Cardiovascular Outcomes In Hypertensive Patients Research Articles

Abstract 11900: Potassium Magnesium Citrate is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone

Thiazide-type diuretics (TD) are the first-line treatment of hypertension in many guidelines because of its consistent benefit in lowering BP and cardiovascular risk. TD is also known to cause excess risk of diabetes mellitus (DM), which may limit its long-term use. Although hypokalemia was thought to be the main mechanism of TD-induced dysglycemia, potassium (K) supplementation alone does not consistently prevent TD-induced elevation in fasting plasma glucose (FPG). In addition to reducing serum K, TD triggers magnesium (Mg) depletion. However, it is unknown if Mg supplementation attenuates metabolic side effects of TD. Accordingly, we conducted a randomized double-blinded clinical trial in 60 hypertensive patients without DM to compare effects of KCl (40 meq daily) vs. KMgCitrate (Cit) powder containing identical amount of K, 20 meq of Mg, and 74 meq of Cit daily during chlorthalidone (CTD) treatment. Each patient received CTD alone (25 mg/day) for 3 weeks prior to randomization. The primary endpoint was the change in FPG after 4-month of treatment from baseline (CTD alone) after adjusting for baseline FPG as a covariate. The mean age of subjects was 59±11 years (45% Female, 30% Black participants). We found that CTD induced a significant rise in FPG, insulin, and a significant fall in serum K and 24-h urinary citrate excretion (all p < 0.05). We found that KMgCit significantly increased serum K, 24-hour urinary Mg, and 24-hour urinary Cit excretion; and attenuated the rise in FPG which was not observed with KCl (Figure 1 A-C). There were no significant differences in liver fat by MRI or fasting plasma insulin between the 2 groups. In conclusion, our study showed beneficial effects of magnesium supplementation in maintaining serum K and reversing effects CTD on plasma glucose, which may improve safety profile and optimize long-term cardiovascular outcomes in hypertensive patients.

Blood pressure control measures and cardiovascular outcomes: a prospective hypertensive cohort

Purpose We investigated whether blood pressure (BP) control measures, visit-to-visit BP variability, and time in therapeutic range (TTR) are associated with future cardiovascular outcomes in hypertensive patients. Materials and Methods Among 1,408 hypertensive patients without cardiovascular disease, we prospectively evaluated the incident major cardiovascular events over 6 years. In newly diagnosed patients, antihypertensive drug treatment was initiated. We estimated two markers of on-treatment BP control, (1) visit-to-visit BPV as the coefficient of variation of office systolic BP (BP-CV), and (2) TTR calculated as the percentage of office systolic BP measurements within 120–140mmHg across visits. Results The hypertensive cohort (672 males, mean age 60 years, 31% newly diagnosed) had a mean systolic/diastolic BP of 142/87 mmHg. The mean number of visits was 4.9 ± 2.6, while the mean attained systolic/diastolic BP during follow-up was 137/79 mmHg using 2.7 ± 1.1 antihypertensive drugs. The BP-CV and TTR were 9.1 ± 4.1% and 45 ± 29%, respectively, and the incidence of the composite outcome was 8.3% (n = 117). After adjustment for relevant confounders and standardization to z-scores, BP-CV and TTR were associated with a 43% (95% CI, 27–62%) increase and a 33% (95% CI, 15–47%) reduction in the outcome. However, the joint evaluation of TTR and BP-CV in a common multivariable model indicated that a standardized change of TTR was associated with the outcome to a greater extent than BP-CV (mean hazard ratios of 30% vs. 24%, respectively). When combined with the higher BP standardized-CV quartile, the lower TTR quartile predicted the outcome by 2.3 times (95% CI, 1.1–5.4) compared to the inverse TTR and BP-CV quartile pattern. Conclusion High BP-CV or low TTR was associated with future cardiovascular events in a cohort of treated hypertensive patients. As a determinant, the extent of TTR value appears greater than BP-CV when these measures are considered in the same multivariable model.

Abstract P312: High Potassium Intake Aggravates Cardiovascular Damage Accompanied By Premature Senescence In Hypertensive Apolipoproteine-ko Mice Under High Salt Diet

Increased sodium intake aggravates cardiovascular diseases. Salt substitute containing potassium chlorideimproves cardiovascular outcome in hypertensive patients with high cardiovascular risk, however it isunknown whether it is attributed to potassium (K+) supplementation or sodium reduction. Here, weinvestigate the role of high K+ intake on the development of hypertensive cardiac damage in the presenceor absence of high salt diet. 8-10 weeks old apolipoproteinE-deficient mice (apoE-KO) were fed a normalK+ (0,55%) or high K+ (5%) diet throughout the experiment. Two weeks after diet start,mice were infusedwith angiotensin (Ang)II (500ng/kg/min) for 28 days. Cardiac function was assessed by MRI. High K+ dietincreased serum K+ levels compared to mice fed a normal K+ diet (5.3±1.2 vs. 3.9±0.4mmol/L, p<0.05).Interestingly, high K+ diet did not affect blood pressure or cardiac function. As expected, aldosteroneexcretion was increased in high K+ diet group compared to normal K+ diet (132±20 vs 8±18 ng/24h,p<0.01). To evaluate the consequence of K+ mediated aldosterone secretion for hypertensivecardiovascular damage, we additionally treated our high K+ group with high salt diet (1%NaCl) in thedrinking water. High K+ induced aldosterone production in the presence of high NaCl intake aggravatedhypertensive cardiac damage characterized by higher left ventricular mass, more cardiac fibrosis andinflammation compared to mice fed a high K+ or a high NaCl diet solely. Furthermore, the simultaneousintake of high K+/NaCl diet, induced higher mitochondrial ROS production in cardiac endothelial cellscompared to high K+ or high NaCl diet alone. As a consequence, cellular senescence markers such as p16and p21 were significantly higher in mice fed a high K+ / NaCl diet. Of note, co-treatment withspironolactone (50mg/kg/day), significantly attenuated cellular senescence and cardiovascular damage inmice fed a high K+/NaCl diet. High K+ diet compared to normal K+ diet does not have a beneficial effecton hypertensive cardiac damage in apoE-KO mice. Moreover, the present study indicates that potassium-induced aldosterone production aggravates the detrimental effect of high salt intake on cardiac health inhypertension by influencing cardiac senescence.

IMPACT OF BLOOD PRESSURE VARIABILITY ON CARDIOVASCULAR MORTALITY IN CHRONIC KIDNEY DISEASE PATIENTS

Objective: It is well known that blood pressure (BP) variability is associated with development of target-organ damage and adverse cardiovascular outcome in hypertensive patients. However, the impact of BP variability (BPV) on cardiovascular outcome in chronic kidney disease patients (CKD) is unclear. Aim of the study was to examine the impact of home BPV on cardiovascular mortality in chronic kidney disease patients. Design and method: A total of 137 CKD patients, referred for evaluation at the Hypertension Unit of our department, underwent home BP monitoring. Participants were instructed to take duplicate morning and evening measurements in the sitting position, after 5-min sitting rest and with 1 min between measurements for 7 working days. The average home BP value of the morning, evening and all measurements was analyzed. Home BPV was quantified by using standard deviation (SD), coefficient of variation (CV) and morning minus evening BP values. Median follow-up for fatal cardiovascular events was 3 years. Statistical analysis was performed by means of cox regression analysis. Results: The study population consisted of 102 men (75%). Mean age was 70 years, mean office BP was 142/76 mmHg and mean home BP was 137/74 mmHg. During follow-up, there were 12 fatal cardiovascular events. The multivariate Cox regression analyses revealed that the SD of systolic home BP was an independent predictor of cardiovascular mortality (HR: 1.19, 95%CI 1.02–1.38, p = 0.022) after adjustment for age, sex, history of diabetes mellitus and hyperlipidemia, smoking, antihypertensive treatment and mean systolic home BP. Conclusions: Home BPV is an independent predictor of cardiovascular mortality in CKD patients

Does Blood Pressure Variability Affect Hypertension Development in Prehypertensive Patients?

Blood pressure variability (BPV) is associated with end organ damage and cardiovascular outcomes in hypertensive patients. Prehypertensive patients frequently develop hypertension (HT). The purpose of the present study was to evaluate the effect of BPV on the development of HT. Two hundred and seven prehypertensive patients from the Cappadocia cohort were monitored over 2 years, and 24-hour ambulatory blood pressure monitoring (ABPM), office BP, and home BP measurements were subsequently performed at 4- to 6-month intervals. BPV was calculated as average real variability (ARV) from 24-h ABPM data, home BP, and office BP measurements at first visit. The relationship was evaluated between baseline ARV and the development of HT. HT was diagnosed in 25.60% of subjects. Baseline 24-hour ABPM systolic blood pressure (SBP)ARV and diastolic blood pressure (DBP)ARV and home SBPARV were significantly higher in patients who developed HT than the other patients (P 0.006, 0.001 and 0.006, respectively). Baseline 24-hour ABPM SBPARV and home SBPARV exceeding the 90th percentile were identified as parameters affecting development of HT at logistic regression analysis. In conclusion, our prospective observational cohort study showed that short-term BPV in particular can predict the development of HT in the prehypertensive population.

Impact of Fasting on Cardiovascular Outcomes in Patients With Hypertension.

Fasting has been frequently practiced for religious or medical purposes worldwide. However, limited literature assesses the impact of different fasting patterns on the physiologic and cardiac-related parameters in patients with hypertension. This review aims to examine the effect of fasting on cardiovascular outcomes in hypertensive patients. Medline, Embase, and Cochrane library were systematically screened until March 2021 for observational prospective cohorts investigating the effect of fasting on cardiovascular outcomes. Articles were assessed by searching for hypertension and fasting, both as Medical Subject Headings (MeSH) terms and text words. The review included studies assessing Ramadan, intermittent, and water-only fasting. Water-only fasting reduces body weight, blood pressure, and lipolytic activity of fasting hypertensive patients without affecting average heart rate. Ramadan fasting enhances lipid profile, although it shows conflicting results for body weight, blood pressure, and heart rate variability. Considering the limited studies in this field, further research should be conducted to support the clinical impact of fasting on the cardiovascular health of patients with hypertension.

New-Onset Diabetes, Endothelial Dysfunction, and Cardiovascular Outcomes in Hypertensive Patients: An Illness-Event Model Analysis.

Background. Insulin resistance and endothelial dysfunction are common findings in hypertensives, both predisposing to a higher risk of diabetes and cardiovascular events. We designed this study to evaluate the role of endothelial dysfunction in three pathogenetic pathways: (1) from baseline to cardiovascular events, (2) from baseline to diabetes, and (3) from new-onset diabetes to cardiovascular events. Methods. We enrolled 653 Caucasian never-treated hypertensives. Endothelial dysfunction was investigated by strain-gauge plethysmography; incident diabetes and cardiovascular events were evaluated by an illness-event model analysis. Results. During the follow-up (median 113 months), we documented 191 new cardiovascular events and 92 new cases of diabetes. In a multiple Cox regression analysis, acetylcholine-stimulated forearm blood flow [100% decrease, hazard ratio: 2.42 (95% confidence interval = 1.72–3.40)] and serum high-sensitivity C-reactive protein [hazard ratio: 1.30 (95% confidence interval = 1.21–1.40)] had an independent association with cardiovascular outcomes. The incidence rate of cardiovascular outcomes in diabetes-developer patients was higher than in the diabetes-free ones (34.9 vs. 2.5 events per 100 persons-year). In an illness-event model, a 100% decrease in forearm blood flow was associated with a 55.5% hazard ratio increase (hazard ratio: 1.56, 95% confidence interval: 1.33–1.82) of transition 1 (from baseline status to cardiovascular events) and to an almost doubled increase (hazard ratio: 2.54, 95% CI: 2.00–3.25) of the risk of transition 2 (from baseline status to diabetes). No such effects were found in transition 3 (from diabetes to cardiovascular events). Conclusions. Endothelial dysfunction plays a primary role in the pathways leading to diabetes and cardiovascular events in hypertensives. When diabetes is overt, endothelial dysfunction has no predictive value for subsequent cardiovascular events.

Association of metabolic syndrome with cardiovascular outcomes in hypertensive patients: a systematic review and meta-analysis.

The association between metabolic syndrome (MetS) and cardiovascular outcomes in patients with hypertension is still controversial. This meta-analysis sought to evaluate the association of MetS with cardiovascular outcomes in hypertensive patients. Two authors comprehensively searched PubMed and Embase databases from their inception to April 18, 2020 for the longitudinal studies that evaluated the association of MetS with cardiovascular outcomes in patients with hypertension. The main outcomes were major adverse cardiovascular events (myocardial infarction, revascularization, stroke, hospitalization due to heart failure, etc.) and stroke. Eight studies consisting of 36,614 hypertensive patients were identified and analyzed. Meta-analysis indicated that MetS was associated with an increased risk of major adverse cardiovascular events (risk ratio [RR] 1.55; 95% confidence intervals [CI] 1.28-1.87), cardiovascular mortality (RR 1.44; 95%CI 1.13-1.82), and stroke (RR 1.46; 95%CI 1.22-1.75), respectively. Sensitivity analysis further confirmed the robustness of the prognostic value of MetS. MetS is associated with higher risk of major adverse cardiovascular events, cardiovascular mortality, and stroke in patients with hypertension. Determination of MetS may contribute to improving cardiovascular risk stratification in hypertension.

Association of serum uric acid with mortality and cardiovascular outcomes in patients with hypertension: a meta-analysis.

Studies on the association of uric acid with mortality and cardiovascular outcomes in patients with hypertension have produced contradictory results. The objective of this meta-analysis was to evaluate the prognostic utility of uric acid in hypertensive patients. We comprehensively searched PubMed and Embase databases (until July 31, 2020) to identify eligible studies that reported the association of uric acid with mortality and cardiovascular outcomes in hypertensive patients. Outcome measures included cardiovascular or all-cause mortality, coronary artery disease (CAD), stroke, and major adverse cardiovascular events (MACEs). Eleven eligible studies of 49,800 hypertensive patients were identified. For patients with the highest than those with reference lower group of uric acid level, the pooled hazard ratio (HR) was 1.51 (95% confidence interval [CI] 1.12-2.02) for all-cause mortality, 1.68 (95% CI 1.28-2.20) for cardiovascular mortality, 1.31 (95% CI 1.10-1.55) for CAD, and 1.48 (95% CI 1.28-1.70) for MACEs. However, there was no significant association between elevated uric acid level and incident stroke in hypertensive patients. This meta-analysis indicates that elevated uric acid level is significantly associated with an increased risk of cardiovascular or all-cause mortality, CAD and MACEs in hypertensive patients. Hypertensive patients with highest uric acid level exhibited a tendency for reduced risk of stroke, but the difference is not significant.

Association of clinic and ambulatory heart rate parameters with mortality in hypertension.

Resting heart rate (HR) taken in the office has been shown to be associated with cardiovascular outcomes in the general population, hypertension and heart failure. It is unknown whether 24-h oscillographic pulse rate measurement as an approximation of HR derived from ambulatory blood pressure monitoring (ABPM) associates with cardiovascular outcomes in hypertensive patients. We evaluated ABPM recordings from 56 901 patients with complete 3373 421 HR measures entering the final analysis from the Spanish Blood Pressure Monitoring Registry for a median follow-up time of 5.1 years. We explored the association of office HR, mean 24-h HR, mean day HR, mean night HR as well as day-night HR differences, morning mean HR, morning HR surge and night peak HR to all-cause death, cardiovascular death and noncardiovascular death. Data were analyzed by Cox regression analysis, analysis of variance and chi-square test. The Spanish ABPM Registry recorded data in 223 primary care centers in Spain from 2004 until 31 December 2014 at the end of recruitment. Office HR was 3.5 bpm higher than mean 24-h HR, office mean HR versus mean night was 10.4 bpm higher and mean day versus mean night HR 9.3 bpm higher, while there were no relevant difference between office and mean day HR. Office mean, 24-h day and night HR more than 90 bpm were associated with an increased risk for all-cause and noncardiovascular death, whereas for cardiovascular death only mean night HR was predictive. The strongest association to all-cause death was observed with mean night HR [hazard ratio 3.80 (2.87-5.03)], mean 24-h HR [2.85 (2.30-3.54)] and mean day HR [2.22 (1.83-2.70)]. Day-night dipping of more than 8 bpm was associated with a 20% lesser risk on all-cause, cardiovascular and noncardiovascular death. Results were robust after adjusting for relevant risk indicators. HR parameters derived from ABPM provide important information, in particular association with death by mean night HR, mean 24-h HR and reduced day-night HR dipping less than 8 bpm superior to office HR.

Short-Term Prognosis Value of sST2 for an Unfavorable Outcome in Hypertensive Patients.

Background sST2 represents a useful biomarker for the diagnosis and prognosis of patients with heart failure, but limited data is available on its role in patients with hypertension. The aim of this study is to evaluate the short-term prognosis value of sST2 for an unfavorable outcome in hypertensive patients. Methods This was a prospective observational study which enrolled 80 patients with hypertension, who were followed for one year. All patients underwent clinical, laboratory (including sST2), and echocardiographic assessment at baseline. The patients were grouped according to the cardiovascular (CV) events reported during the follow-up: group A (with CV events) and group B (without CV events). Results Overall, 59 CV events were reported during the follow-up period. Compared to group B, the patients in group A had significantly higher sST2 levels, a higher number of CV risk factors, and a higher left ventricle mass. Except for the diastolic dysfunction parameters, the echocardiographic findings were similar in the two groups. Patients in group A had a lower E/A ratio, larger deceleration time, and increased telediastolic pressure as quantified by the E/E/p = 0.006, Kaplan-Meier analysis). Conclusions sST2 levels were correlated with the risk of adverse CV outcomes in hypertensive patients and may represent a useful prognostic marker in these patients.

Roles of arterial pressure volume index and arterial velocity pulse index trajectories in risk prediction in hypertensive patients with heart failure with preserved ejection fraction

ABSTRACTBackground: Arterial pressure volume index (API) and arterial velocity pulse index (AVI) contribute to the development of vascular damage and cardiovascular disease. However, the relationship between common API/AVI trajectories and cardiovascular outcomes in hypertensive patients with heart failure with preserved ejection fraction (HFpEF) is unknown.Methods: A total of 488 consecutive hypertensive patients with HFpEF who repeatedly underwent API/AVI measurements were prospectively examined. We then applied API/AVI measurements into actual clinical practice. Latent mixture modeling was performed to identify API/AVI trajectories. Hazards ratios (HRs) were measured using Cox proportional hazard models.Results: We identified four distinct API/AVI trajectory patterns: low (7.6%), moderate (43.8%), high (28.9%), and very high (19.7%). Compared with the low group, higher API trajectories were associated with increased risk of total cardiovascular events (high group, adjusted HR: 2.91, 95% confidence interval [CI]: 1.97–4.26; very high group, adjusted HR: 2.46, 95%CI: 1.18–3.79). Consistently, higher AVI trajectories were also associated with a higher risk of total cardiovascular events (high group, adjusted HR: 2.58, 95%CI: 1.23–5.47; very high group, adjusted HR: 3.12, 95%CI: 1.83–6.08), compared with the low trajectory group.Conclusion: High API/AVI trajectories are strong predictors of cardiovascular risk in hypertensive patients with HFpEF. Among these patients, measuring API/AVI may improve risk stratification and provide additional information to tailor treatment strategies.

Effects of blood pressure goals on cardiovascular outcomes in hypertensive patients.

IntroductionThe aim of the study was to evaluate the effects of blood pressure (BP) goals on cardiovascular outcomes in hypertensive patients.Material and methodsPrimary hypertensive patients were retrospectively enrolled from outpatient clinics. The demographics, comorbidities, laboratory parameters and glomerular filtration rate (GFR) were collected. All participants were followed for 1 year. Cardiovascular outcomes included composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal ischemic stroke/transient ischemic attack. Adverse event was defined as falling down and GFR decrease at follow-up.ResultsA total of 1226 patients were included. Based on therapeutic BP goals, participants were divided into low (< 130/80 mm Hg) and high (< 140/90 mm Hg) therapeutic goal groups and an uncontrolled hypertension (≥ 140/90 mm Hg) group. Compared to the low therapeutic goal group, patients in the uncontrolled group were older and more likely to be smokers, have longer duration of hypertension, diabetes mellitus, lower GFR and higher prevalent ischemic stroke (p < 0.05). Patients in the uncontrolled hypertension group had higher incidence of composite endpoints than low and high therapeutic goal groups. Two cases of falling down were observed in the low therapeutic goal group and no significant changes in GFR were observed. With adjustment for confounding factors, the uncontrolled hypertension group had higher risk of composite endpoints compared to low and high therapeutic goal groups, and these benefits were more prominent in the low versus high therapeutic goal group.ConclusionsIn hypertension patients, when compared to uncontrolled hypertension patients, low therapeutic BP goal is associated with better cardiovascular outcomes than high therapeutic BP goal.

The benefits of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers combined with calcium channel blockers on metabolic, renal, and cardiovascular outcomes in hypertensive patients: a meta-analysis.

The prevalence of hypertension and its associated complications are markedly growing. Most patients need more than one drug to achieve blood pressure (BP) target. However, most guidelines only focus on the first-line treatment. We conducted a meta-analysis to explore the benefits of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) combined with calcium channel blockers (CCBs) on metabolic, renal, and cardiovascular outcomes in hypertensive patients. A systematic literature search was conducted in MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov (until April 7, 2016) to identify randomized controlled trials (RCTs) comparing the benefits of ACEIs/ARBs combined with CCBs versus other dual or triple combinations on clinical outcomes in hypertensive patients. Random effects models were used to compute the weighted mean difference (WMD) for continuous variables. Sixty RCTs (48,913 patients) were identified. When compared with other combinations, the combination of ACEIs/ARBs and CCBs had comparable WMD of systolic as well as diastolic BP (73 study arms) but provided better benefits on metabolic parameters, such as HDL, FBS, HbA1C, and serum uric acid; renal functions, including serum creatinine and estimated glomerular filtration rate; and cardiovascular diseases, including reduction of all cardiovascular events, myocardial infarction, and syncope/hypotension. A significant increase of serum potassium was observed. The combination of ACEIs/ARBs with CCBs has superior benefits on metabolic, renal, and cardiovascular outcomes in hypertensive patients. Therefore, this combination should be considered whenever monotherapy does not achieve the guideline target.

IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)

BackgroundCertain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.ObjectivesWe tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics.MethodsNORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386 days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively.FindingsFrom 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p = 0.012; p = 0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p = 0.027) and percentage of plaque occupied by necrotic core (p = 0.011), as well as lipid core burden index (p = 0.024) in the worst 4 mm segment.InterpretationOur study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.

Comparison of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular outcomes in hypertensive patients with type 2 diabetes mellitus: A PRISMA-compliant systematic review and meta-analysis.

Background:Previous studies seem to show different effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on cardiovascular (CV) events in hypertensive patients with type 2 diabetes mellitus (T2DM). Our objective was to analyze which are preferable on the incidence of all-cause mortality, CV death, and major CV events in hypertensive patients with T2DM.Methods:PubMed, MEDLINE, and EMBASE were searched for randomized controlled trials (RCTs) published up to June 2016 with ACEI or ARBs as the intervention for hypertensive patients with T2DM. The primary end points were all-cause mortality and CV death. The secondary end points were myocardial infarction (MI), stroke, heart failure (HF), and CV events. Two investigators extracted the information independently. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present.Results:A total of 13 trials were included for analysis, 5 ACEI trials (24,976 patients) and 8 ARB trials (22,032 patients) followed for a mean of 3.8 years. Treatment with ACEI was associated with significantly reduction in all-cause mortality [odds ratio (OR) 0.87; 95% confidence interval (95% CI), 0.80–0.94], CV death (OR 0.81; 95% CI, 0.68–0.98), and other CV outcomes such as MI (0R 0.77; 95% CI, 0.66–0.90), stroke (OR 0.88; 95% CI, 0.78–0.99), HF (OR 0.65; 95% CI, 0.47–0.90), and CV events (OR 0.83; 95% CI, 0.73–0.95), whereas ARBs therapy had no significant reduction in the results of many primary and secondary outcomes.Conclusion:This meta-analysis suggests that treatment with ACEI showed a significant CV protection for all-cause mortality, CV death, and major CV events, whereas ARBs had no benefits on these outcomes except MI. In consideration of high mortality and morbidity, ACEI was preferable than ARBs on patients with hypertension and T2DM.

Association of Abnormal Serum Potassium Levels with Arrhythmias and Cardiovascular Mortality: a Systematic Review and Meta-Analysis of Observational Studies.

To provide the first systematic review and meta-analysis of observational studies on the association of abnormal serum potassium and cardiovascular outcomes. Medline and ISI Web of Knowledge were systematically searched from inception until November 24, 2017. Data synthesis of relevant studies was performed using random effects model meta-analyses. Meta-analyses included 310,825 participants from 24 studies. In the older general population, low serum potassium was associated with a 1.6-fold increased risk of supraventricular arrhythmias (risk ratio [95% confidence interval] 1.62 [1.02-2.55]). Contrarily, high serum potassium was associated with increased cardiovascular mortality (CVM) (1.38 [1.14-1.66]). In patients with acute myocardial infarction, the risk of ventricular arrhythmias was increased for high serum potassium (2.33 [1.60-3.38]). A U-shaped association was observed with a composite cardiovascular outcome in hypertensive patients (2.6-fold increased risk with hypokalemia and 1.7-fold increased risk with hyperkalemia), with CVM in dialysis patients (1.1-fold increased risk with hypokalemia and 1.4-fold increased risk with hyperkalemia) and with CVM in heart failure patients (albeit not statistically significant). Further, only hyperkalemia was associated with an increased risk of a composite cardiovascular outcome in both dialysis (1.12 [1.03-1.23]) and chronic kidney disease (1.34 [1.06-1.71]) patients. Controlled clinical trials are needed to determine which populations may profit from more frequent potassium-monitoring and subsequent interventions, e.g., change or withdrawal of potassium-influencing drugs, in order to restore normal values and prevent cardiovascular outcomes. Registration in PROSPERO (Centre for Reviews and Dissemination University of York, York, UK): CRD42016048897 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=48897 ).

The overdriven glomerulus as a cardiovascular risk factor

In a large cohort of patients referred for the diagnosis of hypertension by ambulatory blood pressure monitoring, the risk for cardiovascular events associated with glomerular hyperfiltration (hazard ratio: 1.53) was higher than that associated with diabetes (hazard ratio: 1.43) or with a 10 mmHg higher 24-hour systolic blood pressure (hazard ratio: 1.37) and was identical to that by smoking (hazard ratio: 1.53). Reducing glomerular hyperfiltration may improve cardiovascular outcomes in hypertensive patients, an issue that remains to be tested in appropriate randomized clinical trials.

MPS 04-03 MORNING HYPERTENSION WITH NOCTURNAL HYPERTENSION WAS RELATED WITH HIGHER CENTRAL BLOOD PRESSURE AND INCREASED ARTERIAL STIFFNESS

Objective: Recent study reported that morning hypertension was associated with worse cardiovascular outcomes in hypertensive patients. There are not enough studies about the inter-relationship between morning hypertension/nocturnal hypertension and central hemodynamics until now. Design and Method: Ambulatory blood pressure monitoring and central BP were measured in 1062 consecutive subjects enrolled in Cardiovascular and Metabolic Disease Etiology Research Center - HIgh Risk Cohort (CMERC-HI, NCT02003781). Morning hypertension was defined as mean systolic BP (SBP) within 2 hours after awake > 135mmHg and nocturnal hypertension as mean night SBP > 120mmHg or diastolic BP (DBP ≥ 70mmHg. We divided morning hypertension into 3 subtypes. 1) morning normotension 2) morning hypertension without nocturnal hypertension and 3) morning hypertension with nocturnal hypertension. Results: Morning hypertension was found in 494 (46.5%) patients and morning hypertension with nocturnal hypertension was in 403 (37.9%) patients. Central SBP/DBP (129/79 ± 21/11 vs. 116/75 ± 17/9mmHg, both p < 0.001), augmentation index (AIx, 30.6 ± 11.4 vs. 27.4 ± 13.3, p < 0.001) and carotid to femoral pulse wave velocity (cfPWV, 986 ± 245 vs. 887 ± 198 cm/s, p < 0.001) were higher in morning hypertension than in morning normotension. There were significant difference in central SBP (120/75 ± 16/8 vs. 116/75 ± 17/9mmHg, p = 0.027 for SBP, p = 0.746 for DBP) and cfPWV (932 ± 220 vs. 887 ± 198 cm/s, p = 0.049) not 24-hour SBP/DBP (p = 0.150/p = 0.219) between morning normotension and morning hypertension without nocturnal hypertension group. The morning hypertensive patients with nocturnal hypertension had higher central SBP/DBP (131/79 ± 21/11 vs. 120/75 ± 16/8mmHg, both p < 0.001) and cfPWV (998 ± 248 vs. 932 ± 220 cm/s, p = 0.020) compared to those without nocturnal hypertension. Conclusions: We reported that morning hypertension, especially with nocturnal hypertension was related to higher central BP and increased arterial stiffness. Further studies for assessing whether morning hypertension with or without nocturnal hypertension relates to clinical outcomes should be warranted.

Effects of blood pressure lowering treatment in hypertension: 8. Outcome reductions vs. discontinuations because of adverse drug events - meta-analyses of randomized trials.

Previous meta-analyses of randomized controlled trials (RCTs) of blood pressure (BP)-lowering treatment provided overwhelming evidence that treatment markedly reduces risk of cardiovascular outcomes in hypertensive patients. However, adverse events associated with BP-lowering treatment have never been surveyed systematically. Identifying among BP-lowering RCTs those reporting a common and meaningful index of treatment-attributed adverse events, and describing the burden of these adverse events accompanying the benefits of mortality and morbidity reduction induced by treatment. The database consisted of the BP-lowering RCTs (active vs. placebo or less active treatment) we have described (70 RCTs, 255 970 participants, 1 091 964 patient-years). A common index of relevant adverse events was identified as permanent treatment discontinuation attributed to treatment adverse events. Risk ratios and 95% confidence intervals, standardized to a SBP/DBP reduction of 10/5 mmHg, of seven fatal and nonfatal outcomes and of treatment discontinuations for adverse events were calculated (random-effects model). The relationships of outcome reductions and discontinuation excess to SBP and DBP reductions were investigated by meta-regressions. Forty-four RCTs provided data on treatment discontinuations for adverse events and six more on serious adverse events because of treatment (179 949 patients, 719 796 patient-years). In these 50 RCTs, a significant 24% reduction of major cardiovascular event risk was associated with a significant 89% increase in the risk of discontinuations (33 major cardiovascular effects prevented and 84 excess discontinuations/1000 patients for 5 years). Metaregression analysis indicated that both outcome reductions and treatment discontinuation excess were significantly related to the extent of SBP and DBP reduction, but absolute treatment discontinuation excess disproportionally increased with larger BP reductions than increase in outcome risk reduction. Furthermore, a standard SBP reduction was found associated with a constant relative reduction, but a smaller absolute reduction of cardiovascular events, and a greater relative excess of treatment discontinuations when the achieved SBP was below 130 mmHg rather than in higher ranges. The burden of adverse events associated with BP-lowering treatment should be considered not to deny patients the overwhelming benefits of BP lowering, but whenever the extent of the BP lowering or the BP target to be achieved are discussed.