Total Cardiovascular Mortality Research Articles

Blood pressure targets for hypertension in people with chronic renal disease.

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease, development of end-stage renal disease, and all-cause mortality. It affects around 10% of the population worldwide. The prevalence of hypertension in people with CKD ranges from 22% in stage 1 to 80% in stage 4. Elevated arterial blood pressure is one of the major independent risk factors for adverse cardiovascular events. Thereby, reducing blood pressure to below standard targets may be beneficial but could also increase the risk of adverse events. The optimal blood pressure target in people with hypertension and CKD remains unknown. Primary: to compare the effects of standard and lower-than-standard blood pressure targets for hypertension in people with chronic kidney disease on mortality and morbidity outcomes. Secondary: to assess the magnitude of reductions in systolic and diastolic blood pressure, the proportion of participants reaching blood pressure targets, and the number of drugs necessary to achieve the assigned target. We used standard, extensive Cochrane search methods. We searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, one other database, and two trial registers up to 8 February 2023. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions. We included randomized controlled trials (RCTs) in people with hypertension and CKD that provided at least twelve months' follow-up. Eligible interventions compared lower targets for systolic/diastolic blood pressure (130/80 mmHg or lower) to standard targets for blood pressure (140 to 160/90 to 100 mmHg or lower). Participants were adults with CKD and elevated blood pressure documented in a standard way on at least two occasions, or already receiving treatment for elevated blood pressure. We used standard Cochrane methods. Our critical outcomes were: total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease. Important outcomes were: participant withdrawals due to adverse effects, and number of participants with a doubling of serum creatinine level or at least a 50% reduction in the glomerular filtration rate (GFR) at the end of the study. We used GRADE to assess the certainty of the evidence for the critical outcomes. This review received no funding. We included six RCTs that contributed data for meta-analysis, involving 7348 participants overall (range 840 to 4733 people per study). The mean follow-up was 3.6 years (range 1.0 to 8.0 years). Three studies were publicly funded, two were privately funded, and one had both public and private funding. All RCTs provided individual participant data. None of the included studies blinded participants or clinicians because of the need to titrate antihypertensive drugs to reach a specific blood pressure target. However, an independent committee blinded to group allocation assessed clinical events in all studies. Critical outcomes. Compared with standard blood pressure targets, lower targets likely result in little to no difference in total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.76 to 1.06; 6 studies, 7348 participants), total serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 7348 participants), and total cardiovascular events (RR 1.00, 95% CI 0.87 to 1.15; 5 studies, 6508 participants), all with moderate-certainty evidence. Compared with standard blood pressure targets, lower targets may result in little to no difference in cardiovascular mortality (RR 0.90, 95% CI 0.70 to 1.16; 6 studies, 7348 participants) and progression to end-stage renal disease (RR 0.94, 95% CI 0.80 to 1.11; 4 studies, 4788 participants), both with low-certainty evidence. Important outcomes. We found little to no differences in: participant withdrawals due to adverse effects; and the number of participants with a doubling of serum creatinine level, or at least a 50% reduction in GFR at the end of the study. Exploratory outcomes. Compared to the standard blood pressure target groups, participants in the lower target groups achieved lower systolic and diastolic blood pressure values after one year, and required a higher number of antihypertensive drugs at the end of the studies. A higher proportion of participants in the standard blood pressure target groups achieved the targets they were assigned than did participants in the intensive target groups. Compared to a standard blood pressure target, lower blood pressure targets probably result in little to no difference in total mortality, total serious adverse events, and total cardiovascular events, and may result in little to no difference in total cardiovascular mortality or in the progression to end-stage renal disease in people with hypertension and CKD. However, the evidence underpinning these conclusions has several limitations. All studies were open design, blood pressure measurement was performed at a medical office, and there was scant information about adverse events. Future research should include high-quality adverse event data, report results for people with different levels of proteinuria, and consider out-of-office blood pressure monitoring. Several studies are ongoing, and may provide new evidence for this topic in the near future.

Association of HDL cholesterol with all-cause and cardiovascular mortality in primary hypercholesterolemia

Background and aimsRecent reports have shown that subjects with high high-density lipoprotein cholesterol (HDLc) levels are paradoxically at increased risk for all-cause and cardiovascular mortality. The aim was to study the association of HDLc concentration with mortality in subjects with high cholesterol. MethodsWe analyzed total mortality, cardiovascular mortality, and non-cardiovascular mortality in a cohort of 2992 subjects with primary hypercholesterolemia, who were followed for 10.2 years (range 1–25 years), with a total of 30,602 subject-years of follow-up. ResultsDuring follow-up, 168 subjects died, with 52 (13.7 %), 105 (4.80 %), and 11 (2.60 %) in the low, normal, and high HDLc groups, respectively (p < 0.001). The risk of death was 2.89 times higher (95 % confidence interval (CI), 1.50–5.57, p < 0.001) in subjects in the low HDLc group compared to those in the high HDLc group and 1.48 times higher (95 % CI 0.80–2.76, p = 0.214) in the normal HDLc group compared to the high HDLc group. However, HDLc concentration and HDLc groups based on HDLc concentration were not independently associated with mortality in Cox regression analysis. Cardiovascular and non-cardiovascular mortalities showed similar results. ConclusionsAll types of mortality were lower in subjects with primary hypercholesterolemia and with high HDLc in univariate analysis. Elevated HDLc was not associated with total, cardiovascular, and non-cardiovascular mortality when adjusted for major cardiovascular risk factors.

Heat and cause-specific cardiopulmonary mortality in Germany: a case-crossover study using small-area assessment

High temperatures have been associated with increased mortality, with evidence reported predominately in large cities and for total cardiovascular or respiratory deaths. This case-crossover study examined heat-related cause-specific cardiopulmonary mortality and vulnerability factors using small-area data from Germany. We analyzed daily counts of cause-specific cardiopulmonary deaths from 380 German districts (2000-2016) and daily mean temperatures estimated by spatial-temporal models. We applied conditional quasi-Poisson regression using distributed lag nonlinear models to examine heat effects during May-September in each district and random-effects meta-analysis to pool the district-specific estimates. Potential individual- and district-level vulnerability factors were examined by subgroup analyses and meta-regressions, respectively. Heat was associated with increased mortality risks for all cardiopulmonary sub-causes. The relative risk (RR) of total cardiovascular and respiratory mortality for a temperature increment from the 75th to the 99th percentile was 1.24 (95% confidence interval: 1.23, 1.26) and 1.34 (1.30, 1.38), respectively. The RRs of cardiovascular sub-causes ranged from 1.16 (1.13, 1.19) for myocardial infarction to 1.32 (1.29, 1.36) for heart failure. For respiratory sub-causes, the RR was 1.27 (1.22, 1.31) for COPD and 1.49 (1.42, 1.57) for pneumonia. We observed greater susceptibility related to several individual- and district-level characteristics, e.g., among females or in highly urbanized districts. Heat vulnerability factors remained consistent between urban and rural areas. Our study highlights heat-related increases in cause-specific cardiopulmonary mortality across Germany and identifies key vulnerability factors, offering insights for improving public health practices to mitigate heat-related health impacts. European Union's Horizon 2020 research and innovation program; Helmholtz Associations Initiative and Networking Fund.

Artificial Intelligence Applied to Electrical and Non-Invasive Hemodynamic Markers in Elderly Decompensated Chronic Heart Failure Patients.

The first aim of this study was to assess the predictive power of Tend interval (Te) and non-invasive hemodynamic markers, based on bioimpedance in decompensated chronic heart failure (CHF). The second one was to verify the possible differences in repolarization and hemodynamic data between CHF patients grouped by level of left ventricular ejection fraction (LVEF). Finally, we wanted to check if repolarization and hemodynamic data changed with clinical improvement or worsening in CHF patients. Two hundred and forty-three decompensated CHF patients were studied by 5 min ECG recordings to determine the mean and standard deviation (TeSD) of Te (first study). In a subgroup of 129 patients (second study), non-invasive hemodynamic and repolarization data were recorded for further evaluation. Total in-hospital and cardiovascular mortality rates were respectively 19 and 9%. Te was higher in the deceased than in surviving subjects (Te: 120 ± 28 vs. 100 ± 25 ms) and multivariable logistic regression analysis reported that Te was related to an increase of total (χ2: 35.45, odds ratio: 1.03, 95% confidence limit: 1.02-1.05, p < 0.001) and cardiovascular mortality (χ2: 32.58, odds ratio: 1.04, 95% confidence limit: 1.02-1.06, p < 0.001). Subjects with heart failure with reduced ejection fraction (HFrEF) reported higher levels of repolarization and lower non-invasive systolic hemodynamic data in comparison to those with preserved ejection fraction (HFpEF). In the subgroup, patients with the NT-proBNP reduction after therapy showed a lower rate of Te, heart rate, blood pressures, contractility index, and left ventricular ejection time in comparison with the patients without NT-proBNP reduction. Electrical signals from ECG and bioimpedance were capable of monitoring the patients with advanced decompensated CHF. These simple, inexpensive, non-invasive, easily repeatable, and transmissible markers could represent a tool to remotely monitor and to intercept the possible worsening of these patients early by machine learning and artificial intelligence tools.

Wildfire-related PM2.5 and cardiovascular mortality: A difference-in-differences analysis in Brazil

Brazil has experienced unprecedented wildfires recently. We aimed to investigate the association of wildfire-related fine particulate matter (PM2.5) with cause-specific cardiovascular mortality, and to estimate the attributable mortality burden. Exposure to wildfire-related PM2.5 was defined as exposure to annual mean wildfire-related PM2.5 concentrations in the 1-year prior to death. The variant difference-in-differences method was employed to explore the wildfire-related PM2.5-cardiovascular mortality association. We found that, in Brazil, compared with the population in the first quartile (Q1: ≤1.82 μg/m3) of wildfire-related PM2.5 exposure, those in the fourth quartile (Q4: 4.22–17.12 μg/m3) of wildfire-related PM2.5 exposure had a 2.2% (RR: 1.022, 95% CI: 1.013–1.032) higher risk for total cardiovascular mortality, 3.1% (RR: 1.031, 95% CI: 1.014–1.048) for ischaemic heart disease mortality, and 2.0% (RR: 1.020, 95% CI: 1.002–1.038) for stroke mortality. From 2010 to 2018, an estimation of 35,847 (95% CI: 22,424–49,177) cardiovascular deaths, representing 17.77 (95% CI: 11.12–24.38) per 100,000 population, were attributable to wildfire-related PM2.5 exposure. Targeted health promotion strategies should be developed for local governments to protect the public from the risk of wildfire-related cardiovascular premature deaths.

Benefits of intravenous iron supplementation in heart failure.

Introduction: Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF) and is estimated to be present in up to 80% of acute patients regardless of their ejection fraction. Randomized controlled trials have shown that supplementary intravenous iron results in improved clinical outcomes; however, the current understanding of the effects of intravenous iron on morbidity and mortality remains limited. Study and results: The meta-analysis pooled individual participant data from three randomized placebo-controlled trials of ferric carboxymaltose (FCM) in adult patients (n = 4,501) with heart failure and iron deficiency (CONFIRM-HF, AFFIRM-AHF, and HEART-FID). FCM therapy significantly reduced the co-primary composite endpoint of total cardiovascular hospitalizations and cardiovascular death, with a rate ratio (RR 0.86; 95% CI 0.75 to 0.98; p = 0.029). FCM therapy was associated with a 17% relative rate reduction in total cardiovascular hospitalizations (RR 0.83; 95% CI 0.73 to 0.96; p = 0.009) and a 16% relative rate reduction in total heart failure hospitalizations (RR 0.84; 95% CI 0.71 to 0.98; p = 0.025). Lessons learned: The meta-analysis shows that in iron-deficient patients with heart failure and reduced or mildly reduced left ventricular ejection fraction, intravenous ferric carboxymaltose (FCM) is associated with a reduced risk of total cardiovascular hospitalization and cardiovascular mortality. These findings indicate that intravenous FCM should be considered in iron-deficient patients with heart failure and reduced or mildly reduced ejection fractions.

Comparison of ticagrelor and clopidogrel in anemic patients with acute coronary syndrome: efficacy and safety outcomes over one year.

This retrospective study aimed to investigate the potential impact of ticagrelor and clopidogrel treatment on cardiovascular outcomes in patients with anemia and acute coronary syndrome (ACS) and to provide insights into the optimal therapeutic approach for this vulnerable patient population. A retrospective research design was employed, involving patients diagnosed with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) between 2014 and 2021. Inclusion criteria required a hemoglobin level below 12mg/dL and a minimum 12-month P2Y12 inhibitor treatment. Comprehensive clinical, biochemical, and echocardiographic data were collected from the hospital's electronic repository. The primary efficacy endpoint was major adverse cardiovascular events (MACE), encompassing total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke. Major hemorrhage was the primary safety endpoint. Secondary outcomes included total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke, individually. Patients treated with ticagrelor (n = 118) and clopidogrel (n = 538) were compared. No significant difference was observed in major adverse cardiovascular events (MACE) and major bleeding between ticagrelor and clopidogrel treatment groups (MACE: clopidogrel 10.0% vs. ticagrelor 11.0%, p = 0.75; major bleeding: clopidogrel 2.8%, ticagrelor 2.5%, p = 0.88). Patients with hemoglobin levels ≤ 8mg/dL demonstrated significantly higher MACE and major bleeding rates in the ticagrelor group (p = 0.008 and p = 0.002, respectively). Among patients aged ≥ 75 years, ticagrelor treatment was associated with a higher risk of major bleeding (p = 0.04). Ticagrelor and clopidogrel exhibited comparable efficacy and safety outcomes in anemic ACS patients over a one-year period. Although ticagrelor demonstrated superiority in reducing ischemic events, it is crucial to recognize the limitations of retrospective studies in informing clinical practice. This study offers valuable insights into tailoring antiplatelet therapy for anemic ACS patients and provides guidance for personalized treatment strategies, acknowledging the hypothesis-generating nature of retrospective analyses.

Toxicity Risk Assessment Due to Particulate Matter Pollution from Regional Health Data: Case Study from Central Romania.

Air pollution poses one of the greatest dangers to public well-being. This article outlines a study conducted in the Central Romania Region regarding the health risks associated with particulate matter (PM) of two sizes, viz., PM10 and PM2.5. The methodology used consists of the following: (i) an analysis of the effects of PM pollutants, (ii) an analysis of total mortality and cardiovascular-related mortality, and (iii) a general health risk assessment. The Central Region of Romania is situated in the Carpathian Mountains' inner arch (consisting of six counties). The total population of the region under investigation is about 2.6 million inhabitants. Health risk assessment is calculated based on the relative risk (RR) formula. During the study period, our simulations show that reducing these pollutants' concentrations below the new WHO guidelines (2021) will prevent over 172 total fatalities in Brasov alone, as an example. Furthermore, the potential benefit of reducing annual PM2.5 levels on total cardiovascular mortality is around 188 persons in Brasov. Although health benefits may also depend upon other physiological parameters, all general health indicators point towards a significant improvement in overall health by a general reduction in particulate matter, as is shown by the toxicity assessment of the particulate matter in the region of interest. The modality can be applied to other locations for similar studies.

Particulate air pollution and cardiovascular disease mortality in Jiangsu Province, China: a time-series analysis between 2015 and 2021.

Previous time-series studies have revealed a positive association between particulate matter (PM) and acute cardiovascular effects. However, the evidence mostly comes from developed countries and regions, while the majority of air-pollution-related deaths occur in developing countries. To assess the effect of short-term exposure to PM on daily cause-specific cardiovascular disease (CVD) mortality in Jiangsu Province, China, we investigated 1,417,773 CVD deaths from 2015 to 2021 in Jiangsu. The city-specific association was estimated using generalized additive models with quasi-Poisson regression, and then, random effects meta-analysis was performed to estimate the pooled provincial-average associations between acute exposure to PM2.5 and PM10 and cardiovascular disease mortality. To test the independence of PM from gaseous pollutants, we fitted two-pollutant models. Mortality data were also stratified by sex, age, and region to investigate the modification of associations. The exposure-response (E-R) curve from each city was combined using meta-analysis to drive the provincial-level E-R curve. The results showed that each 10-μg/m3 increase in the PM2.5 concentration was associated with a 0.723% [95% confidence interval (CI): 0.512, 0.935] increase in daily total CVD mortality, a 0.669% (95% CI: 0.461, 0.878) increase in CHD mortality, a 0.758% (95% CI: 0.584, 0.931) increase in stroke mortality, a 0.512% (95% CI: 0.245, 0.780) increase in ICH mortality, and a 0.876% (95% CI: 0.637, 1.116) increase in CI mortality. The corresponding increases in daily mortality rates for the same increase in the PM10 concentration were 0.424% (95% CI: 0.293, 0.556), 0.415% (95% CI: 0.228, 0.602), 0.444% (95% CI: 0.330, 0.559), 0.276% (95% CI: 0.026, 0.526), and 0.510% (95% CI: 0.353, 0.667), respectively. The association between PM and total CVD mortality remained significant after adjusting for gaseous pollutants. Females, older adults and districts with lower average PM levels are more sensitive, especially for PM10. The E-R curve for PM on CVD mortality is steeper at lower concentrations and flattens out at higher concentrations. The estimates remained generally consistent in sensitivity analyses when excluding the data during the COVID-19 pandemic period. Our time-series study provides evidence of positive associations between acute exposure to PM2.5 and PM10 and total and cause-specific cardiovascular disease mortality in developing countries.

Trends in Prevalence of Thyroid Dysfunction and its Associations With Mortality Among US Participants, 1988-2012.

Various dynamic factors could influence the prevalence and distribution of thyroid dysfunction. To provide national estimates and temporal trends in prevalence of thyroid dysfunction over the past 3 decades in United States and determine the impact of thyroid dysfunction on mortality in US adults. A cross-sectional analysis of data from 33 117 participants aged 12 years or older in the National Health and Nutrition Examination Survey III (1988-1994), 1999-2002, and 2007-2012. The weighted mean age was 41.6 years, and 48.3% were men. In 2007 through 2012, the prevalence of subclinical and overt hypothyroidism, subclinical and overt hyperthyroidism was 4.3%, 0.33%, 3.2%, and 0.2% respectively. Eighty percent of individuals with thyroid dysfunction were previously undiagnosed. The prevalence of subclinical hypothyroidism and hyperthyroidism was stable, whereas overt hypothyroidism (0.54% [95% CI, 0.35-0.8] vs 0.33% [95% CI, 0.23-0.48]) and hyperthyroidism (0.8% [95% CI, 0.58-1.1] vs 0.2% [95% CI, 0.12-0.33]) were less prevalent in 2007-2012 compared to 1988-1994. Older age, White Americans, obesity, and positivity for thyroid peroxidase antibody and thyroglobulin antibody were risk factors for hypothyroidism, whereas older age, women, and Black Americans were risk factors for hyperthyroidism. Over a median follow-up of 17.2 years, no significant association was observed between any type of thyroid dysfunction with the risk of total or cardiovascular mortality. However, among individuals aged 65 years or older, subclinical hypothyroidism was associated with a higher risk of total mortality (hazard ratio, 1.17; 95% CI, 1.00-1.37; P = .05) and cardiovascular mortality (HR, 1.29; 95% CI, 1.04-1.62; P = .02). The prevalence of subclinical thyroid dysfunction remained relatively unchanged, whereas that of overt thyroid dysfunction decreased. Subclinical hypothyroidism was associated with a higher mortality among individuals aged 65 years or older.

Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis.

Despite the fact that several studies have investigated the association between serum copper levels (S-Cu) and the risk of cardiovascular diseases, this relationship remains unclear. The aims of this study were to investigate the association between S-Cu and risk of major adverse cardiovascular events (MACE), including total stroke, ischemic stroke, hemorrhagic stroke, myocardial infarction and cardiovascular mortality, and identify potential sources of results heterogeneity. We carried out a systematic review and meta-analysis. The selection criteria were: (1) Observational studies (cohort studies, case-control studies and hybrid studies); (2) Studies containing quantitative data about the relationship between S-Cu and risk of MACE; (3) Estimating association measures; and (4) Studies written in English, French or Spanish. Overall pooled Odds ratio (pOR) and 95% confidence intervals (95% CI) of MACE for the highest vs. lowest S-Cu category were calculated using random-effects models. Sixteen studies with a total of 41,322 participants were included in the meta-analysis: 10 prospective cohort studies, 5 nested case-control studies and 1 case-control study. Comparing highest vs. lowest category, high S-Cu levels were associated with total stroke (pOR: 1.49, 95% CI 1.22-1.82; I2 = 0%, p = 0.54), myocardial infarction (pOR: 1.31, 95% CI 1.17-1.46; I2 = 0.0%, p = 0.92) and cardiovascular mortality (pOR: 1.60, 95% CI 1.39-1.86; I2 = 0.0%, p = 0.54). Subgroup analysis showed that studies with a hybrid design had higher risks for cardiovascular mortality (pOR: 3.42, 95% CI 1.98-5.92) and ischemic stroke (pOR: 1.54, 95% CI 1.30-1.83). High S-Cu levels were associated with an increased risk of total stroke, myocardial infarction and cardiovascular mortality. Hybrid studies seems to modify the strength of the association between S-Cu and the risk of cardiovascular mortality and ischemic stroke. [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370782], identifier [CRD42022370782].

1350-P: Risk Models for the Development of Cardiovascular and Microvascular Events in Adults with Type 2 Diabetes in the FIELD Study

Background: There are a few prediction models for chronic complications in people with type 2 diabetes (T2D). This study developed such risk models. Methods: Data from 9795 adults with T2D in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial were used to develop risk prediction models for total CVD events, cardiovascular mortality, amputations and new microvascular events using 27 candidate traditional risk factors and additional novel biomarkers (incl. vascular and systemic inflammation, oxidative stress; n=26) using exhaustive search methods. Results: There were 1295 total first CVD events, 267 CVD deaths, 115 amputations and 1530 new microvascular events. A total of 19 and 18 traditional risk factors were selected in the clinical risk models for total CVD events and CVD mortality, with AUC of 0.723 and 0.821 respectively. For individual microvascular complications, the AUC of their models ranged from 0.656 to 0.895. The addition of novel biomarkers to the clinical risk models only resulted in modestly higher AUC (Table below). Conclusion: New clinical risk models can be implemented as risk prediction tools for chronic complications in adults with T2D, including for sight-threatening retinopathy and amputations. Novel biomarkers may guide future research on disease mechanisms, but had limited predictive value over clinical variables. Disclosure K.Ong: None. M.Taskinen: Board Member; Novo Nordisk, Consultant; Eli Lilly and Company, Novartis, Akcea, Research Support; Novo Nordisk. R.J.Simes: None. A.Jenkins: Advisory Panel; Insulet Corporation, Board Member; Insulin for Life, Research Support; Abbott Diabetes, Medtronic, Hemsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), National Institutes of Health. A.C.Keech: None. On behalf of the field study investigators: n/a. R.L.O'connell: None. A.S.Januszewski: None. M.W.Donoghoe: None. V.Gebski: None. D.Sullivan: None. K.Rye: None. R.S.Scott: None. J.D.Best: None. Funding Laboratories Fournier; National Health and Medical Research Council of Australia (457103, 1024105, 1037786)

PROGNOSIS OF RESISTANT HYPERTENSION, WHITE-COAT RESISTANT HYPERTENSION, AND REFRACTORY HYPERTENSION

Objective: To evaluate total and cardiovascular mortality in different forms of Resistant Hypertension (RH). Design and method: A total of 35129 treated patients were included from the Spanish ABPM Registry. Mean follow-up was 10 years. Total and cardiovascular mortality were compared in Cox models adjusted for clinical confounders. The following groups were compared: - Controlled Hypertension (CH; N = 8146; 23.2%): normal office BP treated with 3 or less antihypertensive drugs vs. RH (N = 9408; 26.8%): elevated office BP treated with 3 or more drugs or normal office BP treated with 4 or more drugs. - Controlled RH (CRH; N = 831; 8.8%): normal office BP treated with 4 or more drugs vs. Uncontrolled RH (UCRH; 8577; 91.2%): elevated office BP treated with 3 or more drugs. - Among patients with UCRH, the following groups were compared: True RH (TRH; 5288; 61.7%): elevated (&gt;130/80 mmHg) 24-h BP vs. White-coat RH (WCRH; 3289; 38.3%): normal 24-h BP. - Refractory hypertension (RefrH; 823; 8.7%): elevated office BP while treated with 5 or more drugs vs. Non-refractory RH (the remaining RH patients). Results: Compared to CH, RH was associated with an increased risk in total mortality (HR: 1.22; 95%CI: 1.13 - 1.31) and cardiovascular mortality (1.37; 1.21 - 1.55). Compared with CRH, UCRH was not associated with a significant increased risk in total or cardiovascular mortality. Compared to WCRH, TRH increased the risk of mortality (1.45; 1.32 - 1.60) and cardiovascular mortality (1.68 (1.43 - 1.98). Finally, RefrH also increased the risk of total mortality (1.16; 1.01 - 1.34) and cardiovascular mortality (1.30; 1.05 - 1.62) in comparison to non-refractory RH. Either total or cardiovascular mortality was not increased in WCRH, compared to CH. Conclusions: RH increased the risk of total and mortality with respect to CH. Among RH, office BP control does not modify such prognosis, while 24-h BP is a powerful determinant, with a clear increased risk in those with elevated 24-h BP (TRH), compared to those with normal 24-h BP (WCRH). The study confirms the clinical importance of RH, as well as the usefulness of ABPM in stratifying those patients, in order to improve therapeutical efforts to reduce the global risk.

EFFICACY OF BETA-BLOCKERS ON BLOOD PRESSURE CONTROL, MORBIDITY AND MORTALITY ENDPOINTS IN HYPERTENSIVES OF AFRICAN ANCESTRY: AN INDIVIDUAL PATIENT DATA META-ANALYSIS

Objective: Beta-blockers have been reported to sub-optimally lower central aortic blood pressure and cause an increased stroke incidence. There is a paucity of data regarding beta-blocker efficacy in patients of African origin. We proposed that an individual patient data meta-analysis (IPD-MA) focusing on the efficacy of traditional and second or third-generation beta-blockers (STGBBs) in the whole and African hypertensive population may provide new insights. Design and method: A single-stage IPD-MA analysed the efficacy of STGBBs in the setting of other anti-hypertensives for lowering mean arterial pressure (MAP) and reducing the occurrence of composite outcome (total cardiovascular mortality, stroke and myocardial infarction). Results: A total of 11860 participants were included in the analysis, of which 3864 (32.5%) were on STGBB. STGBBs reduced the MAP by 1.75 mmHg (95% confidence interval (CI): 1.16 - 2.33; p&lt;0.001) in the whole population and by 1.93 mmHg (95% CI: 0.86 - 3.00; p&lt;0.001) in 3880 African hypertensives, outperforming angiotensin-converting enzyme inhibitors (ACE-I) in the whole population studied and ACE-I and calcium channel blockers in the African population. Confounding through beta-blocker use in established cardiovascular disease resulted in STGBBs being associated with an adjusted odds ratio of 1.33 (95 % CI: 1.06 - 1.65; p = 0.015) of the composite outcome while controlling for age, gender, race and smoking history. STGBBs were not associated with an increase in the odds of stroke in African hypertensives nor the whole population. Conclusions: STGBBs reduced the MAP comparably to other anti-hypertensives. No increase in the odds of stroke was found.

Blood pressure targets for the treatment of people with hypertension and cardiovascular disease.

This is the third update of the review first published in 2017. Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure to below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown. To determine if lower blood pressure targets (systolic/diastolic 135/85 mmHg or less) are associated with reduction in mortality and morbidity compared with standard blood pressure targets (140 mmHg to 160mmHg/90 mmHg to 100 mmHg or less) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease). For this updated review, we used standard, extensive Cochrane search methods. The latest search date was January 2022. We applied no language restrictions. We included randomized controlled trials (RCTs) with more than 50 participants per group that provided at least six months' follow-up. Trial reports had to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions involved lower targets for systolic/diastolic blood pressure (135/85 mmHg or less) compared with standard targets for blood pressure (140 mmHg to 160 mmHg/90 mmHg to 100 mmHg or less). Participants were adults with documented hypertension and adults receiving treatment for hypertension with a cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease, or angina pectoris. We used standard Cochrane methods. We used GRADE to assess the certainty of the evidence. We included seven RCTs that involved 9595 participants. Mean follow-up was 3.7 years (range 1.0 to 4.7 years). Six of seven RCTs provided individual participant data. None of the included studies was blinded to participants or clinicians because of the need to titrate antihypertensive drugs to reach a specific blood pressure goal. However, an independent committee blinded to group allocation assessed clinical events in all trials. Hence, we assessed all trials at high risk of performance bias and low risk of detection bias. We also considered other issues, such as early termination of studies and subgroups of participants not predefined, to downgrade the certainty of the evidence. We found there is probably little to no difference in total mortality (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.91 to 1.23; 7 studies, 9595 participants; moderate-certainty evidence) or cardiovascular mortality (RR 1.03, 95% CI 0.82 to 1.29; 6 studies, 9484 participants; moderate-certainty evidence). Similarly, we found there may be little to no differences in serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 7 studies, 9595 participants; low-certainty evidence) or total cardiovascular events (including myocardial infarction, stroke, sudden death, hospitalization, or death from congestive heart failure (CHF)) (RR 0.89, 95% CI 0.80 to 1.00; 7 studies, 9595 participants; low-certainty evidence). The evidence was very uncertain about withdrawals due to adverse effects. However, studies suggest more participants may withdraw due to adverse effects in the lower target group (RR 8.16, 95% CI 2.06 to 32.28; 3 studies, 801 participants; very low-certainty evidence). Systolic and diastolic blood pressure readings were lower in the lower target group (systolic: mean difference (MD) -8.77 mmHg, 95% CI -12.82 to -4.73; 7 studies, 8657 participants; diastolic: MD -4.50 mmHg, 95% CI -6.35 to -2.65; 6 studies, 8546 participants). More drugs were needed in the lower target group (MD 0.56, 95% CI 0.16 to 0.96; 5 studies, 7910 participants), but blood pressure targets at one year were achieved more frequently in the standard target group (RR 1.20, 95% CI 1.17 to 1.23; 7 studies, 8699 participants). We found there is probably little to no difference in total mortality and cardiovascular mortality between people with hypertension and cardiovascular disease treated to a lower compared to a standard blood pressure target. There may also be little to no difference in serious adverse events or total cardiovascular events. This suggests that no net health benefit is derived from a lower systolic blood pressure target. We found very limited evidence on withdrawals due to adverse effects, which led to high uncertainty. At present, evidence is insufficient to justify lower blood pressure targets (135/85 mmHg or less) in people with hypertension and established cardiovascular disease. Several trials are still ongoing, which may provide an important input to this topic in the near future.

Prognostic impact of the serial change of a systemic inflammation-nutrition index in patients with heart failure with preserved ejection fraction: insights from pursuit-hfpef registry

Abstract Background Malnutrition and inflammation are associated with poor outcomes with heart failure (HF). It has been reported that advanced lung cancer inflammation index (ALI), calculated by body mass index × serum albumin level / neutrophil to lymphocyte ratio (NLR) can be useful for the risk stratification and predicting the post-discharge prognosis of the patients with acute decompensated heart failure (ADHF). However, there is no information available on the prognostic value of the serial ALI change in ADHF patients with preserved ejection fraction (HFpEF). Methods and results Patients' data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, which is a prospective multicenter observational registry for ADHF-HFpEF in Osaka. Laboratory data and body weight measurements were performed at the discharge and 1 year after the discharge. We analyzed 527 patients after exclusion of patients on dialysis, in-hospital death, missing follow-up data, or missing data to calculate ALI. The study patients were categorized by the serial change from baseline to 1 year after the discharge (ΔALI) as follows: low tertile: ΔALI &amp;lt;−6.99 (n=176), middle tertile: −6.99 ≤ ALI &amp;lt;8.44 (n=176), and high tertile: 8.44 ≤ ΔALI (n=175). The endpoints of the present study were all-cause death (ACD) and cardiovascular death (CVD). During a mean follow-up period of 1.5±1.0 years, 94 patients had ACD and 40 patients had CVD. The Kaplan-Meier analysis revealed that the patients with middle and low ΔALI at 1 year after heart failure hospitalization had a significantly greater risk of reaching the ACD and CVD than those with high ΔALI (ACD: 22% vs 22% vs 10%, p=0.0011, CVD: 10% vs 9% vs 3%, p=0.014). On multivariate Cox analysis, ΔALI was significantly associated with ACD independently of age, gender, serum NT-proBNP level, and baseline ALI after adjustment for NYHA functional class, serum creatinine level, serum hemoglobin level, serum CRP level, serum sodium level and LVEF. Conclusion This study showed that patients with the increased ALI after the discharge had improved outcome in comparison to those without the increased ALI. The serial change of ALI, a systemic inflammation-nutrition index, might be useful for stratifying ADHF patients with HFpEF at risk for the total mortality and cardiovascular mortality. Funding Acknowledgement Type of funding sources: None.

Future temperature-related mortality considering physiological and socioeconomic adaptation: a modelling framework

As the climate changes, it is crucial to focus not only on mitigation measures but also on building climate change resilience by developing efficient adaptation strategies. Although population adaptation is a major determinant of future climate-related health burden, it is not well accounted for in studies that project the health impact of climate change. We propose a methodological framework for temperature-related mortality that incorporates two simultaneous adaptation-sensitivity pathways: the physiological pathway, considering both heat adaptation and cold sensitivity, and the socioeconomic pathway, which is influenced by changes in future adaptive capacities. To demonstrate its utility we apply the framework to a case study mortality time-series dataset from Bavaria, Germany. In this modelling framework, we used extrapolated location-specific and age-specific baseline exposure-response functions and propose different future scenarios of cold sensitivity and heat adaptation on the basis of varying slopes of these exposure-response functions. We also incorporated future socioeconomic adaptation in the exposure-response functions using projections of gross domestic product under the respective shared socioeconomic pathways. Future adaptable fractions, representing the deaths avoided under each of the future scenarios, are projected under combinations of two climate change scenarios (shared socioeconomic pathway [SSP]1-2.6 and SSP3-7.0) and the respective plausible population projection scenarios (SSP1 and SSP3), also incorporating the future changes in demographic age structure and mortality. The case study for this framework was done for five districts in Bavaria, for both total non-accidental mortality and cardiovascular disease mortality. The baseline data was obtained for the period 1990-2006, and the future period was defined as 2083-99. In our Bavaria case study, average temperature was projected to increase by 2099 by an average of 1·1°C under SSP1-2.6 and by 4·1°C under SSP3-7.0. We observed the adaptable fraction to be largely influenced by socioeconomic adaptation for both total mortality and cardiovascular disease mortality, and for both climate change scenarios. For example, for total mortality, the highest adaptable fraction of 18·56% (95% empirical CI 10·77-23·67) was observed under the SSP1-2.6 future scenario, in the presence of socioeconomic adaptation and under the highest heat adaptation (10%) provided the cold sensitivity remains 0%. The cold adaptable fraction is lower than the heat adaptable fraction under all scenarios. In the absence of socioeconomic adaptation, population ageing will lead to higher temperature-related mortality. Our developed framework helps to systematically understand the effectiveness of adaptation mechanisms. In the future, socioeconomic adaptation is estimated to play a major role in determining temperature-related excess mortality. Furthermore, cold sensitivity might outweigh heat adaptation in the majority of locations worldwide. Similarly, population ageing is projected to continue to determine future temperature-related mortality. EU Horizon 2020 (EXHAUSTION).

Association of short-term exposure to ambient PM1 with total and cause-specific cardiovascular disease mortality

BACKGROUND AND AIM: The acute effects of exposure to ambient particulate matter with an aerodynamic diameter &amp;#x2264;1 &amp;#x3bc;m (PM1) on cardiovascular disease (CVD) mortality remain poorly understood. We aimed to investigate the association of short-term exposure to ambient PM1 with total and cause-specific CVD mortality, and estimate the corresponding excess mortality. METHODS: Using the Jiangsu provincial mortality surveillance system, we conducted a time-stratified case-crossover study among 988 446 CVD deaths in Jiangsu province, China during 2015-2019. Daily residential PM1 exposures for each subject was assessed using a validated grid data. Conditional logistic regression models integrated with distributed lag linear or nonlinear models were performed to conduct exposure-response analyses. RESULTS: Each 10 &amp;#x3bc;g/m3 increase of PM1 exposure during the same day of CVD death and 1 day prior was significantly associated with a 1.46% (95% confidence interval [CI]: 1.27%, 1.66%), 1.46% (0.15%, 2.78%), 1.93% (1.24%, 2.64%), 1.25% (0.93%, 1.57%), 1.37% (1.07%, 1.66%), and 1.71% (1.22%, 2.21%) increase in odds of mortality from total CVDs, chronic rheumatic heart diseases (CRHD), hypertensive diseases, ischemic heart diseases (IHD), stroke, and sequelae of stroke, respectively. The excess fraction of total CVD mortality attributable to PM1 exposure was 5.72%, while the cause-specific excess fractions ranged from 5.34% for IHD to 8.25% for CRHD. Significantly higher associations and excess fractions were identified for mortality from total and/or certain cause-specific CVDs in adults 80 years or older. CONCLUSIONS: Short-term exposure to ambient PM1 was associated with increased risk of total and cause-specific CVD mortality, which may lead to a considerable excess mortality especially among older adults. Our findings highlight a potential approach to prevent premature deaths from CVDs by reducing ambient PM1 exposures and provide essential quantitative data for the formulation of future air quality standards for ambient PM1. KEYWORDS: Cardiovascular diseases; PM1; Mortality; DLM; DLNM; Case-crossover study.

Association of short-term exposure to ambient PM1 with total and cause-specific cardiovascular disease mortality

BackgroundThe acute effects of exposure to ambient particulate matter with an aerodynamic diameter ≤1 μm (PM1) on cardiovascular disease (CVD) mortality remain unclear. ObjectivesTo investigate whether short-term exposure to ambient PM1 was associated with mortality from total and/or cause-specific CVDs, and estimate the excess mortality. MethodsA time-stratified case-crossover study was conducted among 1,081,507 CVD deaths in Jiangsu province, China from 2015 to 2020. We assessed daily residential ambient PM1 exposures using a validated grid dataset for each subject. Conditional logistic regression models and distributed lag linear or nonlinear models were employed to quantify the association of PM1 exposure with mortality during the same day of CVD death and 1 day prior. ResultsEach 10 μg/m3 increase of PM1 exposure was significantly associated with a 1.46 % (95 % confidence interval: 1.28 %, 1.65 %), 1.95 % (1.28 %, 2.63 %), 1.16 % (0.86 %, 1.47 %), 1.41 % (1.13 %, 1.69 %), and 1.83 % (1.37 %, 2.30 %) increased odds of mortality from total CVDs, hypertensive diseases (HDs), ischemic heart diseases (IHDs), stroke, and sequelae of stroke, respectively (all p <0.05). No significant association was identified with mortality from pulmonary heart disease or chronic rheumatic heart diseases. The excess fraction of total CVD mortality attributable to PM1 exposure was 5.71 %, while the cause-specific excess fractions ranged from 4.98 % for IHDs to 7.46 % for HDs. Significantly higher excess fractions were observed for total and certain cause-specific CVD mortality in adults 80 years or older. ConclusionsWe found that short-term exposure to ambient PM1 was significantly associated with an increased odds of mortality from total and specific CVDs and may lead to considerable excess mortality especially among older adults. Our findings highlight a potential approach to prevent premature CVD deaths by reducing PM1 exposures and provide essential quantitative data for the development of future air quality standards for ambient PM1.

Effects of Empagliflozin in Women and Men With Heart Failure and Preserved Ejection Fraction.

Background:Women and men with heart failure (HF) and preserved ejection fraction may differ in their clinical characteristics and their response to therapy. The aim of this study was to evaluate the influence of sex on the effects of empagliflozin in patients with HF and preserved ejection fraction enrolled in the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction).Methods:The effects of empagliflozin on the primary outcome of cardiovascular death or hospitalization for HF and on secondary outcomes (including total HF hospitalization, cardiovascular and all-cause mortality, and Kansas City Cardiomyopathy Questionnaire scores) were compared in women and men in the overall cohort and in subgroups defined by left ventricular ejection fraction (41%–49%, 50%–59%, and ≥60%). The effects of empagliflozin on physiological measures, including changes in systolic blood pressure, uric acid, hemoglobin, body weight, and natriuretic peptide levels, were also assessed.Results:Of the 5988 patients randomized, 2676 (44.7%) were women. In the placebo arm, women tended to have lower risk for adverse outcomes, including a lower risk of all-cause mortality (hazard ratio, 0.69 [95% CI, 0.56, 0.84]). Compared with placebo, empagliflozin reduced the risk of cardiovascular death or hospitalization for HF to a similar degree in both sexes (hazard ratio, 0.81 [95% CI, 0.69, 0.96] for men; and hazard ratio, 0.75 [95% CI, 0.61, 0.92] for women; Pinteraction=0.54). Sex did not modify the relationship between empagliflozin and outcomes across ejection fraction groups. Similar results were seen for secondary outcomes and physiological measures. Compared with placebo, empagliflozin improved the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score to a similar extent in both sexes (1.38 for men versus 1.63 for women at 52 weeks; Pinteraction=0.77); the results were similar for Kansas City Cardiomyopathy Questionnaire overall summary score and total summary score.Conclusions:Empagliflozin produced similar benefits on outcomes and health status in women and men with HF and preserved ejection fraction.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057951.