OBJECTIVE:Studies addressing the association between a reduced drop of heart rate (HR) at night with subclinical organ damage and cardiovascular events in the general population are scanty. We ...evaluated this issue in subjects enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study.
DESIGN AND METHOD:At entry 2,021 subjects underwent diagnostic tests including laboratory investigations, 24-h ambulatory blood pressure (BP) monitoring and echocardiography. Participants were followed from the initial medical visit for a time interval of 148 ± 27 months. To explore the association of circadian HR rhythm and outcomes participants were classified in the primary analysis according to quartiles of nocturnal HR decrease. In secondary analyses the population was also classified according non-dipping nocturnal HR (defined as a drop in average HR at night lower than 10% compared to day-time values) and next in four categories(1) BP/HR dipper, 2) BP/HR non dipper, 3) HR dipper/BP non dipper, 4) HR non dipper/BP dipper).
RESULTS:A flattened circadian HR rhythm (i.e. lowest quartile of night-time HR dip) was independently associated to left atrial (LA) enlargement, but not to left ventricular hypertrophy; moreover, it was predictive of fatal and non-fatal cardiovascular events, independently of several confounders (hazard ratio 1.8, CI1.13–2.86, p < 0.01 vs highest quartile).
CONCLUSIONS:A blunted dipping of nocturnal HR is associated to preclinical cardiac damage in terms of LA enlargement and is predictive cardiovascular morbidity and mortality in the general population.
OBJECTIVE:The association between pre-hypertension (pre-HTN) and subclinical cardiac organ damage is not well defined. We performed a systematic meta-analysis of echocardiographic studies in order to ...provide a comprehensive information on cardiac structural and functional changes in untreated pre-HTN subjects.
DESIGN AND METHOD:Studies were identified by crossing the following search termspre-hypertension, high normal blood pressure, heart, left ventricular hypertrophy, left ventricular function, diastolic function, left atrial size, aortic root size, echocardiography.
RESULTS:A total 73,556 subjects (44,170 normotensive, 17,314 pre-HTN, and 12,072 HTN individuals) of both genders were included in 20 studies. Left ventricular (LV) mass index was greater in pre-HTN than in normotensives (standard means difference SMD0.32 ± 0.07, p < 0.001). Mitral E/A ratio was lower (SMD−0.34. ± 0.05,p < 0.001), E/e’ ratio (SMD0.26 ± 0.02, p < 0.001) and left atrium (LA) diameter higher (SMD0.55 ± 0.02, p < 0.001) in pre-HTN than in normotensive counterparts. HTN subjects showed a greater LV mass index (SMD0.27 ± 0.03, p < 0.001), reduced E/A (SMD−0.38 ± 0.08, p < 0.001), increased E/e’ ratio (SMD0.38 ± 0.09, p < 0.001), and LA diameter (SMD0.31 ± 0.12, p < 0.001) than pre-HTN subjects
CONCLUSIONS:Our meta-analysis shows that alterations in cardiac structure and function in pre-HTN subjects are intermediate between normotensive and HTN individuals. These findings reinforce the view that pre-HTN should not be longer considered a benign entity.
OBJECTIVE:Clinical trials have shown initial combination therapy to be more effective on blood pressure (BP) control than initial monotherapy but few studies examined the question in a large primary ...care database. The main objective of this study was to evaluate relative effectiveness on BP of an initial two-drug therapy compared to monotherapy in hypertension (HT).
DESIGN AND METHOD:In the UK Clinical Practice Research Datalink with hospitalisation and mortality data linkage, we identified a cohort of adults with uncontrolled HT and initiating one or two antihypertensive drug class(es) (among ACEIs, ARBs, CCB, BB, thiazide-like diuretics) between 2006 and 2014, with follow-up until February 2016. New users of 2-drugs and monotherapy were matched 1:2 using a propensity score. Exposure was defined as intention-to-treat (ITT) or as treated (AT), i.e. until first regimen change. Primary and secondary endpoints were respectively BP control and serious cardiovascular event (SCE). Analyses in planned subgroups, according to HT severity or most frequent classes of drugs (ACEi, CCB) used specific propensity scores.
RESULTS:Among 54,523 eligible hypertensive patients included, 3,256 patients were initiated on 2 drugs of which 2,807 (86.2%) were matched to 5,614 monotherapy new users (mean SBP/DBP 164.6/94.8 mm Hg). During a mean follow-up (ITT) of 4.6 years, mean exposure duration (AT) was 12.7 months, with 76.5% patients changing initial regimen. In the AT analysis, use of 2 drugs was associated with 17% increased BP control in all hypertensive patients (HR 95%CI1.17 1.09–1.26), increasing to 28% in patients with grade 2–3 HT (1.28 1.17–1.41), and 27% in patients with ACEi+CCB (1.27 1.08–1.49). A positive association was also observed in the ITT analysis of all hypertensive patients (1.08 1.03–1.13) or those with grade 2–3 HT (1.10 1.03–1.18). For SCE, overall no significant association with 2-drug therapy was found.
CONCLUSIONS:In line with UK guidelines, only a small fraction of hypertensive patients used two drugs in combination as initial therapy. This large population-based cohort study supports the evidence of greater effectiveness of 2-drug therapy for BP control, while additional data would be required for SCE.
OBJECTIVE:Exaggerated blood pressure (BP) response (EBPR) during exercise predicts future hypertension and cardiovascular events in different patients groups and general population. However, the ...clinical and prognostic implications of EBPR during exercise treadmill test (ETT) in patients with aortic stenosis (AS) have not been tested before.
DESIGN AND METHOD:We retrospectively assessed 316 patients with moderate (66%) or severe (34%) asymptomatic AS (age 65 ± 12 years) who underwent echocardiography and modified Bruce ETT at a specialist valve clinic. EBPR was defined as peak systolic BP 190mmHg or above.
RESULTS:The prevalence of EBPR was 22%. There was no difference in exercise duration, metabolic equivalents or severity of AS between patients with normal BP response and EBPR (all p = NS). Patients with EBPR were more likely to have hypertension, higher pre-test systolic BP, left ventricular (LV) ejection fraction and increased LV mass (all p < 0.05) (Table). A total of 264 events occurred during a mean follow up period of 34.9 ± 35.1 months. 234 patients reached an indication for aortic valve replacement (AVR), 75% in patients with normal BP response vs. 73% in patients with EBPR, p = NS). Among 30 (9%) deaths, 9.4% occurred in patients with normal BP response vs. 8.1% in EBPR group, p = NS). In univariate Cox regression analysis, the presence of EBPR was neither associated with all-cause mortality {HR 0.89, 95%CI 0.33–2.36, p = 0.814} nor AVR {HR 0.96, 95%CI 0.69–1.33, p = 0.785}.
CONCLUSIONS:EBPR during treadmill exercise test in moderate to severe asymptomatic AS patients was strongly associated with hypertension and increased LV mass, but could not predict adverse outcomes.
The benefits of reducing blood pressure on the risks of major cardiovascular disease are well established, but uncertainty remains about the comparative effects of different blood-pressure-lowering ...regimens. We aimed to estimate effects of strategies based on different drug classes (angiotensin-converting-enzyme ACE inhibitors, calcium antagonists, angiotensin-receptor blockers ARBs, and diuretics or β blockers) or those targeting different blood pressure goals, on the risks of major cardiovascular events and death.
We did seven sets of prospectively-designed overviews with data from 29 randomised trials (n=162 341). The trial eligibility criteria, primary outcomes, and main hypotheses were specified before the result of any contributing trial was known.
In placebo-controlled trials the relative risks of total major cardiovascular events were reduced by regimens based on ACE inhibitors (22%; 95% CI 17–27) or calcium antagonists (18%; 5–29). Greater risk reductions were produced by regimens that targeted lower blood pressure goals (15%; 5–24). ARB-based regimens reduced the risks of total major cardiovascular events (10%; 4–17) compared with control regimens. There were no significant differences in total major cardiovascular events between regimens based on ACE inhibitors, calcium antagonists, or diuretics or β blockers, although ACE-inhibitor-based regimens reduced blood pressure less. There was evidence of some differences between active regimens in their effects on cause-specific outcomes. For every outcome other than heart failure, the difference between randomised groups in achieved blood pressure reduction was directly related to the observed difference in risk.
Treatment with any commonly-used regimen reduces the risk of total major cardiovascular events, and larger reductions in blood pressure produce larger reductions in risk.
OBJECTIVE:Activity of the sympathetic nervous system (SNS) is increased in hypertensive patients with chronic kidney disease (CKD). In this updated version, we tested the hypothesis whether ...hypertensive patients with CKD enrolled in the Global Symplicity Registry (GSR) showed different responses in blood pressure (BP) reduction in the short- and long-term follow-up.
DESIGN AND METHOD:The GSR (NCT 01534299) is a prospective, open-label, international, multicentre observational study for assessment of safety and effectiveness of renal denervation (RDN) among real-world patients treated with the Symplicity™ RDN system (Medtronic, Santa Rosa, CA, USA). Inclusion criteria are age >= 18 years and eligibility for RDN. Office and 24-h ambulatory BP were assessed at pre-specified time-points (12, 24 and 36 months). For the current updated analyses, enrolled patients (N = 1980) were stratified based on baseline estimated glomerular filtration rate in <60 vs. >= 60 ml/min/1.73m2 into with (N = 475) and without (N = 1505) CKD groups.
RESULTS:Patients with CKD were significantly older (p < 0.0001) and more likely to be female (p = 0.0027) compared to patients without CKD. At baseline office systolic BP was lower (162.4 ± 26 vs. 165.8 ± 24 mmHg, p = 0.0113), whereas there was no difference in baseline 24-h ambulatory systolic BP (153.6 ± 19 vs. 153.7 ± 18 mmHg, p = 0.9162), in patients with, compared to without CKD. In patients with and without CKD, office as well as 24-h ambulatory BP were significantly reduced after RDN compared to baseline values at all time-points (all p < 0.001). There was a greater office systolic BP reduction in favor of patients without compared to with CKD, whereas no difference in 24-h ambulatory systolic BP reduction after RDN, even after adjustment (Table), was observed.(Figure is included in full-text article.)
CONCLUSIONS:After adjustment for baseline data, BP reduction after RDN showed a disparate response pattern in office and 24-h ambulatory BP reductions in patients with CKD. Data needs to be confirmed by a rigorously conducted, prospective, double-blind, sham-controlled study.
Previous studies have shown that alterations in vascular, metabolic, inflammatory and haemocoagulative functions characterise the metabolic syndrome. Whether this is also the case for sympathetic ...function is not clear. We therefore aimed to clarify this issue and to determine whether metabolic or reflex mechanisms might be responsible for the possible adrenergic dysfunction.
In 43 healthy control subjects (age 48.2+/-1.0 years, mean+/-SEM) and in 48 untreated age-matched subjects with metabolic syndrome (National Cholesterol Education Program's Adult Treatment Panel III Report criteria) we measured, along with anthropometric and metabolic variables, blood pressure (Finapres), heart rate (ECG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation (vasoactive drug infusion technique).
Compared with control subjects, subjects with metabolic syndrome had higher BMI, waist circumference, blood pressure, cholesterol, triglycerides, insulin and homeostasis model assessment (HOMA) index values but lower HDL cholesterol values. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in control subjects (61.1+/-2.6 vs 43.8+/-2.8 bursts/100 heartbeats, p<0.01), the presence of sympathetic activation also being detectable when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic correlated directly and significantly with waist circumference (r=0.46, p<0.001) and HOMA index (r=0.49, p<0.001) and was inversely related to baroreflex sensitivity (r=-0.44, p<0.001), which was impaired in the metabolic syndrome.
These data provide evidence that the metabolic syndrome is characterised by sympathetic activation and that this abnormality (1) is also detectable when blood pressure is normal and (2) depends on insulin resistance as well as on reflex alterations.
Background
Resting heart rate (RHR) is associated with cardiovascular disease outcomes in high‐risk patients. It is not known whether RHR is predictive of renal outcomes such as albuminuria, ...end‐stage renal disease (ESRD) or doubling of creatinine. We evaluated whether RHR could predict renal endpoints in patients at a high risk of cardiovascular disease. We also tested the effects of RHR at different levels of systolic blood pressure (SBP).
Methods
We analysed data from 28 757 patients in the ONTARGET and TRANSCEND trials. RHR and SBP were available for a mean of 4.9 ± 0.4 visits (range 3–5) within the first 2 years of the studies. Albuminuria was determined at baseline, at 2 years and at study end.
Results
Mean RHR was predictive of incident micro‐albuminuria hazard ratio (HR) for RHR ≥80 vs. <60 beats min−1 1.49, 95% confidence interval (CI) 1.29–1.71, P < 0.0001, incident macro‐albuminuria (HR 1.84, 95% CI 1.39–2.42, P < 0.0001), doubling of creatinine (HR 1.47, 95% CI 1.00–2.17, P = 0.050) and ESRD (HR 1.78, 95% CI 1.00–3.16, P = 0.050), and the combined renal end‐point (HR 1.51, 95% CI 1.32–1.74, P < 0.0001). Associations were robust at SBPs from <120 to ≥150 mmHg, with the lowest risk at a SBP of 130–140 mmHg.
Conclusion
Resting heart rate is a potent predictor of these renal outcomes, as well as their combination, in patients with cardiovascular disease. RHR at all SBP levels should be considered as a possible renal disease risk predictor and should be investigated as a treatment target with RHR‐reducing agents.
OBJECTIVEWe sought to perform a comprehensive assessment of long-term changes in left ventricular (LV) mass, focusing on new onset, persistence, regression and severity of LV hypertrophy (LVH), as ...well as independent demographic and clinical variables related to this dynamic process in a population-based sample.
DESIGN AND METHODA total of 1,113 participants with measurable echocardiographic parameters at baseline evaluation and at the end of a ten-year follow-up period were included in the present analysis. Cut-points for LVH were derived from current echocardiographic guidelines
RESULTSLVH prevalence significantly increased from 13% to 33%, as a consequence of new onset LVH in 254 and regression in 31 cases, respectively. Severe LVH increased about 1.8 times as compared to baseline and this trend was mainly related to the transition from mild and moderate to severe LVH in subjects with pre-existing cardiac hypertrophy. A number of baseline variables such as age, female gender, office and out-of-office systolic BP, body mass index, ATP 3 metabolic syndrome, and use of antihypertensive drugs were independently correlated either to new-onset and persistent LVH.
CONCLUSIONSLong-term LV mass changes in the general population are associated to a marked worsening in cardiovascular risk profile related to increased prevalence and severity of LVH. As BP, metabolic variables and BMI emerged as key correlates of a such dynamic process, our findings suggest that early interventions aimed to modify such risk factors at the community level may have a role in preventing new onset and progression LVH.
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