Upward Shift and Steepening of the Blood Pressure Response to Exercise in Hypertensive Subjects at High Altitude.

BACKGROUND: Acute exposure to high-altitude hypobaric hypoxia induces a blood pressure rise in hypertensive humans, both at rest and during exercise. It is unclear whether this phenomenon reflects specific blood pressure hyperreactivity or rather an upward shift of blood pressure levels. We aimed at evaluating the extent and rate of blood pressure rise during exercise in hypertensive subjects acutely exposed to high altitude, and how these alterations can be counterbalanced by antihypertensive treatment. METHODS AND RESULTS: Fifty-five subjects with mild hypertension, double-blindly randomized to placebo or to a fixed-dose combination of an angiotensin-receptor blocker (telmisartan 80 mg) and a calcium-channel blocker (nifedipine slow release 30 mg), performed a cardiopulmonary exercise test at sea level and after the first night's stay at 3260 m altitude. High-altitude exposure caused both an 8 mm Hg upward shift (P<0.01) and a 0.4 mm Hg/mL/kg per minute steepening (P<0.05) of the systolic blood pressure/oxygen consumption relationship during exercise, independent of treatment. Telmisartan/nifedipine did not modify blood pressure reactivity to exercise (blood pressure/oxygen consumption slope), but downward shifted (P<0.001) the relationship between systolic blood pressure and oxygen consumption by 26 mm Hg, both at sea level and at altitude. Muscle oxygen delivery was not influenced by altitude exposure but was higher on telmisartan/nifedipine than on placebo (P<0.01). CONCLUSIONS: In hypertensive subjects exposed to high altitude, we observed a hypoxia-driven upward shift and steepening of the blood pressure response to exercise. The effect of the combination of telmisartan/nifedipine slow release outweighed these changes and was associated with better muscle oxygen delivery. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830530.

Blood pressure changes in patients with chronic heart failure undergoing slow breathing training.

BACKGROUND: Slow breathing training (SBT) has been proposed as a new non-pharmacological treatment able to induce favorable effects in patients with chronic heart failure (CHF). However, no information is available regarding its effects on orthostatic blood pressure (BP) changes in these patients, an issue of practical relevance given the reported BP-lowering effect of SBT. The aim of this study is to evaluate the influence of SBT on BP and whether SBT induces orthostatic hypotension (OH) or changes in quality of life (QoL) in CHF patients. METHODS: The analysis was performed as part of an ongoing crossover open trial aimed at assessing the clinical effectiveness of SBT in treated patients with CHF. The patients underwent 10-12 weeks of SBT with the RESPeRATE device and 10-12 week follow-up under usual care. Patients were randomly divided into two groups: group I began with SBT, followed by usual care; group II began with usual care, followed by SBT. Patients undergoing SBT were asked to perform each day two separate 15 min sessions of device-guided SBT at a breathing frequency of 6 breaths/min. In all patients, before the enrollment and after each study phase, clinical data collection and BP measurements in sitting, supine and standing position were performed. OH was defined as a decrease of ≥ 20 mmHg in systolic blood pressure (SBP) or ≥ 10 mmHg in diastolic blood pressure (DBP) within 3 min of standing. QoL was assessed three times at the beginning, and after each phase of the study by the Minnesota Living with Heart Failure (MLHF) questionnaire. RESULTS: Forty patients (two equal groups) completed the study, with the following baseline characteristics: 32 males/eight females, age 63.3 ± 13.4 years, 25 with ischemic CHF, 37 in New York Heart Association class II and three in class III, left ventricular ejection fraction 30.8 ± 6.7%, mean BP 138.7 ± 16.5/83.1 ± 11.5 mmHg, 23 with arterial hypertension and four with a history of stroke. There were no significant differences between the groups in clinical characteristics, SBP and DBP at rest, while seated and before and after standing up. OH prevalence was low and did not change during the study (10% vs 10%). No significant difference in average SBP and DBP changes secondary to body position were found when comparing the two study phases. Decrease in MLHF score was observed in group I during SBT (p = 0.002), but not in group II. CONCLUSIONS: Our data indicate that SBT is safe, does not affect the prevalence of OH in CHF patients and shows a non-significant tendency to improve QoL. These results should be confirmed in a larger sample of patients to support the safety of SBT and its possible benefits as a novel component of cardiorespiratory rehabilitation programs in CHF.

Blood pressure control by the nifedipine GITS-telmisartan combination in patients at high cardiovascular risk: the TALENT study.

BACKGROUND: Guidelines on hypertension regard combinations between two antihypertensive drugs to be the most important treatment strategy. Because of the complementary mechanism of action and the evidence of cardiovascular protective effects they include the combination of a calcium antagonist and an angiotensin receptor antagonist among the priorital ones to employ. AIMS: To determine in hypertensive patients at high cardiovascular risk whether combining Nifedipine GITS at low dose and telmisartan reduced ambulatory and clinic blood pressure (BP) more than the combination components, controlled BP early after treatment initiation and allowed to also obtain a better long-term BP control compared to initiating treatment with the combination components and moving to the combination later. METHODS: Four hundred and five patients with a clinic SBP ≥ 135 mmHg and with diabetes, a metabolic syndrome or organ damage were randomized to once-a-day telmisartan 80 mg, nifedipine GITS 20 mg or the combination of the two drugs in a 1: 1: 2 ratio for 8 weeks in the context of a multicenter double-blind study design. Patients on monotherapy were then moved to combination treatment and all three groups were followed for an additional 16-week period. Both 24-h and clinic BP were measured before treatment and at various times during treatment. RESULTS: In the per-protocol patients (n = 327), baseline demographic and clinical characteristics were similar between the three groups. Baseline 24-h SBP values were 136.2 ± 11.6 mmHg (mean ± SD), 137.2 ± 12.5 mmHg and 136.8 ± 11.7 mmHg in the telmisartan monotherapy, nifedipine GITS monotherapy and combination therapy, respectively. The corresponding clinic values were 151.7 ± 11.8, 151.3 ± 11.9 and 151.1 ± 11.8 mmHg, respectively. All treatments lowered 24-h SBP significantly (P < 0.0001) but combination treatment (8 weeks) reduced it significantly more than monotherapies (10.8 ± 0.8 vs. 6.6 ± 1.1 mmHg and 8.0 ± 1.2 mmHg; P = 0.001 and 0.037). Similar data were obtained for clinic SBP for which the combination showed a significantly greater BP reduction (12.6 ± 0.6 vs. 8.6 ± 0.7 mmHg and 9.3 ± 0.8 mmHg; P = 0.003 and 0.024) also after 2 weeks of treatment. Moving from monotherapy to combination therapy increased the antihypertensive effect and made both ambulatory and clinic SBP superimposable in the three groups after 16 and 24 weeks of treatment. Similar findings were obtained for DBP. CONCLUSION: Combination treatment with nifedipine GITS low dose and telmisartan provides a greater and earlier clinic and ambulatory BP reduction than the combination components in monotherapy. Initiating treatment with the combination did not result in any better longer term BP control compared to starting treatment with monotherapy and moving to the combination later.