Greater Risk Of Cardiovascular Mortality Research Articles

Effect of Heat Exposure on Inflammation and Platelet Activity in Adults with Heart Disease

INTRODUCTION: Extreme heat events are associated with a greater risk of cardiovascular mortality, especially in adults with pre-existing heart disease. The pathophysiological mechanisms mediating these relationships remain unknown. One proposed mechanism, supported by pre-clinical studies employing heat stroke models of severe body hyperthermia, is that heat exposure causes an inflammatory response leading to platelet activation and clot formation. It remains unknown if milder body hyperthermia, such as the one experienced during exposure to a hot environment, elicits an inflammatory response and/or increases platelet activity in adults living with heart disease.OBJECTIVES & HYPTOHESES: To assess whether exposure to a hot and humid environment (1) increases circulating concentrations of inflammatory cytokines and (2) induces platelet activation in adults with heart disease.METHODOLOGY: Adults living with coronary artery disease (67±8 years; 13M/2F) sat within a climate chamber maintained at 38°C and 50% humidity for 3h. Core (rectal) and skin temperatures were measured continuously. Blood samples were drawn before and 2.5h into heat exposure. The blood samples were analyzed for IL-6, IL-8, IL-18, TNFα and IL-1β (multiplexed bead-based immunoassay). Platelet aggregation was measured by impedance (Multiplate assay) induced with ADP (6.5 μM), TRAP (15 μM) and collagen (1.5 μg/ml). The total-thrombus analysis system (T-TAS, PL-CHIP) was used to measure thrombus onset time and total thrombogenicity.RESULTS: Core and skin temperatures increased by 0.35 ± 0.24°C and 4.85 ± 0.84°C, respectively (p<0.05). There were no changes (Δpost-pre) in IL-6 (0.31 ± 1.91 pg/ml, p=0.60), IL-18 (-10.29 ± 21.01 pg/ml, p=0.16), IL-8 (1.10 ± 2.39 pg/ml, p=0.18), TNFα (-1.12 ± 4.10 pg/ml, p =0.39), or IL-1β (0.53 ± 2.36 pg/ml, p=0.48) during heat exposure. Moreover, heat exposure did not increase platelet activation in response to ADP (-8.31 ± 33.70 U, p=0.34), TRAP (16.19 ± 36.54 U, p=0.10), or collagen (-9.19 ± 30.31 U, p=0.24). Lastly, there was no change in thrombus onset time (2.18 ± 37.31 s, p=0.850) or total thrombogenicity (2.8 ± 168.7 PL-AUC, p=0.90).CONCLUSION: These results suggest that inflammation predisposing to thrombus formation may not contribute to the greater cardiac risk associated with short-term exposure to humid heat. Canadian Institutes for Health Research. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Vitamin D Deficiency, Inflammation, and Diminished Endogenous Regenerative Capacity in Coronary Heart Disease

BackgroundVitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in and may promote greater risk through inflammation and impaired progenitor cell function. ObjectivesThe authors examined VDD, high-sensitivity C-reactive protein (hsCRP), circulating progenitor cell (CPC) counts, and outcomes in patients with CHD. They hypothesized that the higher risk with VDD is mediated by inflammation and impaired regenerative capacity. MethodsA total of 5,452 individuals with CHD in the Emory Cardiovascular Biobank had measurement of 25-hydroxyvitamin D, subsets of whom had hsCRP measurements and CPCs estimated as CD34-expressing mononuclear cell counts. Findings were validated in an independent cohort. 25-hydroxyvitamin D <20 ng/mL was considered VDD. Cox and Fine-Gray models determined associations between marker levels and: 1) all-cause mortality; 2) cardiovascular mortality; and 3) major adverse cardiovascular events, a composite of adverse CHD outcomes. ResultsVDD (43.6% of individuals) was associated with higher adjusted cardiovascular mortality (HR: 1.57, 95% CI: 1.09-2.28). There were significant interactions between VDD and hsCRP and CPC counts in predicting cardiovascular mortality. Individuals with both VDD and elevated hsCRP had the greatest risk (HR: 2.82, 95% CI: 2.16-3.67). Only individuals with both VDD and low CPC counts were at high risk (HR: 2.25, 95% CI: 1.46-3.46). These findings were reproduced in the validation cohort. ConclusionsVDD predicts adverse outcomes in CHD. Those with VDD, inflammation and/or diminished regenerative capacity are at a significantly greater risk of cardiovascular mortality. Whether targeted supplementation in these high-risk groups improves risk warrants further study.

Comparison of Cardiovascular Disease Risk Indicators in Bipolar Disorder Patients with Healthy Controls

Aim: It is important to assess the likelihood of cardiovascular disease in patients with bipolar disorder (BD). In this study, indicators of increased cardiovascular disease risk on electrocardiogram (ECG) and laboratory were evaluated. Material and Methods: In the present investigation, we studied the demographic details, ECG variables, and blood test results of 90 healthy controls (HC) and 97 patients we followed for BD diagnosis. Results: Age and gender trends were similar between the BD and HC groups (p=0.844 and p=0.664). BD had a higher mean number of fragmented QRS (fQRS) than the HC group, and fQRS was more frequent (p=0.002 and p=0.007). The frontal QRS-T angle was wider in the BD group than it was in the HC group (p=0.038). Monocyte-to-lymphocyte ratio (MLR), monocytes to high-density lipoprotein cholesterol (HDL-C) ratio (MHR), and atherogenic index of plasma (AIP) were statistically greater in BD patients (p=0.021, p&amp;lt;0.001, and p&amp;lt;0.001). Conclusion: In brief, the report indicates that impaired ventricular repolarization is related to an elevation in the frontal QRS-T angle in BD. As a result, BD patients have a greater risk of cardiovascular mortality and ventricular arrhythmias. As a result, clinicians ought to have a greater understanding of the frontal QRS-T angle and conduct an ECG examination on regular controls.

Sex-specific associations of cardiorespiratory fitness and galectin-3 in the general population.

Low cardiorespiratory fitness (CRF) is associated with greater mortality and morbidity. Galectin-3 (Gal-3) is a prognostic biomarker for fibrosis and heart failure. Gal-3 is also associated with a greater risk for cardiovascular mortality. Whether CRF is related with Gal-3 is unclear. The objective of this study was to assess the sex-specific associations of CRF and Gal-3 levels in the general population. Gal-3 concentrations were determined using a sandwich enzyme immunoassay in the population-based Study of Health in Pomerania (SHIP-TREND-0). Sex-stratified linear regression models adjusted for age, current smoking status, and renal function were used. Individuals with left ventricular ejection fraction (LVEF) <40%, previous myocardial infarction, atrial fibrillation, chronic lung disease, severe renal disease (estimated glomerular filtration rate <30mL/min/mm2 ), a history of cancer, and extreme values for Gal-3 (<1st percentile; >99th percentile) were excluded. A total of n=1515 participants with a median age of 49 (IQR: 39-60years, 48% males) were included. In men, a 1L/min greater VO2 peak was significantly related to 0.50ng/mL (95% CI -0.8068 to -0.1938, P<0.01) less Gal-3. In males, a 1mL/min/kg higher VO2 peak adjusted for body weight was associated with -0.0286ng/mL (95% CI -0.0052 to -0.0005, P=0.02) less Gal-3. When VO2 peak was adjusted for lean mass 1mL/kg/min more was correlated with a -0.0022ng/mL (95% CI -0.0043 to -0.0007, P=0.04) less Gal-3. In women, VO2 peak (β -0.2046 95% CI -0.6541 to 0.2449, P=0.37) and VO2 peak adjusted for lean mass (β -0.0019 95% CI -0.0421 to -0.0050, P=0.12) were not related with Gal-3, whereas a 1mL/min/kg higher VO2 peak adjusted for body weight was significantly associated with a -0.0064ng/mL lower Gal-3 (95% CI -0.0092 to -0.0035, P<0.01). There were no differences between pre-menopausal and post-menopausal women. VO2 peak was associated with Gal-3 only in men, but VO2 peak adjusted for body weight in women and men. Our results suggest that the adverse consequences of low CRF may be mediated by Gal-3. Further research is needed to understand the sex-specific association between CRF and Gal-3 and whether they are clinically relevant.

Liver fibrosis scores and prognosis in patients with cardiovascular diseases: A systematic review and meta-analysis.

In patients with nonalcoholic fatty liver disease, liver fibrosis was associated with a higher risk of cardiovascular events. However, the relationship between liver fibrosis scores and clinical outcomes in patients with cardiovascular disease remains unclear. Searching from PubMed, EMBASE and Cochrane Library databases yielded cohort studies that reported adjusted effect size between liver fibrosis scores (Fibrosis-4 score [FIB-4] or NAFLD fibrosis score [NFS]) and prognosis in patients with cardiovascular disease. The effect size was computed using a random-effects model. This meta-analysis included twelve cohort studies involving 25,252 patients with cardiovascular disease. Participants with the highest baseline level of FIB-4 or NFS had a significantly increased risk of cardiovascular events (FIB-4, HR: 1.75, 95% CI: 1.53-2.00, I 2 = 0%; NFS, HR: 1.92, 95% CI: 1.50-2.47, I 2 =47%). This finding was consistent with the analysis of FIB-4 or NFS as a continuous variable (per 1-unit increment FIB-4, HR: 1.15, 95% CI: 1.06-1.24, I 2 = 72%; NFS, HR: 1.15, 95% CI: 1.07-1.24, I 2 = 71%). Furthermore, participants with the highest levels of FIB-4 or NFS had a greater risk of cardiovascular mortality (FIB-4, HR: 2.07, 95% CI: 1.19-3.61, I 2 =89%; NFS, HR: 3.72, 95% CI: 2.62-5.29, I 2 =60%) and all-cause mortality (FIB-4, HR: 1.81, 95% CI: 1.24-2.66, I 2 =90%; NFS, HR: 3.49, 95% CI: 2.82-4.31, I 2 =25%). This result was also consistent as a continuous variable. Higher levels of FIB-4 and NFS are related to an increased risk of cardiovascular events, cardiovascular mortality and all-cause mortality in patients with cardiovascular disease.

Cardiovascular events in insomnia patients with post-traumatic stress disorder

BackgroundBoth post-traumatic stress disorder (PTSD) and insomnia are independently associated with a greater risk of cardiovascular mortality. The objective of this study is to determine whether PTSD plus insomnia is associated with a higher risk of major adverse cardiovascular events (MACEs) than either condition alone in a large cohort of veterans. MethodsWe conducted a retrospective analysis of the national Veterans Health Administration (VHA) electronic medical records covering veterans 18 years or older with the diagnosis of PTSD, insomnia, or both from January 1, 2015, to December 31, 2020. MACE was defined as new-onset myocardial infarction (MI), transient ischemic attack (TIA) or stroke, based on ICD-9 and ICD-10 diagnosis codes from inpatient or outpatient encounters. ResultsA total of 19,080 veterans, 1840 with PTSD plus insomnia and 17,240 with either PTSD or insomnia, were included in the analysis. Baseline mean (SD) age was 46.3 (11.5) years. During median follow-up of 3.9 (interquartile range, 2.4–5.1) years, 206 (1%) veterans developed incident MACE. Cumulative incidence for MI, TIA and/or stroke was larger in veterans with PTSD plus insomnia compared to PTSD and insomnia alone (p=0.008). In a Cox proportional hazards model, PTSD plus insomnia was significantly associated with greater risk of developing MACEs (hazard ratio [HR], 1.44; 95% CI, 1.38–1.50, p=0.01) than either condition after adjusting for multiple covariates including age, gender, smoking, hypertension, depression, and burden of comorbidities. ConclusionsThis cohort study found that PTSD plus insomnia is a risk factor for MACEs of greater magnitude than PTSD- or insomnia-alone.

Effects of passive heat exposure on myocardial blood flow in healthy young and older adults

INTRODUCTIONExtreme heat is associated with a greater risk of cardiovascular mortality in older adults (≥60 years). However, the pathophysiology that links extreme heat and cardiovascular mortality remains unknown. One possibility is that myocardial oxygen requirements during heat exposure cannot be met by sufficient increased in myocardial blood flow (MBF) thereby predisposing to ischemia. However, the extent to which MBF increases during heat exposure, and whether age alters this increase, is unknown. The objective of this study was to test the hypothesis that passive heat exposure increases MBF and that this increase is attenuated in healthy older adults.METHODSMBF was measured during passive heat exposure (water‐perfused suit) in 15 young (27 years, range: 24‐30) and 14 older (68 years, range: 64‐72) healthy adults with 82‐Rubidium positron emission tomography. Four MBF measurements were performed: prior to heat exposure (baseline) and at an increase in rectal temperature of 0.5°C, 1.0°C, and 1.5°C. Heart rate (ECG) and blood pressure (automated auscultation) were also measured to calculate rate pressure product (RPP; heart rate x systolic blood pressure). MBF reserve (MFR) was calculated by dividing the MBF at 1.5°C by baseline MBF.RESULTSBaseline MBF was 0.76 ± 0.19 mL/min/g in young adults and 0.88 ± 0.21 mL/min/g in older adults (p=0.14). MBF increased similarly in both groups during heat exposure (interaction, p=0.31). Nonetheless, older adults displayed a lower MFR at an increase in rectal temperature of 1.5°C (young: 2.3 ± 0.7 vs. older: 1.8 ± 0.4, p=0.03). The lower MFR in older adults was paralleled by an attenuated increase in RPP during passive heating (at + 1.5°C, young: 6.8 ± 1.7vs. older: 3.6 ± 2.2 bpm·mmHg·103, p&lt;0.01), due to a blunted increase in heart rate (young: 50 ± 12vs. older: 34 ± 14 bpm, p&lt;0.01). When the change in MBF was plotted against the change in RPP, the slope of the regression lines did not differ between young (0.11 [95% CI; 0.07, 0.15]) and older (0.08 [95% CI; 0.04, 0.11] mL/g/min/ bpm·mmHg·103,p=0.24) adults.CONCLUSIONThese results show that passive heat exposure roughly doubles MBF in healthy young and older adults. Furthermore, the results demonstrate that the increase in MBF during passive heat exposure is not altered by age and is proportional to the increase in RPP.

Thoracic Aortic Diameter and Cardiovascular Events and Mortality among Women and Men.

Background Thoracic aortic diameter may have a role as a biomarker for major adverse cardiovascular events. Purpose To evaluate the sex-specific association of the diameters of the ascending (AA) and descending (DA) thoracic aorta with risk of stroke, coronary heart disease, heart failure, cardiovascular mortality, and all-cause mortality. Materials and Methods Study participants from the population-based Rotterdam Study who underwent multidetector-row CT between 2003 and 2006 were evaluated. Cox proportional hazard models were conducted to evaluate the associations of AA and DA diameters indexed and not indexed for body mass index (BMI) with cardiovascular events and mortality for men and women. Hazard ratios (HRs) were calculated per 1-unit greater SD of aortic diameters. Results A total of 2178 participants (mean age, 69 years; 55% women) were included. Mean follow-up was 9 years. Each 0.23-mm/(kg/m2) larger BMI-indexed AA diameter was associated with a 33% higher cardiovascular mortality risk in women (HR, 1.33; 95% CI: 1.03, 1.73). Each 0.16-mm/(kg/m2) larger BMI-indexed DA diameter was associated with a 38% higher risk of stroke (HR, 1.38; 95% CI: 1.07, 1.78) and with a 46% greater risk of cardiovascular mortality (HR, 1.46; 95% CI: 1.10, 1.94) in women. Larger BMI-indexed AA and DA diameters were associated with greater risk of all-cause mortality in both sexes. Conclusion Larger ascending and descending thoracic aortic diameters indexed by body mass index were associated with greater risk of adverse cardiovascular outcomes and mortality in women and men. Clinical trial registration no. NTR6831 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Williams in this issue.

Myocardial blood flow during passive heat exposure in healthy young adults

INTRODUCTION Extreme heat events, such as heatwaves, are associated with a greater risk of cardiovascular mortality. However, the pathophysiology that links extreme heat and cardiovascular mortality remains unknown. Upon exposure to a hot environment, cardiac contractility and heart rate increase thereby presumably increasing myocardial metabolism. Although greater oxygen extraction contributes, an increase in myocardial metabolism is primarily met by greater myocardial blood flow. It is therefore conceivable that the required myocardial blood flow during heat exposure exceeds the capacity for myocardial blood flow to increase in vulnerable individuals. However, the extent to which myocardial blood flow increases during heat exposure is unknown. The purpose of this study is to test the hypothesis that passive heat exposure increases myocardial blood flow. METHODS Five healthy adults (31 ± 3 years, 2 women/3 men) participated in 1 experimental visit during which myocardial blood flow was measured by positron emission computed/tomography. Measurements were performed at baseline and during passive heat stress (water-perfused suit with water at 50°C) at an increase in core (rectal) temperature of 0.5°C, 1.0°C, and 1.5°C. Heart rate and rhythm (ECG) and blood pressure (automated auscultation) were also measured. RESULTS Relative to baseline, rate pressure product was greater at an increase in rectal temperature of 0.5°C (+4165 ± 623 bpm × mmHg, p=0.01), 1.0°C (+5015 ± 519 bpm × mm Hg, p<0.01) and 1.5°C (+7516 ± 261 bpm × mm Hg, p<0.01). The increase in rate pressure product was primarily due to an increase in heart rate (p<0.01), as systolic blood pressure was not affected by heat exposure (p=0.12). Relative to baseline values, myocardial blood flow increased at an increase in rectal temperature of 0.5°C (+0.45 ± 0.09 mL/min/g, p=0.03), 1.0°C (+0.61 ± 0.06 mL/min/g, p<0.01) and 1.5°C (+1.10 ± 0.22 mL/min/g, p=0.02). Overall, myocardial blood flow increased 2.7 ± 1.0-fold relative to baseline at an increase in rectal temperature of 1.5°C. The change in myocardial blood flow during heat exposure correlated with the change in rate pressure product (r=0.78, p<0.01). CONCLUSION These results suggest that passive heat exposure increases myocardial blood flow in proportion with the increase in rate pressure product in young healthy adults.

Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI-HF trial.

AimsCeramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention.Methods and resultsIn a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure (GISSI‐HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow‐up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high‐risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P < 0.05 or less) higher levels of plasma Cer(d18:1/16:0) and Cer(d18:1/24:1), but lower levels of plasma Cer(d18:1/22:0) and Cer(d18:1/24:0) than had those who did not. All plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly higher in patients who died due to cardiovascular causes. In Cox regression analyses, all five plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly associated with a greater risk of cardiovascular mortality (with unadjusted hazard ratios ranging from 1.23 to 1.59; P < 0.001 or less). These significant associations were attenuated after adjustment for multiple established risk factors, New York Heart Association functional class, left ventricular ejection fraction, use of medications, plasma pentraxin‐3 levels, and, especially, plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels. When we applied a Bonferroni correction for multiple comparisons (using a P‐threshold 0.05/5 ceramide ratios = 0.01), none of the five plasma ratios of each ceramide with Cer(d18:1/24:0) remained statistically associated with the risk of cardiovascular mortality (with adjusted hazard ratios ranging from 1.10 to 1.23).ConclusionsHigher levels of specific plasma ceramides [especially when used in ratios with Cer(d18:1/24:0)] are associated with increased cardiovascular mortality in ambulatory patients with chronic HF. However, these associations are weakened after adjustment for established cardiovascular risk factors, medication use, and plasma NT‐proBNP concentrations.

Clinical Outcomes of Complete Left Bundle Branch Block According to Strict or Conventional Definition Criteria in Patients with Normal Left Ventricular Function.

Complete left bundle branch block (cLBBB) is associated with poor outcomes in patients with heart failure (HF) but appears to have minimal effects on cardiovascular (CV) mortality in relatively healthy adults. New criteria to define strict cLBBB have been proposed. The aim of this study was to stratify the potential risk of cLBBB according to conventional or strict criteria in patients with normal ejection fraction (EF). Patients with cLBBB from 2010 to 2013 who underwent baseline echocardiography within 1 year and had a left ventricular ejection fraction (LVEF) > 50% were enrolled. A control group of patients without intraventricular conduction abnormalities matched for age and sex was included. Primary outcomes including CV mortality, HF admission, EF reduction of 40%, and total mortality were compared. A total of 137 patients with cLBBB were included, of whom 118 had strict cLBBB. The mean age was 72 ± 15 years and 56.2% were men. With a median follow-up of 4.3 years, normal LVEF patients with cLBBB but without a history of atrial fibrillation had a significantly higher risk of CV mortality (p < 0.001), EF reduction to 40% (p < 0.001), and admission for HF (p < 0.001). A similar risk of CV events was noted for the patients with conventional and strict cLBBB. In patients with normal EF and without a history of atrial fibrillation, the presence of cLBBB led to a greater risk of CV mortality, HF admission and EF reduction to < 40%. Strict cLBBB carries a similar risk of CV events to conventional cLBBB.

Which serum uric acid levels are associated with increased cardiovascular risk in the general adult population?

Our aim was to determine the serum uric acid (SUA) levels associated with an increased risk of cardiovascular (CV) and all-cause death in the general adult population. We analyzed data obtained in two independent cross-sectional surveys performed in the Czech Republic in 2006-09 and 2015-18, involving 1% population random samples in nine districts, aged 25-64years, stratified by age and gender. Ten-year mortality data were obtained in a cohort with examination in 2006-09. Final analyses included 3542 individuals (48.2% men) examined in 2006-09, and 2304 (47.4% men) examined in 2015-18. From a cohort examined in 2006-09, 122 men and 60 women were reported dead (33% and 27% from CV disease). In men, there was no association of baseline SUA levels with baseline SCORE category or 10-yearmortality rates. In women, each 10µmol/L increase in baseline SUA levels was associated with an increase in baseline SCORE category (P<.001). Receiver operating characteristic curve analyses in women identified the baseline SUA cutoff values discriminating: 1. between low/intermediate and high/very high SCORE categories (309µmol/L), 2. CV mortality (325µmol/L), and 3. all-cause mortality (298µmol/L). After adjusting for confounders including SCORE, Cox regression analysis confirmed that the baseline SUA cutoffs of 309µmol/L and 325µmol/L were associated with 4-times (P=.010) and 6-times (P=.036) greater risk of CV mortality, whereas the cutoff of 298µmol/L was associated with 87% greater risk of all-cause mortality (P=.025). In conclusion, the SUA cutoff value of 309µmol/L identified women at high/very high SCORE category and was associated with 4-times greater risk of observed CV mortality over 10years.

Blood pressure variability and arterial stiffness parameters derived from ambulatory blood pressure monitoring.

Multiple blood pressure (BP) measurements allow an evaluation of BP variability and BP‑derived arterial stiffness indices. Periodic variations in BP are well known, from beat‑to‑beat BP readings in intra‑arterial measurement to seasonal variations in BP. Diurnal BP variation has been investigated in relation to its prognostic value. People with night‑to‑day BP ratio of 1 or higher, that is, those with a higher nocturnal than daytime BP, were older than those with normal dipping status at baseline and had a greater risk of cardiovascular mortality and morbidity. Short‑term BP variability was evaluated using an intraindividual standard deviation or average real variability without any assumption of a periodic fluctuation. The ambulatory arterial stiffness index (AASI), which is derived from ambulatory BP monitoring, is a surrogate measure of arterial stiffness. An increased short‑term BP variability and the AASI have been linked to target organ damage and poor prognosis, while short‑term BP variability added only 1% or less to the prediction of a cardiovascular event. Although strict BP control at any time of the day is essential, studies are required to clarify how much additional benefit is derived from a treatment considering BP variability or the AASI in patients with hypertension.

Cardiovascular mortality in renal cell carcinoma: A population-based study.

e16085 Background: Patients with renal cell carcinoma (RCC) often harbor risk factors for cardiovascular disease and may receive anti-VEGF agents, which are associated with cardiovascular toxicity. However, the risk for cardiovascular mortality in this patient population is currently unknown. Methods: Utilizing the SEER database, we identified patients with RCC diagnosed between 2007 (approval of sunitinib) and 2015 and selected patients aged ≥ 45 years. We calculated standardized mortality ratios (SMRs) for cardiovascular mortality (ICD-10 codes I00-I99) by comparing the number of observed deaths in the database to the number of expected deaths in age-matched groups of the US general population drawn from the CDC WONDER database. Multivariable Cox regression was used to identify risk factors for cardiovascular mortality in patients with RCC. Results: We identified 36,576 patients with RCC, of which 33,748 (92.3%) were ≥ 45 years old and among these, 1650 (4.9%) died of cardiovascular diseases. The SMR for cardiovascular mortality was 2.85 (95% CI 2.72-2.99) for all patients, 2.78 (95% CI 2.62-2.95) for males and 2.86 (95% CI 2.64-3.10) for females. Among the various age groups, the SMR was 4.75 (95% CI 3.82-5.84) for patients aged 45-54 years, 3.35 (95% CI 2.93-3.83) for patients aged 55-64 years, 2.75 (95% CI 2.49-3.04) for patients aged 65-74 years, 2.25 (95% CI 2.07-2.45) for patients aged 75-84 years, and 1.47 (95% CI 1.33-1.61) for patients aged &gt; 85 years. In multivariate analysis, advancing age (HR 1.06, 95% CI 1.06-1.07), male sex (HR 1.18, 95% CI 1.05-1.33), black race (HR 1.48, 95% CI 1.27-1.73), stage IV disease (HR 1.21, 95% CI 1.01-1.45), and performance of surgery directed to the primary tumor (HR 0.33, 95% CI 0.29-0.38) were independently associated with cardiovascular mortality. Conclusions: Patients with RCC possess an almost 3-fold greater risk for cardiovascular mortality than the general population and this risk is even more pronounced in middle-aged patients. Aggressive management of modifiable cardiovascular risk factors in this patient population is thus warranted.

Growth differentiation factor-15 and the risk of cardiovascular diseases and all-cause mortality: A meta-analysis of prospective studies.

Background and AimPrevious studies have documented that the association between growth differentiation factor‐15 (GDF‐15) the risk of patients with cardiovascular diseases (CVDs). In this meta‐analysis, our main objective is to explore the associations between GDF‐15 and the risk of CVD or all‐cause mortality.MethodsPubMed and ISI Web of Science (up to January 2018) electronic databases were browsed for eligible studies. The studies provided relevant data depicted as hazard ratio (HR) with 95% confidence interval (CI), with regard to the association between GDF‐15 levels and subsequent risk of CVDs or all‐cause mortality. A random‐effect model was applied to pool the HR and 95% CI.ResultsThirty‐one prospective studies met the eligibility criteria involving 53 706 subjects with 7020 adverse outcome events. It was concluded that GDF‐15 levels were associated with an incremental risk of CVDs or all‐cause mortality. Highest GDF‐15 category was associated with greater risk of cardiovascular mortality (HR, 2.66; 95% CI, 1.69‐3.63), all‐cause mortality (HR, 2.52; 95% CI, 2.06‐2.97), and complex adverse outcome (HR, 1.81; 95% CI, 1.42‐2.21). As each log‐unit increment in GDF‐15 concentration, the corresponding risk of adverse events also escalated, cardiovascular mortality (HR, 2.11; 95% CI, 1.57‐2.66), all‐cause mortality (HR, 2.70; 95% CI, 2.29‐3.12), and complex adverse outcome (HR, 1.96; 95% CI, 1.64‐2.29).ConclusionsJudging from the results of the data analysis, GDF‐15 levels may increase the risk of CVDs or all‐cause mortality.

Subtypes of COPD Have Unique Distributions and Differential Risk of Mortality.

Previous attempts to explore the heterogeneity of chronic obstructive pulmonary disease (COPD) clustered individual patients using clinical, demographic, and disease features. We developed continuous multidimensional disease axes based on radiographic and spirometric variables that split into an airway-predominant axis and an emphysema-predominant axis. The COPD Genetic Epidemiology study (COPDGene®) is a cohort of current and former smokers, > 45 years, with at least 10 pack years of smoking history. Spirometry measures, blood pressure and body mass were directly measured. Mortality was assessed through continuing longitudinal follow-up and cause of death was adjudicated. Among 8157 COPDGene® participants with complete spirometry and computed tomography (CT) measures, the top 2 deciles of the airway-predominant and emphysema-predominant axes previously identified were used to categorize individuals into 3 groups having the highest risk for mortality using Cox proportional hazard ratios. These groups were also assessed for causal mortality. Biomarkers of COPD (fibrinogen, soluble receptor for advanced glycation end products [sRAGE], C-reactive protein [CRP], clara cell secretory protein [CC16], surfactant-D [SP-D]) were compared by group. High-risk subtype classification was defined for 2638 COPDGene® participants who were in the highest 2 deciles of either the airway-predominant and/or emphysema-predominant axis (32% of the cohort). These high-risk participants fell into 3 groups: airway-predominant disease only (APD-only), emphysema-predominant disease only (EPD-only) and combined APD-EPD. There was 26% mortality for the APD-only group, 21% mortality for the EPD-only group, and 54% mortality for the combined APD-EPD group. The APD-only group (n=1007) was younger, had a lower forced expiratory volume in 1 second (FEV1) percent (%) predicted and a strong association with the preserved ratio-impaired spirometry (PRISm) quadrant. The EPD-only group (n=1006) showed a relatively higher FEV1 % predicted and included largely GOLD stage 0, 1 and 2 partipants. Individuals in each of the 3 high-risk groups were at greater risk for respiratory mortality, while those in the APD-only group were additionally at greater risk for cardiovascular mortality. Biomarker analysis demonstrated a significant association of the APD-only group with CRP, and sRAGE demonstrated greatest significance with both the EPD-only and the combined APD-EPD groups. Among current and former smokers, individuals in the highest 2 deciles for mortality risk on the airway-predominant axis and the emphysema-predominant axis have unique associations to spirometric patterns, different imaging characteristics, biomarkers and causal mortality.

Anatomic predictors for late mortality after standard endovascular aneurysm repair

ObjectiveAbdominal aortic aneurysm (AAA) management involves a decision process that takes into account anatomic characteristics, surgical risks, patients' preferences, and expected survival. Whereas larger AAA diameter has been associated with increased mortality after both standard endovascular aneurysm repair (EVAR) and open repair, it is unclear whether survival after EVAR is influenced by other anatomic characteristics. The purpose of this study was to determine the importance of baseline anatomic features on survival after EVAR. MethodsAll patients treated at a tertiary teaching center with EVAR for intact standard infrarenal AAA from 2000 to 2014 were included. The civil data registry was queried to determine survival status; causes of death were obtained from death certificates. The primary study end point was to determine the impact of baseline morphologic features on all-cause and cardiovascular mortality after EVAR. ResultsThis study included 404 EVAR patients (12.1% women; mean age, 73 years) with a median follow-up of 5.8 years (interquartile range, 3.1-7.4 years). The 5- and 10-year overall survival rates for the entire population after EVAR were 70% (95% confidence interval [CI], 66%-75%) and 43% (95% CI, 37%-50%), respectively. Only AAA diameter >70 mm (hazard ratio [HR], 1.75; 95% CI, 1.20-3.56) was identified as an independent anatomic predictor of all-cause mortality. Death due to cardiovascular causes occurred in 60 (38.5%) patients. Aneurysm-related mortality was responsible for six of the cardiovascular-related deaths. In multivariable analysis, both neck diameter ≥30 mm (HR, 2.16; 95% CI, 1.05-4.43) and AAA diameter >70 mm (HR, 2.45; 95% CI, 1.34-4.46) were identified as independent morphologic risk factors for cardiovascular mortality, whereas >25% circumferential neck thrombus (HR, 0.32; 95% CI, 0.13-0.77) was protective. ConclusionsThis study suggests that patients with AAA diameters >70 mm are at increased risk of all-cause and cardiovascular mortality. In addition, patients with infrarenal neck diameters ≥30 mm have a greater risk of cardiovascular mortality, although AAA-related deaths were not more frequent in this group of patients. Consequently, a more aggressive management of cardiovascular medical comorbidities may be warranted to improve survival after standard EVAR in these patients.

Risk tradeoffs associated with traditional food advisories for Labrador Inuit

The traditional Inuit diet includes wild birds, fish and marine mammals, which can contain high concentrations of the neurotoxicant methylmercury (MeHg). Hydroelectric development may increase MeHg concentrations in traditional foods. Consumption advisories are often used to mitigate such risks and can result in reduced intake of traditional foods. Data from a dietary survey, MeHg exposure assessment and risk analysis for individuals in three Inuit communities in Labrador, Canada (n = 1145) in 2014 indicate reducing traditional food intake is likely to exacerbate deficiencies in n-3 polyunsaturated fatty acids and vitamins B12 and B2. Traditional foods accounted for < 5% of per-capita calories but up to 70% of nutrients consumed. Although consumption advisories could lower neurodevelopmental risks associated with an increase in MeHg exposure (90th-percentile ∆IQ = − 0.12 vs. − 0.34), they may lead to greater risks of cardiovascular mortality (90th-percentile increase: + 58% to + 116% vs. + 25%) and cancer mortality (90th-percentile increase + 2% to + 4% vs. no increase). Conversely, greater consumption of locally caught salmon mostly unaffected by hydroelectric flooding would lower all these risks (90th-percentile ∆IQ = + 0.4; cardiovascular risk: − 45%; cancer risk: − 1.4%). We thus conclude that continued consumption of traditional foods is essential for Inuit health in these communities.

Association of Solid Fuel Use With Risk of Cardiovascular and All-Cause Mortality in Rural China

When combusted indoors, solid fuels generate a large amount of pollutants such as fine particulate matter. To assess the associations of solid fuel use for cooking and heating with cardiovascular and all-cause mortality. This nationwide prospective cohort study recruited participants from 5 rural areas across China between June 2004 and July 2008; mortality follow-up was until January 1, 2014. A total of 271 217 adults without a self-reported history of physician-diagnosed cardiovascular disease at baseline were included, with a random subset (n = 10 892) participating in a resurvey after a mean interval of 2.7 years. Self-reported primary cooking and heating fuels (solid: coal, wood, or charcoal; clean: gas, electricity, or central heating), switching of fuel type before baseline, and use of ventilated cookstoves. Death from cardiovascular and all causes, collected through established death registries. Among the 271 217 participants, the mean (SD) age was 51.0 (10.2) years, and 59% (n = 158 914) were women. A total of 66% (n = 179 952) of the participants reported regular cooking (at least weekly) and 60% (n = 163 882) reported winter heating, of whom 84% (n = 150 992) and 90% (n = 147 272) used solid fuels, respectively. There were 15 468 deaths, including 5519 from cardiovascular causes, documented during a mean (SD) of 7.2 (1.4) years of follow-up. Use of solid fuels for cooking was associated with greater risk of cardiovascular mortality (absolute rate difference [ARD] per 100 000 person-years, 135 [95% CI, 77-193]; hazard ratio [HR], 1.20 [95% CI, 1.02-1.41]) and all-cause mortality (ARD, 338 [95% CI, 249-427]; HR, 1.11 [95% CI, 1.03-1.20]). Use of solid fuels for heating was also associated with greater risk of cardiovascular mortality (ARD, 175 [95% CI, 118-231]; HR, 1.29 [95% CI, 1.06-1.55]) and all-cause mortality (ARD, 392 [95% CI, 297-487]; HR, 1.14 [95% CI, 1.03-1.26]). Compared with persistent solid fuel users, participants who reported having previously switched from solid to clean fuels for cooking had a lower risk of cardiovascular mortality (ARD, 138 [95% CI, 71-205]; HR, 0.83 [95% CI, 0.69-0.99]) and all-cause mortality (ARD, 407 [95% CI, 317-497]; HR, 0.87 [95% CI, 0.79-0.95]), while for heating, the ARDs were 193 (95% CI, 128-258) and 492 (95% CI, 383-601), and the HRs were 0.57 (95% CI, 0.42-0.77) and 0.67 (95% CI, 0.57-0.79), respectively. Among solid fuel users, use of ventilated cookstoves was also associated with lower risk of cardiovascular mortality (ARD, 33 [95% CI, -9 to 75]; HR, 0.89 [95% CI, 0.80-0.99]) and all-cause mortality (ARD, 87 [95% CI, 20-153]; HR, 0.91 [95% CI, 0.85-0.96]). In rural China, solid fuel use for cooking and heating was associated with higher risks of cardiovascular and all-cause mortality. These risks may be lower among those who had previously switched to clean fuels and those who used ventilation.

Association between air pollution and cardiovascular mortality in China: a systematic review and meta-analysis.

Air pollutant levels in many Chinese cities remained significantly higher than the upper limits stated in World Health Organization guidelines. In light of limited evidence in China, we conducted a meta-analysis summarizing the association between acute exposure of air pollution and cardiovascular mortality. We searched PubMed, and CNKI databases etc. for literature published in English or Chinese up to January 2017. Outcomes were pooled and compared using random-effects model. Excess risks (ERs) per 10 μg/m3 increase in PM2.5, PM10, NO2, SO2 and O3 were evaluated. Subgroup analysis was conducted according to lag patterns (lags 0, 1, 2, 0–1, 0–2 days), gender (male vs. female), temperature (cool vs. warm) and age (< 65 vs. ≥ 65). Study bias was detected using Begg’s and Egger’s test. Of 299 articles identified, 30 met inclusion criteria. Each 10 μg/m3 increase in the concentration was associated with a higher incidence of cardiovascular mortality for PM2.5 (0.68%, 95% CI: 0.39–0.97%), PM10 (0.39%, 95% CI: 0.26–0.53%), NO2 (1.12%, 95% CI: 0.76–1.48%), SO2 (0.75%, 95% CI: 0.42–1.09%), and O3 (0.62%, 95% CI: 0.33–0.92%), respectively. Air pollution conferred greater adverse impacts on cardiovascular mortality for longer duration of exposures. Strongest associations were seen for lag 0–1 day of exposure among all pollutants. Female, lower temperature, and age > 65 years were associated with greater risks of cardiovascular mortality for all pollutants. Higher concentrations of air pollutants correlated with a greater short-term increase in cardiovascular mortality. Further high-quality studies in China are urgently warranted to determine the susceptible population, which would offer reference for policy-making to minimize adverse health effects.