Human hypertension: observations on autonomic nervous system control mechanisms and clinical associations

Introduction: Sympathetic nerve activity (SNA) undergoes physiological modulation by respiration but it remains unclear whether this process is altered by age and hypertension. Aims: To establish relationship between respiration and neural regulation of the cardiovascular system in aging and hypertension. Methods: Multiunit muscle SNA, BP, respiratory parameters and heart rate were recorded at rest in young and older healthy men and hypertensive patients, then repeated in hypertensive group after acute and long-term device-guided slow deep-breathing (SDB) training. Results: Muscle SNA was higher in older subjects but showed similar modulation by respiration in both age groups. In young acute SDB reduced SNA, with no effect on sympathetic and cardiac baroreflex sensitivity. The sympathoinhibition was not related to changes in baroreflex sensitivity, but it reflected increases in lung inflation afferent input and/or reduction in central respiratory-sympathetic coupling. Long-term SDB training inhibited muscle SNA in hypertensive patients and led to acute increase in heart rate variability and longer-term BP reduction. There were no changes in baroreflex sensitivity, cardiac structure/function or arterial stiffness in response to SDB training. Conclusions: The study provides new mechanistic insights into sympathetic regulatory pathways in hypertension and aging, which may help to establish anti-hypertensive strategy based on respiratory modulation

Premature cardiac ageing in South Asian compared to Afro-Caribbean subjects in a community based screening study:cardiac ageing in South Asians

People of South Asian (SAs) and African Caribbean (AC) origin have increased cardiovascular morbidity, but underlying mechanisms are poorly understood. Ageing is the key predictor of deterioration in diastolic function, which can be assessed by echocardiography using E/e’ ratio as a surrogate of left ventricular (LV) filling pressure. The study aimed to assess a possibility of premature cardiac ageing in SA and AC subjects. We studied 4540 subjects: 2880 SA and 1660 AC subjects. All participants underwent detailed echocardiography, including LV ejection fraction (LVEF), average septal-lateral E/e’, LV mass index (LVMI). When compared to ACs, SAs were younger, with lower mean LVMI, systolic BP, diastolic BP and BMI, as well as a lower prevalence of hypertension and smoking (p ≤0.001 for all). In a multivariate linear regression model including age, gender, ethnicity, BP, heart rate, BMI, waist circumference, LVMI, history of smoking, hypertension, coronary artery disease, diabetes, medications, SA origin was independently associated with higher E/e’ (regression coefficient ± standard error -0.66±0.10, p<0.001, adjusted R-squared for the model 0.21, p<0.001). Furthermore, SAs had significantly accelerated age-dependent increase in E/e’ compared to ACs. On multivariable Cox regression analysis without adjustment for E/e’ SA ethnicity was independently predictive of mortality (p=0.04). After additional adjustment for E/e’ the ethnicity lost its significance value, whilst E/e’ was independently predictive of higher risk of death (p=0.008). Premature cardiac ageing is evident in SAs and may contribute to high cardiovascular morbidity in this ethnic group, compared to ACs

Dynamic changes of monocytes subsets predict major adverse cardiovascular events and left ventricular function after STEMI.

We explored how dynamic changes in monocyte subset counts (as opposed to static values to specific time points), and their phagocytic and NFκB activity relate to major adverse cardiovascular events (MACE) and left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI). Changes in counts, phagocytic activity and intracellular levels of inhibitory κB kinase β (IKKβ) (a marker of NFκB activity) of monocyte subsets (CD14++CD16-CCR2+ [Mon1], CD14++CD16+CCR2+ [Mon2] and CD14+CD16++CCR2- [Mon3]) were measured by flow cytometry in patients with STEMI at baseline, and again after one week, two weeks, and one month. LVEF was measured by echocardiography at baseline and six months after STEMI. Baseline data included 245 patients (mean ± SD age 60 ± 12 years; 22% female), who were followed for a median of 46 (19-61) months. Multivariate Cox regression demonstrated that more prominent dynamic reduction in Mon2 by week 1 (n = 37) was independently associated with fewer MACE (HR 0.06, 95% CI 0.01-0.55, p = 0.01). Also, less prominent reduction in Mon2 at month 1 (n = 24) was independently predictive of 6-month LVEF. None of the other dynamic changes in monocyte subsets were associated with changes in survival from MACE. Neither phagocytic activity nor IKKβ were associated with survival for each monocyte subset. We showed how distinct pattern of dynamic changes in Mon2 are related to both MACE risk and recovery of cardiac contractility. Further research is needed to understand the mechanism of the monocyte effect and possibilities of their pharmacological manipulation

Clinical features and prognosis in patients with atrial fibrillation and prior stroke: Comparing the Fushimi and Darlington AF Registries

Background: Ethnic differences in clinical characteristics, stroke risk profiles and outcomes among atrial fibrillation (AF) patients may exist. We therefore compared AF patients with previous stroke from Japan and the United Kingdom (UK). Methods: We compared clinical characteristics, stroke risk and outcomes among AF patients from the Fushimi AF registry who had experienced a previous stroke (Japan; n = 688; 19.7%) and the Darlington AF registry (UK; n = 428; 19.0%). Results: AF patients with previous stroke in Fushimi were significantly younger (76.8 and 79.6 years of age in Fushimi and Darlington; p < 0.01) with a lower proportion of females (37.4% vs. 45.1%; p = 0.01) than those from Darlington. Although the CHA2DS2-VASc score was lower in AF patients in Fushimi than those in Darlington (5.18 vs. 5.57; p < 0.01), oral anticoagulation (OAC) was prescribed significantly more frequently in Fushimi (68.3%) than Darlington (61.7%) (p = 0.02). Multivariate logistic regression analysis showed that Japanese ethnicity was associated with a significantly decreased risk of recurrent stroke (OR 0.59. 95% CI 0.36–0.97; p = 0.04) but a significantly increased risk of all-cause mortality (OR 1.76, 95% CI 1.18–2.66; p < 0.01) in AF patients with previous stroke. Conclusions: AF patients with previous stroke in the UK were at higher risk of recurrent stroke compared to Japanese patients, but OAC was utilised less frequently. There was a lower risk of recurrent stroke in the secondary prevention cohort from the Fushimi registry, but an increased risk of all-cause mortality

Ventricular-arterial coupling in obstructive sleep apnea

Arterial elastance (Ea) and systolic elastance are important parameters determining effective functional interaction of heart and vessels. The aims of this study were to (1) compare arterial (arterial elastance index [EaI]) and ventricular (end-systolic elastance [Ees] and end-diastolic elastance [Eed]) elastance in subjects with obstructive sleep apnea (OSA) and patients with treated ‘high-risk’ hypertension (HHT) and (2) test whether these parameters in OSA patients can be improved by continuous positive airway pressure (CPAP) therapy. Echocardiographic parameters of cardiac and vascular stiffness (EaI, Ees, and Eed) were quantified in 28 patients with OSA (mean [standard deviation], age 51 [11] years; 79% male) and 28 treated subjects with HHT (mean [standard deviation], age 48 [12] years; 61% male). Twenty-three OSA patients were treated with CPAP for median of 26 weeks. Ea was calculated from stroke volume and systolic BP and adjusted by body area (EaI). Both study groups had preserved and comparable left ventricle contractility. There was no significant differences in EaI (P = .94), Ees (P = .5), Eed (P = .63), and arterial-ventricular interaction (P = .62) between OSA and HHT groups. After CPAP therapy, there was a significant reduction in EaI (paired t test, P = .013) and arterial-ventricular interaction (paired t test, P = .004). Ees (P = .17) and Eed (P = .66) parameters did not change significantly. OSA and HHT patients have similar parameters of elastance and ventricular-arterial coupling. CPAP treatment in OSA patients significantly improved ventricular-arterial coupling

Rivaroxaban Versus Dabigatran or Warfarin in Real-World Studies of Stroke Prevention in Atrial Fibrillation

Background and Purpose— This study was designed to evaluate the effectiveness and safety of rivaroxaban in real-world practice compared with effectiveness and safety of dabigatran or warfarin for stroke prevention in atrial fibrillation through meta-analyzing observational studies. Methods— Seventeen studies were included after searching in PubMed for studies reporting the comparative effectiveness and safety of rivaroxaban versus dabigatran (n=3), rivaroxaban versus Warfarin (n=11), or both (n=3) for stroke prevention in atrial fibrillation. Results— Overall, the risks of stroke/systematic thromboembolism with rivaroxaban were similar when compared with those with dabigatran (stroke/thromboembolism: hazard ratio, 1.02; 95% confidence interval, 0.91–1.13; I2=70.2%, N=5), but were significantly reduced when compared with those with warfarin (hazard ratio, 0.75; 95% confidence interval, 0.64–0.85; I2=45.1%, N=9). Major bleeding risk was significantly higher with rivaroxaban than with dabigatran (hazard ratio, 1.38; 95% confidence interval, 1.27–1.49; I2=26.1%, N=5), but similar to that with warfarin (hazard ratio, 0.99; 95% confidence interval, 0.91–1.07; I2=0.0%, N=6). Rivaroxaban was associated with increased all-cause mortality and gastrointestinal bleeding, but similar risk of acute myocardial infarction and intracranial hemorrhage when compared with dabigatran. When compared with warfarin, rivaroxaban was associated with similar risk of any bleeding, mortality, and acute myocardial infarction, but a higher risk of gastrointestinal bleeding and lower risk of intracranial hemorrhage. Conclusions— In this systematic review and meta-analysis, rivaroxaban was as effective as dabigatran, but was more effective than warfarin for the prevention of stroke/thromboembolism in atrial fibrillation patients. Major bleeding risk was significantly higher with rivaroxaban than with dabigatran, as was all-cause mortality and gastrointestinal bleeding. Rivaroxaban was comparable to warfarin for major bleeding, with an increased risk in gastrointestinal bleeding and decreased risk of intracranial hemorrhage