Preserved capillary density of dorsal finger skin in treated hypertensive patients with or without type 2 diabetes

RESUME : La raréfaction des vaisseaux capillaires est une caractéristique de l'hypertension artérielle non traitée. Des données récentes indiquent que cette raréfaction peut être renversée par un traitement antihypertenseur chez les patients hypertendus non diabétiques. Malgré la fréquente association du diabète et de l'hypertension, on ne sait rien de la densité capillaire de patients diabétiques traités, souffrant d'hypertension artérielle. Nous avons dès lors recruté 21 patients normotendus (groupe contrôle), 25 patients souffrant uniquement d'hypertension artérielle , et 21 patients diabétiques (Diabète de type 2) souffrant également d'hypertension artérielle. Tous les patients hypertendus ont été traités avec un inhibiteur du système rénine-angiotensine, et une majorité présentait une tension artérielle moyenne en auto-contrôle à domicile de 135/85 mmHg ou moins. La densité capillaire a été évaluée par vidéomicroscopie sur la peau du dos des doigts et avec laser Doppler sur la peau de l'avant-bras (vasodilatation maximale induite par le chauffage local). Au final, il n'y avait pas de différence entre les groupes de l'étude, que ce soit lors des mesures de la densité capillaire sur le dos du doigt (groupe contrôle 101 ±11 capillaires, groupe des patients non- diabétiques hypertendus 99 ± 16, groupe des patients hypertendus et diabétiques 96 ± 18, p>0,5) ou lors des mesures de débit sanguin maximal sur la peau de l'avant-bras, un témoin indirect de la densité capillaire dans ce territoire (contrôles 666 ±114 unités de perfusion, non diabétique hypertendu 612 ± 126, hypertendus diabétiques 620 ±103, p> 0,5). En conclusion, notre étude est la première à démontrer que indépendamment de la présence ou non d'un diabète de type 2, la densité capillaire est normale chez les patients hypertendus présentant un contrôle raisonnable de la pression artérielle obtenue avec un bloqueur du système rénine-angiotensine.

Preserved capillary density of dorsal finger skin in treated hypertensive patients with or without type 2 diabetes.

OBJECTIVES: Capillary rarefaction is a hallmark of untreated hypertension. Recent data indicate that rarefaction may be reversed by antihypertensive treatment in nondiabetic hypertensive patients. Despite the frequent association of diabetes with hypertension, nothing is known on the capillary density of treated diabetic patients with hypertension. METHODS: We enrolled 21 normotensive healthy, 25 hypertensive only, and 21 diabetic (type 2) hypertensive subjects. All hypertensive patients were treated with a blocker of the renin-angiotensin system, and a majority had a home blood pressure ≤135/85 mmHg. Capillary density was assessed with videomicroscopy on dorsal finger skin and with laser Doppler imaging on forearm skin (maximal vasodilation elicited by local heating). RESULTS: There was no difference between any of the study groups in either dorsal finger skin capillary density (controls 101 ± 11 capillaries/mm(2) , nondiabetic hypertensive 99 ± 16, diabetic hypertensive 96 ± 18, p > 0.5) or maximal blood flow in forearm skin (controls 666 ± 114 perfusion units, nondiabetic hypertensive 612 ± 126, diabetic hypertensive 620 ± 103, p > 0.5). CONCLUSIONS: Irrespective of the presence or not of type 2 diabetes, capillary density is normal in hypertensive patients with reasonable control of blood pressure achieved with a blocker of the renin-angiotensin system.

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.

Blood pressure normalization in a large population of hypertensive patients treated with perindopril/indapamide combination: results of the OPTIMAX trial.

OBJECTIVE: To determine if the fixed-dose perindopril/indapamide combination (Per/Ind) normalizes blood pressure (BP) in the same fraction of hypertensive patients when treated in everyday practice or in controlled trials. METHODS: In this prospective trial, 17 938 hypertensive patients were treated with Per 2 mg/Ind 0.625 mg for 3-6 months. In Group 1 Per/Ind was initiated in newly diagnosed patients (n = 7032); in Group 2 Per/Ind replaced previous therapy in patients already treated but having either their BP still uncontrolled or experiencing side-effects (n = 7423); in Group 3 Per/Ind was added to previous treatment in patients with persistently high BP (n = 3483). BP was considered normalized when &lt; or = 140/90 mm Hg. A multivariate analysis for predictors of BP normalization was performed. RESULTS: Subjects were on average 62 years old and had a baseline BP of 162.3/93.6 mm Hg. After treatment with Per/Ind, BP normalization was reached in 69.6% of patients in the Initiation group, 67.5% in the Replacement Group, and 67.4% in the Add-on Group (where patients were more frequently at risk, diabetic, or with target organ damage). Mean decreases in systolic BP of 22.8 mm Hg and in diastolic BP of 12.4 mm Hg were recorded. CONCLUSIONS: This trial was established to reflect everyday clinical practice, and a treatment strategy based on the Per/Ind combination, administered as initial, replacement, or add-on therapy, led to normalization rates that were superior to those observed in Europe in routine practice. These results support recent hypertension guidelines which encourage the use of combination therapy in the management of arterial hypertension.

Double-blind comparison of indapamide with a placebo in hypertensive patients treated by practicing physicians.

The antihypertensive effect of indapamide (2.5 mg/day) was compared to that obtained with a placebo in a controlled trial carried out by 11 physicians in their private practice. Thirty-one patients with uncomplicated essential hypertension were included. After a run-in period of 3 weeks without any treatment, either indapamide (n = 16) or a placebo (n = 15) were administered for 8 weeks in double-blind fashion. Blood pressure decreased in both groups. In patients treated with indapamide, systolic pressure was significantly lower than in those given the placebo at 3 out of the 4 follow-up visits; diastolic pressure, however, was significantly lower only at the end of the trial. Both the active drug and the placebo were well tolerated. No significant change in body weight, plasma potassium and uric acid occurred during the study in either group of patients. It appears therefore that indapamide, at a dose which apparently has no major diuretic effect, may be useful for practitioners in managing patients with mild to moderate hypertension.

Comparison of betaxolol with verapamil in hypertensive patients: discrepancy between office and ambulatory blood pressures.

The purpose of this study was to compare in the individual hypertensive patient the blood pressure lowering effect of a beta-blocking agent i.e. betaxolol with that of a calcium entry blocker, i.e. verapamil. The antihypertensive efficacy of the drugs was evaluated both at the physician's office and by monitoring ambulatory daytime blood pressure using a portable blood pressure recorder (Remler M2000). Seventeen patients with uncomplicated essential hypertension (aged 35-67 years) were treated for two consecutive 6-week periods with either betaxolol, 20 mg/day or a slow-release formulation of verapamil, 240-480 mg/day. The sequence of treatment phases was randomly allocated and a 2-week wash-out period preceded each treatment. Both betaxolol and verapamil had a significant blood pressure lowering effect when assessed at the physician's office. However, ambulatory recorded blood pressures were significantly reduced only with betaxolol. In the presence of a physician, the best responders to betaxolol tended to be also the best responders to verapamil, whereas there was no relationship between the fall in ambulatory recorded blood pressure observed during betaxolol and the corresponding fall during verapamil administration. The blood pressure response to both betaxolol and verapamil was not related to age.

9C.09: TREATMENT WITH CANDESARTAN UNMASKS HIGHER URINARY NOREPINEPHRINE EXCRETION IN WHITE COAT HYPERTENSIVE PATIENTS COMPARED TO HEALTHY NORMOTENSIVE PARTICIPANTS.

OBJECTIVE: White coat hypertensive is a pre-hypertensive state that has been associated with increased sympathetic drive. The objective of the study was to compare the exposure of the kidney to sympathetic nerve activity using urinary normetanephrine (UNMN) as a marker of renal sympathetic exposure in white coat hypertensive (WCH) and healthy normotensive (HN) participants. DESIGN AND METHOD: This was a double-blind randomized placebo-controlled crossover study. WCH were included if office blood pressure was >140/80 mmHg and ambulatory blood pressure <135/85 mmHg and HN if OBP was <140/90 mmHg and ABP <135/85 mmHg Participants were randomized to receive either 16 mg of candesartan or a matched placebo for one week before study day. On the study day systemic and renal hemodynamics as well as plasma norepinephrine and urinary excretion of normetanephrine (measured by LC/MS-MS were measured after one hour of baseline, one hour of lower body negative pressure and one hour of recovery period. Excretion of UNMN was expressed as the total of UNMN excreted during these three hours (cumUNMN). Paired or unpaired t-test were used for comparison. RESULTS: 25 HN and 12 WCH participants were included in the study. Mean age (±standard deviation), BMI were respectively 31.0±10.5 years and 22.0 ± 2.2 Kg/m2 in HN and 40.7±17.8 years and 26.7 ± 6.3 Kg/m2 in WCH.Table 1 Baseline mean blood pressure, plasma noradrenaline and cumulated UNMN during placebo and candesartan(Figure is included in full-text article.)Mean blood pressure was higher during placebo and candesartan in WCH compared to HN. Cumulated UNMN was higher in both groups after candesartan treatment. Cumulated UNMN was higher in WCH than in HN only after candesartan treatment. CONCLUSIONS: Urinary excretion of normetanephrine is increased in WCH compared to HN when treated with candesartan. The increased excretion of uNMN when the renin angiotensin system is blocked might reflect an increased sensitivity of WCH to stress conditions such as orthostatic stress.

Comparative Effect of a Renin Inhibitor and a Thiazide Diuretic on Renal Tissue Oxygenation in Hypertensive Patients.

BACKGROUND/AIMS: The purpose of the present study was to compare the direct renin inhibitor aliskiren to the diuretic hydrochlorothiazide (HCTZ) in their ability to modulate renal tissue oxygenation in hypertensive patients. METHODS: 24 patients were enrolled in this randomized prospective study and 20 completed the protocol. Patients were randomly assigned to receive either aliskiren 150-300 mg/d or HCTZ 12.5 - 25 mg/d for 8 weeks. Renal oxygenation was measured by BOLD-MRI at weeks 0 and 8. BOLD-MRI was also performed before and after an i.v. injection of 20 mg furosemide at week 0 and at week 8. BOLD-MRI data were analyzed by measuring the oxygenation in 12 computed layers of the kidney enabling to asses renal oxygenation according to the depth within the kidney and by the classical method of regions of interest (ROI). RESULTS: The classical ROI analysis of the data showed no difference between the groups at week 8. The analysis of renal oxygenation according to the 12 layers method shows no significant difference between aliskiren and HCTZ at week 8 before administration of furosemide. However, within group analyses show that aliskiren slightly but not significantly increased oxygenation in the cortex and decreased medullary oxygenation whereas HCTZ induced a significant overall decrease in renal tissue oxygenation. With the same method of analysis we observed that the response to furosemide was unchanged in the HCTZ group at week 8 but was characterized by an increase in both cortical and medullary oxygenation in aliskiren-treated patients. Patients responding to aliskiren and HCTZ by a fall in systolic blood pressure of >10 mmHg improved their renal tissue oxygenation when compared to non-responders. CONCLUSION: With the classical method of evaluation using regions no difference were found between aliskiren and HCTZ on renal tissue oxygenation after 8 weeks. In contrast, with our new method that takes into account the entire kidney, within group analyses show that aliskiren slightly increases cortical and medullary renal tissue oxygenation in hypertensive patients whereas HCTZ decreases significantly renal oxygenation at trough.

Ambulatory blood pressure monitoring in adolescent untreated hypertensive patients.

Ambulatory blood pressure profiles were obtained with the portable semi-automatic blood pressure recorder Remler M2000 in groups of 20 adolescents, 20 young and 20 middle-aged adults and 20 elderly untreated patients, all considered by their physician to be hypertensive. It was found that adolescents who are hypertensive when seeing their physician are more often normotensive outside the physician's office than adult and elderly patients under similar conditions. The increased heart rate variability which was detected in adolescents was not associated with an enhanced blood pressure variability.

Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients.

OBJECTIVE: To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily. PATIENTS: Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study. STUDY DESIGN: After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment. RESULTS: Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening). CONCLUSIONS: Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.

NYVAC immunization induces polyfunctional HIV-specific T-cell responses in chronically-infected, ART-treated HIV patients.

We report the results of the Theravac-01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus-based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC-B vaccine was injected intra-muscularly into ten HIV-infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV-specific T-cell responses following immunization were quantitatively analyzed using an IFN-γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC-B vaccine is safe and highly immunogenic, as indicated by increased HIV-specific T-cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T-cell responses, and the appearance of newly detected HIV-specific CD4(+) and CD8(+) T-cell responses were observed. Furthermore, immunization mostly induced an increase in Gag-specific T-cell responses. In conclusion, NYVAC-B immunization induces broad, vigorous, and polyfunctional HIV-specific T-cell responses, suggesting that poxvirus-based vaccine regimens may be instrumental in the therapeutic HIV vaccine field.

Should hypertensive patients take vitamin d?

The prevalence of both hypertension and vitamin D deficiency is high. The discovery of the vitamin D receptor and its possible effects on components of the cardiovascular system influencing blood pressure, such as the renin angiotensin system, the heart, the kidney and the blood vessels, has generated the hope that vitamin D therapy could be a new target for the treatment for hypertensive patients. Cross-sectional studies have clearly shown an association between low levels of vitamin D and hypertension. This association is not as clear in longitudinal studies. Finally, evidence from randomized controlled trials specifically designed to test the hypothesis of a blood pressure lowering effect of vitamin D is weak. Therefore, there is actually not enough evidence to recommend giving vitamin D to reduce blood pressure in hypertensive patients.

Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diurectic in hypertensive patients of African descent

Résumé de la thèse en français Titre : Différence entre hommes et femmes dans la réponse à un inhibiteur de l'enzyme de conversion de l'angiotensine et un diurétique chez des patients hypertendus d'origine Africaine. Introduction: L'efficacité des inhibiteurs de l'enzyme de conversion de l'angiotensine (ACEI) dans le traitement de l'hypertension artérielle chez les patients africains est controversée. Objectif: Nous avons examiné la baisse de la tension artérielle ambulatoire (ABP) en réponse à un diurétique et un ACEI chez des patients hypertendus d'origine africaine et nous avons évalué les différentes caractéristiques déterminant l'efficacité du traitement. Méthodes: Etude en simple-aveugle randomisée, en crossover AB/BA. Arrangement Familles hypertendues d'origine africaine de la population générale des Seychelles. Participants : 52 patients (29 hommes et 23 femmes) sur 62 patients hypertendus éligibles ont été inclus. Le principal résultat était la mesure de la réponse de l'ABP à 20 mg de lisinopril (LIS) ou 25 mg d'hydrochlorothiazide (HCT) quotidiennement pendant quatre semaines. Résultats: Le jour, la réponse systolique/diastolique de l'ABP sous HCT était de 4.9 (95% intervalle de confiance (IC) 1.2-8.6)/3.6 (1.0-6.2) mm Hg pour les hommes et 12.9 (9.216.6)/6.3 (3.7-8.8) mm Hg pour les femmes. Sous LIS, la réponse était de 18.8 (15.022.5)/14.6 (12.0-17.1) mm Hg pour les hommes et de 12.4 (8.7-16.2)/7.7 (5.1-10.2) mm Hg pour les femmes. La nuit, la réponse systolique/diastolique sous HCT était de 5.0 (0.6-9.4)/2.7 ((-0.4)-5.7) mm Hg pour les hommes et de 11.5 (7.1-16.0)/5.7 (2.6-8.8) mm Hg pour les femmes, et sous LIS était de 18.7 (14.2-22.1)/15.4 (12.4-18.5) mm Hg pour les hommes et de 3.5 ((-1.0)-7.9)/2.3 ((-0.8)-5.4) mm Hg pour les femmes. L'analyse de régression linéaire multiple a montré que le sexe est un prédicteur indépendant de la réponse tensionnelle à l'HCT et au LIS. Conclusions : Les patients hypertendus d'origine africaine ont présenté une baisse tensionnelle plus grande en réponse au LIS qu'à l'HCT. Les hommes ont mieux répondu au LIS qu'à l'HCT alors que les femmes ont répondu de manière similaire aux deux traitements.

Physicians' estimates of the 10 year cardiovascular risk in hypertensive patients: an evaluation in primary care physicians in training.

To evaluate how young physicians in training perceive their patients' cardiovascular risk based on the medical charts and their clinical judgment. Cross sectional observational study. University outpatient clinic, Lausanne, Switzerland. Two hundred hypertensive patients and 50 non-hypertensive patients with at least one cardiovascular risk factor. Comparison of the absolute 10-year cardiovascular risk calculated by a computer program based on the Framingham score and adapted for physicians by the WHO/ISH with the perceived risk as assessed clinically by the physicians. Physicians underestimated the 10-year cardiovascular risk of their patients compared to that calculated with the Framingham score. Concordance between methods was 39% for hypertensive patients and 30% for non-hypertensive patients. Underestimation of cardiovascular risks for hypertensive patients was related to the fact they had a stabilized systolic blood pressure under 140 mm Hg (OR = 2.1 [1.1; 4.1]). These data show that young physicians in training often have an incorrect perception of the cardiovascular risk of their patients with a tendency to underestimate the risk. However, the calculated risk could also be slightly overestimated when applying the Framingham Heart Study model to a Swiss population. To implement a systematic evaluation of risk factors in primary care a greater emphasis should be placed on the teaching of cardiovascular risk evaluation and on the implementation of quality improvement programs.

Reactive rise in blood pressure upon cuff inflation : cuff inflation at the arm causes a greater rise in pressure than at the wrist in hypertensive patients

Résumé en français: Il est admis que l'inflation d'une manchette à pression au niveau du bras engendre une augmentation réactionnelle de la tension artérielle qui peut être le résultat d'une gêne lors de l'inflation et peut diminuer la précision de la mesure. Dans cette étude, nous comparons séquentiellement l'augmentation de la tension artérielle lorsque la manchette à pression est positionnée au niveau du bras et au niveau du poignet. Nous avons étudié un collectif de 34 participants normotendus et 34 patients hypertendus. Chacun d'eux était équipé de deux manchettes à pression, l'une au niveau du bras et l'autre au niveau du poignet. Nous avons randomisé l'ordre d'inflation des manchettes ainsi que la pression d'inflation maximale (180mmHg versus 240mmHg). Trois mesures étaient effectuées pour chaque pression d'inflation maximale, ceci au bras comme poignet, et leur séquence était également randomisée. En parallèle, un enregistrement continu de la tension artérielle avait lieu au niveau du majeur de la main opposée à l'aide d'un photoplethysmographe. Cette valeur était considérée comme la valeur de tension artérielle au repos. Pour les participants normotendus, aucune différence statistiquement significative n'a pu être mise en évidence en lien avec la position de la manchette à pression, ceci indépendamment de la pression d'inflation maximale. Variation de la pression systolique à 180 mmHg: 4.3+/-3.0 mmHg au bras et 3.7+/-2.9 mmHg au poignet (p=ns), à 240 mmHg: 5.5+/-3.9 au bras et 4.2+/-2.7 mmHg au poignet (p=0.052). En revanche, concernant les patients hypertendus, une augmentation significative de la tension artérielle a été mise en évidence entre le bras et le poignet. Ceci pour les valeurs de tension artérielle systolique et diastolique et quelle que soit la pression d'inflation maximale utilisée. Augmentation de la pression artérielle systolique 6.513.5 mmHg au bras et 3.812.1mmHg au poignet pour une pression d'inflation maximale de 180 mmHg (p<0.01) et respectivement 6.413.5 mmHg et 4.713.0 mmHg pour 240 mmHg (p=0.01). L'augmentation des valeurs de tension artérielle était indépendante de la valeur tensionnelle de base. Ces résultats montrent que les patients hypertendus réagissent significativement moins à l'inflation d'une manchette ä pression lorsque celle-ci est positionnée au niveau du poignet par rapport au bras, ceci indépendamment des valeurs de tension artérielle de base des patients. Nous pouvons donc suggérer que l'inflation d'une manchette à pression cause moins de désagrément lorsqu'elle est placée au niveau du poignet, notamment chez les patients hypertendus et qu'elle peut être une alternative à la mesure standard au niveau du bras.