Time in Therapeutic Range, as a Determinant of All-Cause Mortality in Patients With Hypertension.

BACKGROUND: Accumulating evidence indicates that reducing systolic blood pressure (BP) tooutcomes; however, an optimal level has not yet been determined. Many population studies or post hoc analyses suggest a target systolic BP between 120 and 140 mm Hg with increased risk above and below that range. We tested the hypothesis that consistent control of systolic BP between 120 and 140 mm Hg-time in therapeutic range-is a strong determinant of all-cause mortality among US veterans. METHODS AND RESULTS: A total of 689 051 individuals from 15 Veterans Administration Medical Centers were followed over a 10-year period. Participants were classified as hypertensive, intermediate hypertensive, and normotensive according to the number of elevated BP recordings (\u3e3, 1 or 2, and none, respectively). Time within, above, or below therapeutic range (120-140 mm Hg) was considered in quartiles and related to all-cause mortality. The study population consisted of 54% hypertensive, 19.9% intermediate, and 26.1% normotensive participants; the corresponding mortality rates for the 3 groups were 11.5%, 8%, and 1.9%, respectively (P75%) to 8.9%, 15.6%, and 23.5% towards the less consistently controlled quartiles (50-75%, 25-50%, and CONCLUSIONS: An inverse and gradual association between time in therapeutic range and all-cause mortality was observed in this large veteran cohort. Consistency of BP control over time is a strong determinant of all-cause mortality, and consistency of BP control should be monitored in everyday clinical practice

Common Secondary Causes of Resistant Hypertension and Rational for Treatment

Resistant hypertension is defined as uncontrolled blood pressure despite the use of three antihypertensive drugs, including a diuretic, in optimal doses. Treatment resistance can be attributed to poor adherence to antihypertensive drugs, excessive salt intake, physician inertia, inappropriate or inadequate medication, and secondary hypertension. Drug-induced hypertension, obstructive sleep apnoea, primary aldosteronism, and chronic kidney disease represent the most common secondary causes of resistant hypertension. Several drugs can induce or exacerbate pre-existing hypertension, with non-steroidal anti-inflammatory drugs being the most common due to their wide use. Obstructive sleep apnoea and primary aldosteronism are frequently encountered in patients with resistant hypertension and require expert management. Hypertension is commonly found in patients with chronic kidney disease and is frequently resistant to treatment, while the management of renovascular hypertension remains controversial. A step-by-step approach of patients with resistant hypertension is proposed at the end of this review paper

Carotid Baroreceptor Stimulation for the Treatment of Resistant Hypertension

Interventional activation of the carotid baroreflex has been an appealing idea for the management of resistant hypertension for several decades, yet its clinical application remained elusive and a goal for the future. It is only recently that the profound understanding of the complex anatomy and pathophysiology of the circuit, combined with the accumulation of relevant experimental and clinical data both in animals and in humans, has allowed the development of a more effective and well-promising approach. Indeed, current data support a sustained over a transient reduction of blood pressure through the resetting of baroreceptors, and technical deficits have been minimized with a subsequent recession of adverse events. In addition, clinical outcomes from the application of a new implantable device (Rheos) that induces carotid baroreceptor stimulation point towards a safe and effective blood pressure reduction, but longer experience is needed before its integration in the everyday clinical practice. While accumulating evidence indicates that carotid baroreceptor stimulation exerts its benefits beyond blood pressure reduction, further research is necessary to assess the spectrum of beneficial effects and evaluate potential hazards, before the extraction of secure conclusions

Benefits from Treatment and Control of Patients with Resistant Hypertension

Resistant hypertension is commonly found in everyday clinical practice. However, the risks of resistant hypertension, as well as the benefits of treatment and control of blood pressure in patients with resistant hypertension remain vaguely clarified. Data from small clinical studies and observational cohorts suggest that patients with resistant hypertension are at increased cardiovascular risk, while control of blood pressure offers substantial benefits. It has to be noted however that data from appropriate large randomized studies are missing, and resistant hypertension remains remarkably understudied. Resistant hypertension has attracted significant scientific interest lately, as new therapeutic modalities become available. The interventional management of resistant hypertension either by carotid baroreceptor stimulation or renal sympathetic denervation is currently under investigation with promising preliminary results. This review presents available evidence regarding the benefits of treatment and control of blood pressure in patients with resistant hypertension and offers a critical evaluation of existing data in this field

Statin therapy, fitness, and mortality risk in middle-aged hypertensive male veterans

BACKGROUND Hypertension often coexists with dyslipidemia, accentuating cardiovascular risk. Statins are often prescribed in hypertensive individuals to lower cardiovascular risk. Higher fitness is associated with lower mortality, but exercise capacity may be attenuated in hypertension. The combined effects of fitness and statin therapy in hypertensive individuals have not been assessed. Thus, we assessed the combined health benefits of fitness and statin therapy in hypertensive male subjects. METHODS Peak exercise capacity was assessed in 10,202 hypertensive male subjects (mean age = 60.4±10.6 years) in 2 Veterans Affairs Medical Centers. We established 4 fitness categories based on peak metabolic equivalents (METs) achieved and 8 categories based on fitness status and statin therapy. RESULTS During the follow-up period (median = 10.2 years), there were 2,991 deaths. Mortality risk was 34% lower (hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.59–0.74; P \u3c 0.001) among individuals treated with statins compared with those not on statins. The fitness-related mortality risk association was inverse and graded regardless of statin therapy status. Risk reduction associated with exercise capacity of 5.1–8.4 METs was similar to that observed with statin therapy. However, those achieving ≥8.5 METs had 52% lower risk (HR = 0.48; 95% CI = 0.37–0.63) when compared with the least-fit subjects (≤5 METs) on statin therapy. CONCLUSIONS The combination of statin therapy and higher fitness lowered mortality risk in hypertensive individuals more effectively than either alone. The risk reduction associated with moderate increases in fitness was similar to that achieved by statin therapy. Higher fitness was associated with 52% lower mortality risk when compared with the least fit subjects on statin therapy

Cardiorespiratory fitness and incidence of type 2 diabetes in United States veterans on statin therapy

Impact of cardiorespiratory fitness on statin-related incidence of type 2 diabetes has not been assessed. We assessed the cardiorespiratory fitness and diabetes incidence association in dyslipidemic patients on statins.We identified dyslipidemic patients with a normal exercise test performed during 1986 and 2014 at the Veterans Affairs Medical Centers in Washington, DC or Palo Alto, Calif. The statin-treated patients (n\ua0= 4092; age\ua0= 58.8 ± 10.9 years) consisted of 2701 Blacks and 1391 Whites. None had evidence of type 2 diabetes prior to statin therapy. We formed 4 fitness categories based on age and peak metabolic equivalents achieved: Least-fit (n\ua0= 954), Low-fit (n\ua0= 1201), Moderate-fit (n\ua0= 1242), and High-fit (n\ua0=\ua0695). The non-statin-treated cohort (n\ua0= 3001; age\ua0= 57.2 ± 11.2 years) with no evidence of type 2 diabetes prior to the exercise test served as controls.Diabetes incidence was 24% higher in statin-treated compared with non-statin-treated patients (

Exercise Capacity and All-Cause Mortality in African American and Caucasian Men With Type 2 Diabetes

OBJECTIVE - The purpose of this study was to assess the association between exercise capacity and mortality in African Americans and Caucasians with type 2 diabetes and to explore racial differences regarding this relationship. RESEARCH DESIGN AND METHODS - African American (n = 1,703; aged 60 ± 10 years) and Caucasian (n = 1,445; aged 62 ± 10 years) men with type 2 diabetes completed a maximal exercise test between 1986 and 2007 at the Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California. Three fitness categories were established (low-, moderate-, and high-fit) based on peak METs achieved. Subjects were followed for all-cause mortality for 7.3 ± 4.7 years. RESULTS - The adjusted mortality risk was 23% higher in African Americans than in Caucasians (hazard ratio 1.23 [95% CI 1.1-1.4]). A graded reduction in mortality risk was noted with increased exercise capacity for both races. There was a significant interaction between race and METs (P \u3c 0.001) and among race and fitness categories (P \u3c 0.001). The association was stronger for Caucasians. Each 1-MET increase in exercise capacity yielded a 19% lower risk for Caucasians and 14% for African Americans (P \u3c 0.001). Similarly, the risk was 43% lower (0.57 [0.44- 0.73]) for moderate-fit and 67% lower (0.33 [0.22-0.48]) for high-fit Caucasians. The comparable reductions in African Americans were 34% (0.66 [0.55-0.80]) and 46% (0.54 [0.39-0.73]), respectively. CONCLUSIONS - Exercise capacity is a strong predictor of all-cause mortality in African American and Caucasian men with type 2 diabetes. The exercise capacity-related reduction in mortality appears to be stronger and more graded for Caucasians than for African Americans. © 2009 by the American Diabetes Association

Characterization and history of arterial hypertension leading to inpatient treatment

BACKGROUND AND AIMS: Arterial hypertension is a major cause of death worldwide. For the most part, treatment for hypertension can be performed on an outpatient basis. However, some patients also require inpatient treatment, and the contributing factors for this remain unknown. Therefore, the primary objective of the present study was to determine which patient characteristics are associated with inpatient treatment for arterial hypertension. METHODS: Here, we conducted a mono-centric study of 103 hypertensive subjects, who were treated as inpatients in the Department of Nephrology and rheumatology of the university medical faculty of Göttingen. Therapies were not altered, and data collection was performed retrospectively. In addition to epidemiological information, the following data were recorded: patient symptoms, blood pressure (BP), anti-hypertensive therapy, and concomitant diseases (e.g., renal and cardiovascular conditions). RESULTS: Approximately half (53 %) of all subjects treated on an inpatient basis displayed elevated BP (>140/90 mmHg), while the remaining 47 % of patients showed normotensive readings (<140/90 mmHg) following admission. Moreover, 34 % of patients could be classified as therapy refractory. The main reasons for hospital admission were hypertension-related symptoms, including shortness of breath, dizziness, and headache (69 %). These patients were multi-morbid, with approximately 60 % displaying a secondary form of hypertension. Indeed, over half of the subjects showed renoparenchymatous forms of hypertension, and a large percentage of patients received hypertension-inducing drugs (32 %). Moreover, a high proportion of inpatients were treated with reserve antihypertensives, with the most commonly used drug being Moxonidin. CONCLUSION: The majority of hypertensive patients were hospitalized due to their clinical symptoms and not as a result of BP values alone. The high proportion of patients with secondary forms of hypertension or treated with BP-boosting medications was striking

The efficacy of antihypertensiye drugs in chronic intermittent hypoxia conditions

The authors would like to thank the Portuguese Fundacao para a Ciencia e a Tecnologia (FCT) and CEDOC (Chronic Diseases Research Centre, Lisbon, Portugal). Lucilia N. Diogo is supported by an FCT fellowship (SFRH/BD/48335/2008; PTDC/SAU-TOX/112264/2009).Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CRAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT.publishersversionpublishe