In this paper, we review the experimental, clinical, genetic, and epidemiologic evidence suggesting that proximal tubular function is also an important determinant of the blood pressure response to salt, which deserves greater attention.
Animals↗
Blockade of the renin-angiotensin-aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes.
Diabetes (particularly type 2 diabetes) represents a global health problem of epidemic proportions. Individuals with diabetes are not only more likely to develop hypertension, dyslipidemia, and obesity, but are also at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke. Angiotensin II plays a key pathophysiological role in the progression of diabetic renal disease, and blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II antagonists has therefore become an important therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. Several studies have demonstrated the effects of angiotensin II antagonists on the reduction of albuminuria and the progression of renal disease from microalbuminuria to macroalbuminuria. More importantly, several endpoint trials have shown that the antiproteinuric effects of losartan and irbesartan translate into cardiovascular and renoprotective benefits beyond blood pressure lowering, thereby delaying the need for dialysis or kidney transplantation by several years. These and other studies indicate that angiotensin II antagonists not only improve survival and quality of life of patients with diabetic nephropathy, but also have the potential to reduce the substantial healthcare burden associated with managing these patients. ACEi also appear to exert similar beneficial effects in diabetic patients, but whether clinically significant differences in renoprotection or mortality exist between angiotensin II antagonists and ACEi in patients with type 2 diabetes remains to be fully investigated in appropriate head-to-head studies.
Angiotensin II Type 1 Receptor Blockers↗
Effects of selective angiotensin II and beta1-receptor blockade on renal haemodynamics and sodium handling during orthostatic stress in healthy individuals.
BACKGROUND: Lower-body negative pressure (LBNP) induces a progressive activation of neurohormonal systems and a renal tubular and haemodynamic response that mimics the renal adaptation observed in congestive heart failure. Both angiotensin II receptor blockers and beta-blockers have been shown to reduce morbidity and mortality in patients with congestive heart failure. OBJECTIVE: To investigate whether part of the beneficial effects of angiotensin II receptor blockers and beta-blockers in congestive heart failure is mediated through an improvement in renal haemodynamics and sodium excretory capacity. METHODS AND RESULTS: The study was performed in healthy normotensive individuals exposed to three levels of LBNP and treated with placebo, 200 mg metoprolol once daily, or 16 mg candesartan once daily, for 10 days. Our results show that candesartan increased renal blood flow, and thereby blunted the vasoconstriction induced by LBNP. This effect was not found with metoprolol. More importantly, both metoprolol and candesartan prevented the sodium retention induced by LBNP, but only candesartan promoted sodium excretion during the 2-h recovery period--that is, once LBNP was interrupted. CONCLUSIONS: These results suggest that blockade of the renin-angiotensin and sympathetic nervous systems in heart failure may be beneficial in part as a result of improved sodium excretion.
Adrenergic beta-1 Receptor Antagonists↗
Association of CYP3A5 genotypes with blood pressure and renal function in African families.
OBJECTIVE: Renal cytochrome P450 3A5 (CYP3A5) activity has been associated with blood pressure and salt sensitivity in humans. We determined whether CYP3A5 polymorphisms are associated with ambulatory blood pressure (ABP) and with glomerular filtration rate (GFR) in African families. METHODS: Using a cross-sectional design, 375 individuals from 72 families, each with at least two hypertensive siblings, were recruited through a hypertension register in the Seychelles (Indian Ocean). We analyzed the association between the CYP3A5 alleles (*1, *3, *6 and *7) and ABP, GFR and renal sodium handling (fractional excretion of lithium), from pedigree data, allowing for other covariates and familial correlations. RESULTS: CYP3A5*1 carriers increased their daytime systolic and diastolic ABP with age (0.55 and 0.23 mmHg/year) more than non-carriers (0.21 and 0.04 mmHg/year). CYP3A5*1 had a significant main effect on daytime systolic/diastolic ABP [regression coefficient (SE): -29.6 (10.0)/-8.2 (4.1) mmHg, P = 0.003/0.045, respectively] and this effect was modified by age (CYP3A5*1 x age interactions, P = 0.017/0.018). For night-time ABP, the effect of CYP3A5*1 was modified by urinary sodium excretion, not by age. For renal function, CYP3A5*1 carriers had a 7.6(3.8) ml/min lower GFR (P = 0.045) than non-carriers. Proximal sodium reabsorption decreased with age in non-carriers, but not in CYP3A5*1 carriers (P for interaction = 0.02). CONCLUSIONS: These data demonstrate that CYP3A5 polymorphisms are associated with ambulatory BP, CYP3A5*1 carriers showing a higher age- and sodium- related increase in ABP than non-carriers. The age effect may be due, in part, to the action of CYP3A5 on renal sodium handling.
Adult↗
Comparative cardiovascular safety of traditional nonsteroidal anti-inflammatory drugs.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory and analgesic effects. Unfortunately, these drugs are not without toxicity, namely on the gastric mucosa, but also on the cardiovascular system. In this context, the marketing of the coxibs, a new series of NSAIDs that selectively inhibit COX-2, resulted in a large debate around their cardiovascular safety, because they may increase the incidence of myocardial infarction and stroke. The recent suspension of a large, randomised, controlled trial comparing celecoxib, naproxen and placebo in Alzheimer patients (the ADAPT trial) because of an apparent elevated cardiovascular risk in the naproxen group revived the debate on the cardiovascular safety of these drugs, but this time with special emphasis on the effect of traditional nonselective NSAIDs (tNSAIDs). In this paper that reviews and discusses the cardiovascular safety profile of tNSAIDs, essentially naproxen and ibuprofen in view of the most recent experimental and clinical data, the authors note that the published data are quite discordant and one cannot conclude that there is clear evidence to support a cardiovascular hazard from the administration of naproxen or non-naproxen NSAIDs unless additional information is provided. In addition, the results of retrospective case-control studies have to be interpreted very carefully because of the risk of confounding factors that are not always taken into account when subjects were classified either as cases or controls. Thus, in the absence of clear cut data, physicians will have to use traditional NSAIDs (or coxibs) in patients with a high cardiovascular risk on the basis of their common sense rather than on evidence-based medicine. For these patients, one should not forget that an inadequate long-term control of cardiovascular risk factors such as a hypertension, dyslipidaemia, diabetes, smoking and weight excess is more deleterious in terms of cardiovascular mortality than the administration of NSAIDs itself.
Anti-Inflammatory Agents, Non-Steroidal↗
Sustained 24-hour blockade of the renin-angiotensin system: a high dose of a long-acting blocker is as effective as a lower dose combined with an angiotensin-converting enzyme inhibitor.
Whether a higher dose of a long-acting angiotensin II receptor blocker (ARB) can provide as much blockade of the renin-angiotensin system over a 24-hour period as the combination of an angiotensin-converting enzyme inhibitor and a lower dose of ARB has not been formally demonstrated so far. In this randomized double-blind study we investigated renin-angiotensin system blockade obtained with 3 doses of olmesartan medoxomil (20, 40, and 80 mg every day) in 30 normal subjects and compared it with that obtained with lisinopril alone (20 mg every day) or combined with olmesartan medoxomil (20 or 40 mg). Each subject received 2 dose regimens for 1 week according to a crossover design with a 1-week washout period between doses. The primary endpoint was the degree of blockade of the systolic blood pressure response to angiotensin I 24 hours after the last dose after 1 week of administration. At trough, the systolic blood pressure response to exogenous angiotensin I was 58% +/- 19% with 20 mg lisinopril (mean +/- SD), 58% +/- 11% with 20 mg olmesartan medoxomil, 62% +/- 16% with 40 mg olmesartan medoxomil, and 76% +/- 12% with the highest dose of olmesartan medoxomil (80 mg) (P = .016 versus 20 mg lisinopril and P = .0015 versus 20 mg olmesartan medoxomil). With the combinations, blockade was 80% +/- 22% with 20 mg lisinopril plus 20 mg olmesartan medoxomil and 83% +/- 9% with 20 mg lisinopril plus 40 mg olmesartan medoxomil (P = .3 versus 80 mg olmesartan medoxomil alone). These data demonstrate that a higher dose of the long-acting ARB olmesartan medoxomil can produce an almost complete 24-hour blockade of the blood pressure response to exogenous angiotensin in normal subjects. Hence, a higher dose of a long-acting ARB is as effective as a lower dose of the same compound combined with an angiotensin-converting enzyme inhibitor in terms of blockade of the vascular effects of angiotensin.
Adult↗
[Drug industry influence on hypertension treatment trials].
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Antihypertensive Agents↗
Potassium supplementation reduces cardiac and renal hypertrophy independent of blood pressure in DOCA/salt mice.
We have demonstrated previously that deoxycorticosterone acetate (DOCA)/salt induces cardiac hypertrophy and left ventricular dysfunction independent of blood pressure (BP) in 1-renin gene mice. Because these mice also develop hypokalemia and metabolic alkalosis caused by mineralocorticoid excess, we investigated whether correcting hypokalemia by dietary potassium supplementation would prevent the DOCA/salt-induced cardiac hypertrophy, cardiac dysfunction, and electrocardiographic changes in normotensive, 1-renin gene and hypertensive, 2-renin gene mice. All mice were studied after 5 weeks of DOCA and salt administration. Potassium was given by adding 0.4 or 0.6% KCl to the drinking water. Our results show that correction of hypokalemia and metabolic alkalosis prevents cardiac hypertrophy and normalizes cardiac function without affecting BP in normotensive, 1-renin gene mice. In hypertensive, 2-renin gene mice, potassium supplementation induces a significant decrease in BP. The decrease in BP and correction of kalemia are associated with a significant but partial correction of cardiac hypertrophy. In both group of mice, electrocardiographic alterations were measured after administration of DOCA/salt, which could be corrected by potassium supplementation. Thus, these results show that correction of hypokalemia and metabolic alkalosis does prevent the development of cardiac hypertrophy and normalizes cardiac function independent of BP in normotensive, 1-renin gene mice that receive excess mineralocorticoid and salt. In 2-renin gene, hypertensive mice, potassium supplementation also prevents the development of cardiac hypertrophy, but the effect cannot be separated from the decrease in BP.
Animals↗
Determinants of persistence in hypertensive patients treated with irbesartan: results of a postmarketing survey.
BACKGROUND: Persistence is a key factor for long-term blood pressure control, which is of high prognostic importance for patients at increased cardiovascular risk. Here we present the results of a post-marketing survey including 4769 hypertensive patients treated with irbesartan in 886 general practices in Switzerland. The goal of this survey was to evaluate the tolerance and the blood pressure lowering effect of irbesartan as well as the factors affecting persistence in a large unselected population. METHODS: Prospective observational survey conducted in general practices in all regions of Switzerland. Previously untreated and uncontrolled pre-treated patients were started with a daily dose of 150 mg irbesartan and followed up to 6 months. RESULTS: After an observation time slightly exceeding 4 months, the average reduction in systolic and diastolic blood pressure was 20 (95% confidence interval (CI) -19.6 to -20.7 mmHg) and 12 mmHg (95% CI -11.4 to -12.1 mmHg), respectively. At this time, 26% of patients had a blood pressure < 140/90 mmHg and 60% had a diastolic blood pressure < 90 mmHg. The drug was well tolerated with an incidence of adverse events (dizziness, headaches,...) of 8.0%. In this survey more than 80% of patients were still on irbesartan at 4 month. The most important factors predictive of persistence were the tolerability profile and the ability to achieve a blood pressure target < or = 140/90 mmHg before visit 2. Patients who switched from a fixed combination treatment tended to discontinue irbesartan more often whereas those who abandoned the previous treatment because of cough (a class side effect of ACE-Inhibitors) were more persistent with irbesartan. CONCLUSION: The results of this survey confirm that irbesartan is effective, well tolerated and well accepted by patients, as indicated by the good persistence. This post-marketing survey also emphasizes the importance of the tolerability profile and of achieving an early control of blood pressure as positive predictors of persistence.
Aged↗
Glucose-containing peritoneal dialysis fluids regulate leptin secretion from 3T3-L1 adipocytes.
BACKGROUND: A marked elevation of serum leptin is observed soon after the start of peritoneal dialysis (PD), suggesting that leptin production may be stimulated by this treatment. Glucose metabolism is the major factor regulating leptin. The current study was designed to test if glucose-based PD fluids might regulate leptin production in vitro. METHODS: 3T3-L1 adipocytes were exposed to a 50:50 mixture of dialysis solutions and medium M199 containing 10% serum for <or=48 h. Leptin secretion in culture cell supernatants was measured by enzyme-linked immunosorbent assay and leptin mRNA content by northern blot analysis. RESULTS: The high glucose-based commercial dialysate PD4 produced a higher leptin secretion compared with an identical laboratory-manufactured dialysate (Lab-D), but with a physiological glucose concentration of 5 mM (P<0.05). Raising glucose concentration from 2.75 to 40 mM in Lab-D induced a dose-dependent increase in leptin secretion of <or=110+/-12% at 48 h (P<0.001) and leptin mRNA (P<0.05; glucose 2.75 vs 40 mM). Inhibition of UDP-N-acetylglucosamine biosynthesis, with 6-diazo-5-oxo-norleucine added to Lab-D, abolished most of the glucose-stimulated leptin release and downregulated leptin gene expression. Furthermore, glucose-free Lab-D supplemented with 1 mM glucosamine, an intermediate product in UDP-N-acetylglucosamine biosynthesis, increased leptin secretion by 28+/-11% over control (P<0.05), although without effect on leptin mRNA, after 48 h of culture. CONCLUSIONS: These results suggest that the PD-induced hyperleptinaemia could, in part, be mediated by the effect of glucose-based dialysis fluids on leptin production by adipocytes via activation of the hexosamine biosynthetic pathway.
3T3-L1 Cells↗
Pegylated interferon for the treatment of hepatitis C virus in haemodialysis patients.
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Adult↗
[Dialysis....at what cost?].
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Ethics, Medical↗
High heritability of ambulatory blood pressure in families of East African descent.
We estimated the heritability of ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) in east African families with at least 2 hypertensive siblings and living in the Seychelles islands (Indian Ocean). The sample consisted of 314 individuals (147 men and 167 women), both normotensive and hypertensive, from 76 pedigrees (mean+/-SD of 4.1+/-2.8 persons per pedigree). After a 2-week off-treatment period, daytime and nighttime ambulatory blood pressure (BP) was monitored. Office BP was measured with a standard mercury sphygmomanometer. We estimated by maximum likelihood the age- and sex-adjusted heritabilities from the additive polygenic component of the variance of the traits allowing for the presence of other familial correlations. We also adjusted for ascertainment (ie, for the fact that 2 siblings had to be hypertensive) and examined the effect of adjusting for body mass index, 24-hour urinary excretion of sodium and potassium, plasma renin activity, and plasma aldosterone concentration. Heritability estimates (+/-SE) for ambulatory SBP, DBP, and PP were, respectively, 0.37+/-0.12/0.24+/-0.12/0.54+/-0.12 for daytime and 0.34+/-0.13/ 0.37+/-0.15/0.47+/-0.12 for nighttime measurements (P<0.05 for all estimates). Heritability estimates for office SBP, DBP, and PP were, respectively, 0.20+/-0.11, 0.05+/-0.09, and 0.37+/-0.12. Heritability estimates for SBP varied markedly according to whether participants were treated for hypertension at baseline. The present data show that ambulatory BP and PP have a high heritability in families of African descent. They also demonstrate that antihypertensive treatment and the number of BP measurements have a major influence on the heritability estimates.
Adult↗
Heritability of renal function in hypertensive families of African descent in the Seychelles (Indian Ocean).
BACKGROUND: We estimated the heritability of three measures of glomerular filtration rate (GFR) in hypertensive families of African descent in the Seychelles (Indian Ocean). METHODS: Families with at least two hypertensive siblings and an average of two normotensive siblings were identified through a national hypertension register. Using the ASSOC program in SAGE (Statistical Analysis in Genetic Epidemiology), the age- and gender-adjusted narrow sense heritability of GFR was estimated by maximum likelihood assuming multivariate normality after power transformation. ASSOC can calculate the additive polygenic component of the variance of a trait from pedigree data in the presence of other familial correlations. The effects of body mass index (BMI), blood pressure, natriuresis, along with sodium to potassium ratio in urine and diabetes, were also tested as covariates. RESULTS: Inulin clearance, 24-hour creatinine clearance, and GFR based on the Cockcroft-Gault formula were available for 348 persons from 66 pedigrees. The age- and gender-adjusted correlations (+/- SE) were 0.51 (+/- 0.04) between inulin clearance and creatinine clearance, 0.53 (+/- 0.04) between inulin clearance and Cockcroft-Gault formula and 0.66 (+/- 0.03) between creatinine clearance and Cockcroft-Gault formula. The age- and gender-adjusted heritabilities (+/- SE) of GFR were 0.41 (+/- 0.10) for inulin clearance, 0.52 (+/- 0.13) for creatinine clearance, and 0.82 (+/- 0.09) for Cockcroft-Gault formula. Adjustment for BMI slightly lowered the correlations and heritabilities for all measurements whereas adjustment for blood pressure had virtually no effect. CONCLUSION: The significant heritability estimates of GFR in our sample of families of African descent confirm the familial aggregation of this trait and justify further analyses aimed at discovering genetic determinants of GFR.
Africa↗