Comparison of continuous positive airway pressure and bosentan effect in mildly hypertensive patients with obstructive sleep apnoea: A randomized controlled pilot study.

BACKGROUND AND OBJECTIVE: Randomized controlled trials (RCT) have shown that continuous positive airway pressure (CPAP) has only limited impact on blood pressure (BP). Alternative strategies for obstructive sleep apnoea (OSA)-associated hypertension are therefore needed. Endothelin-1 has been demonstrated a key player in the deleterious cardiovascular consequences of OSA. In OSA, CPAP treatment has never been compared with endothelin receptor antagonist medications. Thus, we assessed the respective efficacy of CPAP and bosentan in reducing 24-h diastolic BP (DBP) in patients with OSA never treated by either therapy. METHODS: In a crossover pilot study, 16 mildly hypertensive patients (office systolic BP (SBP)/DBP: 142 ± 7/85 ± 8 mm Hg) with severe OSA (55 ± 8 years; body mass index, 29.6 ± 4.2 kg/m(2) ; apnoea-hypopnoea index, 40.8 ± 20.2/h) were randomized to either CPAP (n = 7) or bosentan (125 mg/day, n = 9) first for 4 weeks. After 2-weeks of washout, the second 4-week period consisted of the alternative treatment (in crossover). The primary outcome was the 24-h mean DBP change after treatment. RESULTS: In intention-to-treat analysis, the mean difference in 24-h DBP measurements between treatments was -3.1 (-6.9/0.7) mm Hg (median, 25th/75th percentiles) (P = 0.101) with bosentan having a greater effect. CONCLUSION: In this RCT, in mildly hypertensive patients with OSA, bosentan did not modify 24-h DBP but only reduced office BP suggesting that Endothelin-1 blockade does not play a major role in treatment of OSA-related hypertension.

Stress thallium-201/rest technetium-99m sequential dual-isotope high-speed myocardial perfusion imaging validation versus invasive coronary angiography.

BACKGROUND: Recent advances in nuclear myocardial perfusion imaging (MPI) have made it possible to develop a dual-isotope protocol for high-speed acquisition with image quality and radiation delivery comparable to that obtained with conventional single isotope protocols. So far, no study has compared dual-isotope high-speed MPI to invasive coronary angiography (ICA) in a large cohort using a Cadmium-zinc-telluride SPECT system. METHODS: Over a 1-year period (May 2011 to April 2012), 1366 patients underwent dual-isotope high-speed MPI. Patients with ICA within 3 months after dual-isotope high-speed MPI were included together with patients with a low likelihood of coronary artery disease (CAD) in order to assess normalcy rate. Global summed stress score (SSS) and summed rest score (SRS) were calculated, and ICA results were analyzed independently. The main end point was a patient-based assessment of the diagnostic performance of dual-isotope high-speed MPI in detecting or ruling out significant CAD (>70% reduction in lumen diameter). RESULTS: Inclusion criteria were fulfilled for 214 patients (143 men; age 60 ± 14 years; ICA, n = 104; low likelihood for CAD, n = 110). An exercise stress test was performed in 62% of patients and a pharmacological stress test was performed with either dipyridamole (32%) or dobutamine (6%). Average examination duration was 22.4 ± 4.5 minutes. Mean SSS, SRS, and SDS were 8.0 ± 4.9, 3.1 ± 4.3, and 5.0 ± 3.2, respectively. Prevalence of angiographic CAD was 75%. ICA detected stenosis in the left main trunk, left anterior descending artery, left circumflex artery, and right coronary artery in 4, 33, 31, and 42 patients, respectively. Sensitivity of dual-isotope high-speed MPI was 94%, normalcy rate was 92%, and accuracy was 83% for detecting CAD. CONCLUSION: Dual-isotope high-speed MPI is reliable at detecting or ruling out CAD. NCT01785589.

[Hypertension during obstructive sleep apnea syndrome]. / Hypertension artérielle au cours du syndrome d'apnées obstructives du sommeil.

Hypertension (HT) related to obstructive sleep apnea syndrome (OSAS) is one of the secondary forms of HT. It must be systematically evoked in hypertensive patient because the association "obesity, major snoring and excessive diurnal sleepiness" is fickle during OSAS. HT in apneic patient is more often diastolic, nocturnal, with a non-dipper profile. Moreover, OSAS is very frequently present during resistant hypertension. There are many mechanisms linking OSAS to HT. The main stimulus is intermittent hypoxia and the most important pathophysiological consequence is high sympathetic activity. After doing the diagnosis of OSAS, its treatment principally associated lifestyle changes with continuous positive airway pressure (CPAP). CPAP can significantly decrease blood pressure, especially if compliance to treatment is good and hypertension is resistant.

Potentially simple score of late gadolinium enhancement cardiac MR in acute myocarditis outcome.

PURPOSE: To determine the value of cardiac MRI for the monitoring and the prognosis of patients with acute myocarditis. Cardiac MRI plays an increasingly important role in the diagnosis of acute myocarditis. However, it is less established as a prognostic tool, which requires specific postprocessing of images. MATERIALS AND METHODS: In a prospective pilot study, we assessed the prognostic value of the evolution in a simplified visual quantitative score (SQS) of late gadolinium enhancement (LGE) between initial hospitalization and 3 months later. The prognostic value was assessed at 1 year using a combination of death, heart transplant, and confirmed recurrence as main outcome. RESULTS: Twenty-eight patients were included in this study. A significant correlation was found between LGE measured by SQS and planimetry (r = 0.95, P < 0.001). Intraobserver and interobserver reproducibilities were good for SQS (ICC = 0.95 [95% CI: 0.86 to 0.98], and 0.94 [95% CI: 0.84 to 0.98], respectively). At initial hospitalization, patient characteristics between the two groups were similar. Patients with stable or increased SQS suffered more frequently from clinical outcome events than patients with a decrease in SQS (P = 0.02). CONCLUSION: Monitoring of the evolution of LGE using a simple visual score is of interest to identify patients at risk of pejorative prognosis after acute myocarditis.

Is adrenal venous sampling mandatory before surgical decision in case of primary hyperaldosteronism?

BACKGROUND: Primary hyperaldosteronism (PHA) is a cause of secondary arterial hypertension potentially curable by laparoscopic unilateral adrenalectomy. We describe the follow-up of these patients according to their medical or surgical treatment. METHODS: We report a retrospective single-center study of 91 patients with PHA from 1998 to 2012. Treatment was guided by computed tomography (CT) scans. Preoperative adrenal vein sampling (AVS) was performed when the CT scan did not show single solitary unilateral nodules on the adrenal glands. During the follow-up, we considered hypertension to be cured in patients with normal blood pressure without antihypertensive medication (AM), and improvement was defined by a decrease in AM. RESULTS: A total of 28 patients received only AM. Of the 62 patients who underwent a unilateral adrenalectomy, 46 (74 %) had an adrenal adenoma, 14 (22 %) a hyperplasia, and the adrenal gland was normal in two cases. Hypertension was cured in 24 cases (38 %), and 28 patients (45 %) showed improvement with a reduction in AM. Predictive factors for a cure were gender, age, number of preoperative AMs, preoperative arterial systolic blood pressure, and plasma renin activity. All patients who presented with hypokalemia were cured postoperatively. We performed 38 AVS and nine of these patients were operated on based on the AVS findings, with an improvement of 100 % of arterial blood pressure after surgery. CONCLUSION: Laparoscopic unilateral adrenalectomy for PHA cured or improved hypertension in 84 % of patients. Preoperative AVS is mandatory for surgical decision making if the CT scan shows bilateral or no lesions associated with PHA.

Response to statin therapy in obstructive sleep apnea syndrome: a multicenter randomized controlled trial.

RATIONALE: Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. METHODS: This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters. RESULTS: 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m(2). In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (-0.29; 0.28), P = 0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: -6.34 mmHg (-12.68; -0.01), P = 0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. CONCLUSION: In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695.

Intermittent hypoxia-activated cyclooxygenase pathway: role in atherosclerosis.

Intermittent hypoxia, the main stimulus of obstructive sleep apnoea (OSA), induces inflammation, leading to early atherosclerosis. Whether the cyclooxygenase (COX) pathway contributes to intermittent hypoxia-induced atherosclerosis remains to be determined. We studied the effects of 8-weeks of intermittent hypoxia exposure on COX-pathway gene expression and atherosclerosis, and the influence of COX-1 inhibition by SC-560 on atherosclerosis progression in aortas of apolipoprotein E(-/-) mice. Urinary 11-dehydrothromboxane B2 (11-dTXB2) was assessed in 50 OSA subjects free of cardiovascular risk factor matched for age and body mass index with 25 controls, and 56 OSA with cardiovascular risk factor. Intermittent hypoxia significantly increased atherosclerotic lesion sizes, mRNA levels of COX-1 and thromboxane synthase (TXBS). Lesion sizes correlated to COX-1 (r = 0.654, p = 0.0003) and TXBS (r = 0.693, p<0.0001) mRNA levels. COX-1 inhibition reduced lesion progression in intermittent hypoxia mice only (p = 0.04). Urinary 11-dTXB2 was similar in OSA subjects free of cardiovascular risk factor and controls, but was increased by 13% (p = 0.007) in OSA subjects with cardiovascular risk factor compared with those without. Although OSA itself was not associated with increased urinary 11-dTXB2 concentration, the COX-1 pathway was activated in intermittent hypoxia-exposed mice and in OSA subjects presenting with cardiovascular risk factor, and may contribute to intermittent hypoxia-induced atherogenesis. COX-1 inhibition could be of clinical interest in the prevention of cardiovascular morbidity in OSA.

Profile of circulating cytokines: impact of OSA, obesity and acute cardiovascular events.

Obstructive sleep apnea (OSA) is inducing oxidative stress and consequently promotes systemic inflammation and cardiovascular morbidity. The respective impact of obesity, sleep apnea and acute cardiovascular events on the profile of inflammatory cytokines has not been extensively evaluated. We examined the profile of circulating cytokines in a case-control study comparing nonobese or obese patients with or without sleep apnea and with or without an acute cardiovascular event. Patients were assessed by sleep studies and inflammatory (hs-CRP, Leptin, RANTES, MCP1, IL6, IL8, TNF-α) and anti-inflammatory (adiponectin, IL1-Ra) cytokines profile. A cardiovascular phenotyping was performed including carotid intima-media thickness, pulse wave velocity and 24h blood pressure monitoring. In comparison with patients without sleep apnea or without comorbidities, patients with the combination of an acute cardiovascular event and pre-existing sleep apnea showed a higher burden of systemic inflammation with significant increase in serum levels of hs-CRP, IL1-Ra, IL-8, IL-6, TNF-α, Rantes and sICAM. Rantes and sICAM serum levels were independently associated with AHI after an acute cardiovascular event. Serum levels of different inflammatory markers were significantly increased in patients with the combination of sleep apnea and an acute cardiovascular event. Since these biomarkers could be associated with worsened cardiovascular outcome, diagnosing and treating associated sleep apnea is potentially important in patients after an acute cardiovascular event.

[Management of hypertension recorded as at least 180/110 mmHg]. / Prise en charge d'une hypertensìon artérielle supérieure ou égale a 180/110 mmHg.

Stage 3 hypertension (severe) is far from rare. It may be part of a previous hypertension condition which is difficult to control, or occur more acutely, in which case it will be harder for the patient to bear. When it is symptomatic and a fortiorione or more organs targeted by hypertension are affected, management must be fast and appropriate. It may take the form of a hypertensive urgency, in which case the investigations and treatment usually take place in outpatients, with oral treatment. it may also be a hypertensive emergency for which treatment involves hospitalization in an intensive care unit with intravenous anti-hypertensive treatment. A reduction in blood pressure must be obtained rapidly but not suddenly; it must be more or less significant depending on the clinical situation, and also progressive.

Leukotriene B4 pathway activation and atherosclerosis in obstructive sleep apnea.

Leukotriene B(4) (LTB(4)) production increases in obstructive sleep apnea syndrome (OSA) and is linked to early vascular remodeling, the mechanism of which is unknown. The objective of this study was to to determine the molecular mechanisms of LTB(4) pathway activation in polymorphonuclear cells (PMNs) and early vascular remodeling in OSA and the specific contribution of intermittent hypoxia (IH). PMNs were isolated from 120 OSA patients and 33 healthy subjects and used for measurements of LTB(4) production, determination of mRNA and protein expression levels, or exposed for four cycles of in vitro IH. PMNs derived from OSA patients exhibited increased LTB(4) production, for which apnea-hypopnea index was an independent predictor (P=0.042). 5-Lipoxygenase-activating protein (FLAP) mRNA and protein increased significantly in PMNs from OSA patients versus controls and were associated with carotid luminal diameter and intima-media thickness. LTB(4) (10 ng/ml) increased IL-6 (P=0.006) and MCP-1 (P=0.002) production in OSA patient monocytes. In vitro exposure of PMNs from controls to IH enhanced FLAP mRNA levels (P= 0.027) and induced a 2.7-fold increase (P=0.028) in LTB(4) secretion compared with PMNs exposed to normoxia. In conclusion, upregulation of FLAP in PMNs in response to IH may participate in early vascular remodeling in OSA patients, suggesting FLAP as a potential therapeutic target for the cardiovascular morbidity associated with OSA.

The inflammatory preatherosclerotic remodeling induced by intermittent hypoxia is attenuated by RANTES/CCL5 inhibition.

RATIONALE: The highly prevalent obstructive sleep apnea syndrome (OSA) with its main component intermittent hypoxia (IH) is a risk factor for cardiovascular mortality. The poor knowledge of its pathophysiology has limited the development of specific treatments, whereas the gold standard treatment, continuous positive airway pressure, may not fully reverse the chronic consequences of OSA and has limited acceptance in some patients. OBJECTIVES: To examine the contribution of IH-induced inflammation to the cardiovascular complications of OSA. METHODS: We investigated systemic and vascular inflammatory changes in C57BL6 mice exposed to IH (21-5% Fi(O(2)), 60-s cycle) or normoxia 8 hours per day up to 14 days. Vascular alterations were reassessed in mice treated with a blocking antibody of regulated upon activation, normal T-cell expressed and secreted (RANTES)/CC chemokine ligand 5 (CCL5) signaling pathway, or with the IgG isotype control throughout the IH exposure. MEASUREMENTS AND MAIN RESULTS: IH induced systemic inflammation combining increased splenic lymphocyte proliferation and chemokine expression, with early and predominant RANTES/CCL5 alterations, and enhanced splenocyte migration toward RANTES/CCL5. IH also induced structural and inflammatory vascular alterations. Leukocyte-endothelium adhesive interactions were increased, attested by leukocyte rolling and intercellular adhesion molecule-1 expression in mesenteric vessels. Aortas had increased intima-media thickness with elastic fiber alterations, mucoid depositions, nuclear factor-κB-p50 and intercellular adhesion molecule-1 overexpression, hypertrophy of smooth-muscle cells overexpressing RANTES/CCL5, and adventitial-periadventitial T-lymphocyte infiltration. RANTES/CCL5 neutralization prevented both intima-media thickening and inflammatory alterations, independently of the IH-associated proatherogenic dyslipidemia. CONCLUSIONS: Inflammation is a determinant mechanism for IH-induced preatherosclerotic remodeling involving RANTES/CCL5, a key chemokine in atherogenesis. Characterization of the inflammatory response could allow identifying at-risk patients for complications, and its pharmacologic manipulation may represent a potential complementary treatment of sleep apnea consequences.

The IDEAL study : towards personalized drug treatment of hypertension.

OBJECTIVE: To identify markers (phenotypic, genetic, or environmental) of blood pressure (BP) response profiles to angiotensin converting enzyme inhibitors (ACEIs) and diuretics. METHODS: IDEAL was a crossover (two active and two wash out phases), double-blind, placebo-controlled trial. Eligible patients were untreated hypertensive, aged 25 to 70. After two visits, patients were randomized to one of four sequences. The main outcome was BP differences between the active treatment and placebo. RESULTS: One hundred and twenty-four patients were randomised: mean age 53, men 65%, family history of hypertension 60%. Average BP fall at each visit before randomisation was about 2% of the initial level reflecting both a regression to the mean and a placebo effect. CONCLUSION: The results are expected to improve knowledge in drug's mechanisms of action and pathophysiology of hypertension, and to help in personalizing treatment. The estimation of BP responses to each drug in standardized conditions provided a benefit to each participant.

Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea.

RATIONALE: Randomized controlled trials (RCTs) have shown that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) reduces blood pressure (BP). CPAP treatment has never been compared with antihypertensive medications in an RCT. OBJECTIVES: To assess the respective efficacy of CPAP and valsartan in reducing BP in hypertensive patients with OSA never treated for either condition. METHODS: In this 8-week randomized controlled crossover trial, 23 hypertensive patients (office systolic BP/diastolic BP: 155 ± 14/102 ± 11 mm Hg) with OSA (age, 57 ± 8 yr; body mass index, 28 ± 5 kg/m(2); apnea-hypopnea index, 29 ± 18/h) were randomized first to either CPAP or valsartan (160 mg). The second 8-week period consisted of the alternative treatment (crossover) after a 4-week washout period. MEASUREMENTS AND MAIN RESULTS: Office BP and 24-hour BP were measured before and at the end of the two active treatment periods. Twenty-four-hour mean BP was the primary outcome variable. There was an overall significant difference in 24-hour mean BP between treatments: the change in 24-hour mean BP was -2.1 ± 4.9 mm Hg (P < 0.01) with CPAP, and -9.1 ± 7.2 mm Hg with valsartan (P < 0.001), with a difference of -7.0 mm Hg (95% confidence interval, -10.9 to -3.1 mm Hg; P < 0.001). The difference was significant not only during daytime but also during nighttime: the change in nighttime mean BP with CPAP was -1.3 ± 4.6 mm Hg (not significant), and -7.4 ± 8.4 mm Hg with valsartan (P < 0.001), with a difference of -6.1 mm Hg (P < 0.05) (95% confidence interval, -10.8 to -1.4 mm Hg). CONCLUSIONS: In an RCT, although the BP decrease was significant with CPAP treatment, valsartan induced a fourfold higher decrease in mean 24-hour BP than CPAP in untreated hypertensive patients with OSA. Clinical trial registered with www.clinicaltrials.gov (NCT00409487).

Choroidal blood-flow responses to hyperoxia and hypercapnia in men with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) impacts on macrovasculature and autonomic function and may therefore interfere with ocular microvascular regulation. We hypothesized that choroidal vascular reactivity to hyperoxia and hypercapnia was altered in patients with OSA compared with matched control subjects and would improve after treatment with continuous positive airway pressure (CPAP). METHODS: Sixteen healthy men were matched 1:1 for body mass index, sex, and age with 16 men with newly diagnosed OSA without comorbidities. Subjects underwent sleep studies, 24-hour blood pressure monitoring, arterial stiffness measurements, and cardiac and carotid echography. Overall, patients were middle-aged, lean, and otherwise healthy except for having OSA with a limited amount of desaturation, with, at most, subclinical lesions of the cardiovascular system, stage 1 hypertension, or both. Choroidal laser Doppler flowmetry provides a unique opportunity to assess microvascular function by measuring velocity, (ChBVel), volume (ChBVol), and relative subfoveal choroidal blood flow (ChBF). Vascular choroidal reactivity was studied during hyperoxia and hypercapnia (8% CO2) challenges before and after treatment with nasal CPAP. RESULTS: Patients with OSA and control subjects exhibited similar choroidal reactivity during hyperoxia (stability of choroidal blood flow) and hypercapnia (significant increases in ChBVel of 13.5% and in ChBF of 16%). Choroidal vasoreactivity to CO2 was positively associated with arterial stiffness in patients with OSA. Gas choroidal vasoreactivity was unchanged after 6 to 9 months of CPAP treatment. CONCLUSION: This study showed unimpaired choroidal vascular reactivity in otherwise healthy men with OSA. This suggests that patients with OSA, without comorbidities, have long-term adaptive mechanisms active in ocular microcirculation.

Hemorrhagic tamponade due to cardiac angiosarcoma.

Prognosis of angiosarcoma, the most common primary malignant cardiac tumor, is very poor. An early detection and treatment may extend survival beyond one year. Newer imaging modalities, including magnetic resonance imaging (MRI), play an important role in the evaluation of cardiac masses. The case of a man admitted to the emergency room for a cardiac tamponade is reported. Thoracic computed tomography and MRI diagnosed a pericardial tumor, for which surgical biopsy revealed an angiosarcoma. Chemotherapy was started, and the patient survived for 28 months. Etiologies of hemorrhagic tamponades are discussed, as well as treatment of cardiac angiosarcoma.

Increased urinary leukotriene E4 excretion in obstructive sleep apnea: effects of obesity and hypoxia.

BACKGROUND: Low-grade inflammation may potentially explain the relationship between obstructive sleep apnea syndrome (OSA) and cardiovascular events. However, the respective contribution of intermittent hypoxia and confounders, such as obesity, is still debated. OBJECTIVES: To monitor urinary leukotriene E(4) (U-LTE(4)), a validated marker of proinflammatory cysteinyl leukotriene production, in OSA; to determine the influence of obesity and other confounders on U-LTE(4) concentrations; to examine the mechanisms involved through transcriptional profiling of the leukotriene pathway in peripheral blood mononuclear cells (PBMCs); and to investigate the effect of continuous positive air pressure (CPAP) on U-LTE(4) concentrations. METHODS: We measured U-LTE(4) by liquid chromatography-tandem mass spectrometry. RESULTS: The U-LTE(4) concentrations were increased (P = .019) in 40 nonobese patients with OSA carefully matched for age, sex, and body mass index (BMI) to 25 control subjects, and correlated (r = 0.0312; P = .017) to the percentage of time spent with mean oxygen saturation (SaO(2)) less than 90%. In a larger cohort of patients with OSA (n = 72), U-LTE(4) increased as a function of BMI (r = 0.445; P = .0002). In those patients, the expression levels of 5-lipoxygenase activating protein mRNA in mononuclear cells exhibited a similar pattern. A stepwise multiple linear regression analysis performed in this cohort identified BMI (P = .001; regression coefficient, 3.33) and percentage of time spent with SaO(2) <90% (P = .001; regression coefficient, 1.01) as independent predictors of U-LTE(4) concentrations. Compared with baseline, CPAP reduced by 22% (P = .006) U-LTE(4) concentrations only in patients with OSA with normal BMI. CONCLUSION: Obesity, and to a lesser extent hypoxia severity, are determinant of U-LTE(4) production in patients with OSA.

A rare cause of complicated hypertension: urinary bladder paraganglioma.

After a subarachnoid hemorrhage, a 35-year-old patient developed paroxystic hypertension accompanied by typical symptoms. These symptoms occurred exclusively after urination. A urinary bladder paraganglioma was discovered using iodine-123 metaiodobenzylguanidine (I-123 MIBG) scintigraphy and magnetic resonance imaging (MRI) after the detection of an abnormally elevated plasma metanephrine measurement. A partial cystectomy was performed which cured the symptoms. Paragangliomas, defined by their extra-adrenal localization, have slightly different characteristics than pheochromocytomas, leading to specific care and follow up.

EVAluation of the prognostic value of BARoreflex sensitivity in hypertensive patients: the EVABAR study.

AIMS: The prognostic value of baroreflex sensitivity in hypertensive patients has not much been studied. METHOD: A cohort of 451 hypertensive patients without cardiovascular history was studied for an average of 6.2 +/- 2.8 years follow-up. Each patient had a baroreflex sensitivity measurement by the sequence method, which is represented by the slope of up-sequences (systolic blood pressure+/pulse interval+) and down-sequences (systolic blood pressure-/pulse interval-) of spontaneous fluctuations in systolic blood pressure and pulse interval. RESULTS: During the follow-up, there were 20 deaths from any cause and 30 patients presented a major adverse cardiovascular event. Deaths and major adverse cardiovascular events were associated with a reduction in baroreflex sensitivity (systolic blood pressure+/pulse interval+ and systolic blood pressure-/pulse interval-). In multivariate analysis, the reduction in baroreflex sensitivity systolic blood pressure+/pulse interval+ was associated with an increased risk of deaths from any cause (Odds ratio 1.23; 95% confidence interval 1.02-1.67, P = 0.04). A baroreflex sensitivity systolic blood pressure+/pulse interval+ under 4.5 ms/mmHg was associated with a 2.5-increased relative risk of major adverse cardiovascular event (95% confidence interval 1.11-5.93, P = 0.03). However, multivariate analysis showed that baroreflex sensitivity systolic blood pressure-/pulse interval- was not associated either with death or major adverse cardiovascular events. CONCLUSIONS: Reduction in baroreflex sensitivity marked by a reduction in vagal reflexes is an independent marker of the risk of mortality and major adverse cardiovascular events in hypertensive patients.