Heart Disease Mortality Research Articles

Association of non-high-density lipoprotein to high-density lipoprotein ratio (NHHR) with prognosis in cancer survivors: a population-based study in the United States.

Patients with cancer frequently exhibit alterations in serum lipid profiles associated with chemotherapy. It has been reported that lipid distribution in cancer correlates with tumor progression. However, the prognostic value of serum lipid biomarkers in cancer survivors remains a subject of debate. We aim to explore the relationship between non-high-density lipoprotein to high-density lipoprotein ratio (NHHR) and the prognosis of cancer survivors. In this study, we analyzed cancer survivor data from the National Health and Nutrition Examination Survey (NHANES) from 1999-2000 to 2017-2018. The study included prospective cohorts that included total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels as well as mortality data. Weighted multivariate cox regression models, competing risk models and restricted cubic spline (RCS) models were applied to investigate the association between NHHR and cancer survival. Subgroup and sensitivity analyses were performed to test the robustness of the results. This study involved 4,177 participants, representing about 19.6 million U.S. adults. After adjustment for various factors, the lower NHHR group (≤1.64) had a 31% (HR 1.31; 95% CI [1.11,1.54], p = 0.001) higher risk of death from any cause compared to the higher NHHR group. The link between NHHR and mortality remained stable across most subgroups, with notable interactions for smoking (p = 0.006) and diabetes status (p = 0.046). A J-shaped pattern was observed between NHHR and all-cause mortality, significantly among obesity-related cancer survivors (overall association test p-value = 0.0068, non-linear association test p-value = 0.0016). However, a non-significant negative correlation was observed for cancer-specific mortality (overall association test p-value = 0.48, non-linear association test p-value = 0.66). Considering the competitive risk of heart disease and cancer-specific mortality, there is no difference between the high and low NHHR groups, while the low NHHR group showed an increased risk of non-specific causes of death (p < 0.001). The results of this study suggest that NHHR is an important indicator that is strongly associated with all-cause mortality in cancer survivors, and that this relationship may be influenced by the interaction of diabetes and smoking status. This finding may provide important information for future research and patient management.

Lipoprotein, Cholesterol, Treatment Strategies, and its Impact on Cardiovascular Diseases

A main cause of death internationally, cardiovascular (CV) illness accounted for about 31.4% of fatalities worldwide in 2012. According to estimates, a 33% decline in coronary heart disease (CHD) mortality in the United States between 1980 and 2000 was caused by a decrease in total cholesterol levels. Similar declines in CHD fatalities (varying from 19% to 46%) in other wealthy nations have been linked to lower total cholesterol levels. Lipoproteins are complex particles with a central core containing cholesterol esters and triglycerides surrounded by free cholesterol, phospholipids, and apolipoproteins, which facilitate lipoprotein formation and function. However, numerous individuals do not achieve LDL-C goal values because of statin resistance or adherence to statin medication. If cholesterol targets are not achieved with statins alone, alternative medicines include ezetimibe, fibrates, and nicotinic acid. In addition, people with familial high cholesterol levels (FH). Lipoprotein may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. HDL metabolism represents a major target for the development of therapies intended to reduce the risk of atherosclerotic cardiovascular disease. Individual cardiovascular preventative treatments should be targeted largely at individuals at higher risk who will benefit most, with the prevention and treatment of dyslipidemia being viewed as a crucial component of those interventions. Since statins have been demonstrated to lessen the risk of serious vascular events by lowering low-density lipoprotein cholesterol (LDL-C), they continue to be the first-choice medication.

Vitamin Supplementation in Cardiovascular Disease Prevention: A Systematic Review

Background: Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide, contributing to a significant public health burden. While pharmaceutical interventions like statins are effective, the increasing interest in non-pharmaceutical approaches has sparked debates on the role of vitamin supplementation in CVD prevention. Despite some studies suggesting benefits from vitamins with antioxidant properties, evidence remains inconclusive. This review aimed to evaluate the efficacy of various vitamins in reducing CVD risk using a network meta-analysis. Methods: A systematic review and network meta-analysis were conducted on clinical trials investigating vitamin supplementation for CVD prevention. Data were sourced from MEDLINE, Embase, Cochrane, and other databases. Studies were selected based on specific criteria, including randomized controlled trials with at least six months of follow-up and reported CVD outcomes. The primary outcomes included CVD mortality and risk of heart disease, while secondary outcomes focused on stroke and myocardial infarction. A random-effects model was employed to calculate risk ratios (RR), and meta-regression analyses explored the relationship between vitamin use and lipid levels. Discussion: The analysis revealed that vitamins B, D, and E were particularly effective in reducing CVD risk. However, there was no significant added benefit from combining multiple vitamins over using individual vitamins. While niacin showed potential benefits in reducing stroke and coronary artery disease in statin-intolerant populations, its overall impact on CVD mortality was not significant. Conclusion: This review provides valuable insights into the role of vitamins in CVD prevention, demonstrating that individual vitamins like B, D, and E are effective in reducing risk, while multivitamin combinations offer no additional advantage. The lack of correlation between HDL-C changes and CVD outcomes suggests that future research should focus on other mechanisms beyond lipid management.

Abstract P123: Gender Difference in the In-hospital Mortality for Hypertensive Heart Disease – United States Population-Based Survey Analysis

Background: Females have steeper increases in blood pressure than males throughout life, thus setting the stage for gender based phenotypic and clinical differences in hypertension related pathologies. We set out to determine the in-hospital mortality for the patients primarily admitted for Hypertensive Heart Disease (HHD) in the United States. Methods: Data was extracted from the National Inpatient Sample (NIS) 2016 - 2020 Database. We used ICD-10 code I11.9 to identify the patients primarily admitted for HHD. Multivariable Logistic regression was used to estimate Odds Ratio (OR) for in-hospital mortality between the two genders. Multivariable Poisson regression model was performed for yearly trends with year as the independent variable and in-hospital mortality as the dependent variable. In-hospital mortality rate trends between the two genders were compared using a group-year interaction term in a multivariable regression analysis with in-hospital mortality event as the dependent variable. All the outcomes were adjusted for age, insurance status, race, Charlson comorbidity index (CCI) and the hospital characteristics (location, bed-size). The analysis was performed on STATA 16 software. Results: We identified 1,877,150 patients with HHD. Mean age of the patient cohort was 70 years, mean CCI was 2.7 and 51% were females. Unadjusted in-hospital mortality rate for males was 1.6% compared to 1.8% for females. When adjusted for cofounders, females had lower risk of in-hospital mortality compared to males (OR: 0.95, 95% CI 0.90 – 0.99). In-hospital mortality rate for either gender did not appreciably change from 2016 – 2020, however, when compared to males the mortality rate for females rose more sharply (Interaction p = 0.038) as shown in Figure 1. Conclusion: In our adjusted population-based survey analysis, short term mortality risk for HHD was lower for females than males, however, during the study period 2016 – 2020 mortality rate for females rose more sharply than for male subjects.

Sex Disparities in Ischemic Heart Disease Mortality in Europe

BackgroundIschemic heart disease (IHD) is the leading cause of death in the European Union (EU). Understanding variations by sex, income, and countries can help in tailoring effective public health policies. ObjectivesThe purpose of the study was to examine trends in sex differences in IHD prevalence and prognosis within the EU. MethodsWe conducted a cross-sectional analysis of IHD using the Global Burden of Disease Study Database to examine trends in sex-specific age-standardized mortality rate (ASMR)-to-age-standardized prevalence rate (ASPR) ratio (ASMR-to-ASPR index) per 100,000 inhabitants/year across the EU from 2005 to 2019. ResultsMen showed higher ASMR than women. However, the ASMR-to-ASPR index was notably higher in women than in men indicating that women who develop IHD have a higher risk of dying from the disease compared with their male counterparts. Despite a significant decline in ASMR across EU from 2005 to 2019 both among women (from 1.752 to 1.662) and men (from 3.372 to 3.135), sex disparities in ASMR-to-ASPR index (EU average: 4.96% vs 4.34%) persisted (with a women-to-men ratio ranging from 1.05 to 1.44). No significant relationship was found between country-specific ASMR or country income status and ASMR-to-ASPR index. Examples include Romania, which displayed higher ASMR (men: 219.87, women: 143.54) compared with Germany (men: 107.22, women: 60.76), yet with smaller differences in ASMR-to-ASPR index between women and men (Romania: 6.54% vs 5.85%; ratio: 1.12, and Germany: 4.79% vs 3.80%; ratio: 1.26). ConclusionsMortality from IHD has decreased substantially among EU countries. However, the declines were accompanied by a persistently higher ASMR-to-ASPR index in women, indicating significant potential for further gains in closing the gender gap in IHD mortality.

Novel Classification of Cardiovascular Disease Subtypes Reveals Associations Between Mortality and Polyunsaturated Fatty Acids: Insights from the United Kingdom Biobank Study

BackgroundTraditional association studies of cardiovascular disease (CVD) categorizations and polyunsaturated fatty acids (PUFAs) yielded conflicting findings. We propose a novel classification system based on fundamental characteristics of cardiovascular patients, such as age, body mass index, waist–hip ratio, to more accurately assess the impact of PUFAs (plasma measures) such as omega (ω)-3 (n–3) and ω-6 on mortality in cardiovascular patients. MethodsPrincipal component analysis and k-means clustering were used to determine the CVD subtype. Variables included age, body mass index, waist–hip ratio, diastolic blood pressure, systolic blood pressure, total cholesterol, total triglycerides, high-density lipoprotein-cholesterol, apolipoprotein B:apolipoprotein A1, glycated hemoglobin, creatinine, albumin, C-reactive protein, white blood cell count, platelet count, and hemoglobin concentration. The association of PUFAs with all-cause, cardiovascular, and ischemic heart disease (IHD) mortality in patients with CVD was prospectively evaluated using restricted cubic splines and Cox proportional risk models. ResultsAmong the 35,096 participants, 3,786 fatalities occurred. Three distinct CVD subtypes were identified, with cluster 3 characterized by older age, male gender, and low high-density lipoprotein-cholesterol, having the highest risk of mortality. Clusters 2 and 3 had the highest DHA and ω-6/ω-3 ratios, respectively, compared with Cluster 1. The protective effects of total PUFAs, ω-3, and DHA were mainly reflected in all-cause mortality and were more significant in clusters 2 and 3. Furthermore, the ω-6/ω-3 ratio of the highest quartile increased risk of all-cause [Q3: hazard ratio (HR): 1.14, 95% confidence interval [CI]: 1.00, 1.29; Q4: HR: 1.41, 95% CI: 1.24, 1.61], CVD (Q4: HR: 1.36, 95% CI: 1.07, 1.75), and IHD mortality (Q4: HR: 1.17, 95% CI: 1.12, 2.03) in cluster 3 compared with the first quartile. ConclusionsOur findings highlight the heterogeneity of associations observed for the same type of PUFAs across distinct clusters. This association may be elucidated by the intricate interplay of various factors, encompassing inflammation, lipid metabolism, and cardiovascular health.

Cardiovascular Disease Patterns, Mortality, and Hospitalization Trends in Adults Over 18: Insights From the Behavioral Risk Factor Surveillance System Database.

Background Cardiovascular diseases (CVDs), including coronary artery disease, heart attacks, strokes, and hypertension, are the leading cause of global morbidity and mortality. Despite advancements in diagnostic techniques, treatment protocols, and public health initiatives, the prevalence of CVD continues to rise. Hence, understanding trends of predisposing factors for CVD and current treatment modalities such as medication use and frequency of hospitalization is essential for developing effective interventions and improving public health strategies. This study leverages Behavioral Risk Factor Surveillance System (BRFSS) data to analyze these trends among adults older than 18 years. Methods Data were sourced from the BRFSSdatabase, analyzing CVD patterns from 2019 to 2021. The study included adults with high cholesterol or blood pressure, coronary heart disease, stroke, and heart failure. Data analysis utilized age-adjusted prevalence, mortality, and hospitalization rates. Results The analysis of the BRFSS data revealed several key trends in CVD patterns from 2019 to 2021. There was a statistically significant increase (p<0.05) in the age-adjusted prevalence of adults taking medication for high cholesterol, rising from 28.9% to 31%, and for controlling high blood pressure, increasing from 57.7% to 60.4%. From 2019 to 2021, coronary heart disease mortality increased from 360,900 to 382,820, while stroke deaths rose from 150,005 to 162,890. Trends show rising mortality for both conditions despite missing data for some years. Mortality rates for coronary heart disease and stroke also rose and were statistically significant (p<0.05), with coronary heart disease mortality increasing from 88 to 92.8 cases per 100,000, and stroke mortality from 37 to 41.1 cases per 100,000.Hospitalization rates for heart failure among Medicare beneficiaries aged 65 and older initially decreased in 2020, likely due to the COVID-19 pandemic impacting hospital admissions, but rose again in 2021 as healthcare-seeking behaviors normalized.Significant gender and racial disparities were observed, with higher mortality rates among males (127.4 per 100,000) and Black, non-Hispanic individuals (110.5 per 100,000). Conclusions This study highlights the increasing medication use for cholesterol and blood pressure among adults older than 18 years, yet mortality rates for coronary heart disease and stroke persist. Significant gender and racial disparities in medication use and mortality rates were observed. These findings underscore the need for targeted public health intervention towards improving medication adherence and addressing social determinants of health, to reduce CVD burden and enhance health equity across diverse populations.

Space Alpha Particle Fluxes Towards the Earth Increase Human Mortality. Is It Possible an Intervention of Non-Human Intelligence?

In the present work, a dangerous phenomenon for mankind is described, increasing mortality, mainly from the most deadly diseases on the planet – circulatory diseases, in particular ischemic heart diseases. In the joint analysis of data from satellites in orbit around the Earth and from the health statistics sources EUROSTAT and US medical statistics, it became clear that, by some mechanism, flows of positively charged particles with high energy entering the Earth's orbit increase human mortality, mainly from diseases of the circulatory system, but also from diseases of many other organs and systems of the human body. The circulatory disease mortality increase as a result of said alpha radiation is by an average of 5% to 15% in a zone of maximum risk in the Northern Hemisphere, parallel to the equator and bounded by the parallels of 30° and 50° north latitude. A hypothetical mechanism based on observational evidence has been proposed, according to which this dangerous phenomenon is due to solar alpha particles of high energy sufficient to overcome the resistance of the atmosphere and reach the Earth's surface in a limited area of maximum death impact. The impact is most often short-lasting – for minutes, hours, or sometimes a few days. In the area with maximum risk, alpha particles have a detrimental effect on the human body. The area with maximum risk is limited in area and in time by two conditions 1. the path of the particles through the atmosphere to the Earth's surface is as short as possible (during the local culmination of the Sun, local noon) and 2. the direction of the incoming alpha particles coincides with the direction of the vector of geomagnetic induction at the point of maximum risk, where alpha particles are not affected by the deflecting force of the geomagnetic field. Such a coincidence between the culmination of the Sun, which changes during the year, and the direction of the geomagnetic induction vector, which is unchanged for a given point of observation, occurs twice a year for points with a geographical latitude of 30° – 50° N. Examples are given confirming the proposed mechanism of action. In the second part of the study, attention is paid to the nature of alpha particle streams reaching the Earth's orbit. In addition to those emitted by the Sun as a result of natural processes, there are also series of pulses lasting less than 5 minutes, with strict periodicity in the series day or week, with the same moment of registration of the pulses and coincidence of the pulses in the series by magnitude over extended time intervals, sometimes over the lifetime of the series from months to years. The alpha particles from each pulse in the series bombard the Earth's surface always in the same place. There are many such series, differing in time of recording and period, each of which is focused on a certain region of the Earth's surface. Such are, in particular, the series of pulses affecting the territory of the USA, Europe, and Central Asia. There is statistical confirmation in the US health statistics that the series of pulses affecting the country cause an increase in the mortality of ischemic heart disease by up to 5%. The lack of free access to detailed statistics on the cases of death in the other countries affected by the phenomenon does not allow a conclusion of the impact of the series of pulses of alpha particles on the health of their inhabitants. The strange characteristics of the mentioned series of pulses of alpha particles do not exclude the hypothesis that they are artificially generated from a non-human mind. The level of technological development of human civilization does not imply the possibility for it to generate such large-scale processes as the series of pulses of alpha particles, i.e. the highly developed non-human mind that generates them has nothing to do with human civilization. The series of pulses may be navigational signals causing unwitting casualties to humanity, but they may also be a form of murderous contact with a higher civilization that we have long sought, expecting only benefits after its realization, not suspecting that we live in this nightmarish contact indefinitely.

Disproportionately higher cardiovascular disease risk and incidence with high fructose corn syrup sweetened beverage intake among black young adults–the CARDIA study

BackgroundThe black/white heart disease mortality disparity began increasing in the early 1980’s, coincident with the switch from sucrose to high-fructose-corn-syrup/(HFCS) in the US food supply. There has been more fructose in HFCS than generally-recognized-as-safe/GRAS, which has contributed to unprecedented excess-free-fructose/(unpaired-fructose) in foods/beverages. Average- per-capita excess-free-fructose, from HFCS, began exceeding dosages/(5-10 g) that trigger fructose-malabsorption in the early 1980’s. Fructose malabsorption contributes to gut-dysbiosis and gut-in-situ-fructosylation of dietary peptides/incretins/(GLP-1/GIP) which forms atherosclerotic advanced-glycation-end-products. Both dysregulate gut endocrine function and are risk factors for cardiovascular disease/(CVD). Limited research shows that African Americans have higher fructose malabsorption prevalence than others. CVD risk begins early in life.MethodsCoronary-Artery-Risk-Development-in-Adults/(CARDIA) study data beginning in 1985–86 with 2186 Black and 2277 White participants, aged 18–30 y, were used to test the hypothesis that HFCS sweetened beverage intake increases CVD risk/incidence, more among Black than White young adults, and at lower intakes; while orange juice-a low excess-free-fructose juice with comparable total sugars and total fructose, but a 1:1 fructose-to-glucose-ratio, i.e., low excess-free-fructose, does not. Cox proportional hazards models were used to calculate hazard ratios.ResultsHFCS sweetened beverage intake was associated with higher CVD risk (HR = 1.7) than smoking (HR = 1.6). CVD risk was higher at lower HFCS sweetened beverage intake among Black than White participants. Intake, as low as 3 times/wk, was associated with twice the CVD risk vs. less frequent/never, among Black participants only (HR 2.1, 95% CI 1.2–3.7; P = 0.013). Probability of an ordered relationship approached significance. Among Black participants, CVD incidence jumped 62% from 59.8/1000, among ≤ 2-times/wk, to 96.9/1000 among 3–6 times/wk consumers. Among White participants, CVD incidence increased from 37.6/1000, among ≤ 1.5-times/wk, to 41.1/1000, among 2 times/wk–once/d – a 9% increase. Hypertension was highest among Black daily HFCS sweetened beverage consumers.ConclusionThe ubiquitous presence of HFCS over-the-past-40 years, at higher fructose-to-glucose ratios than generally-recognized-as-safe, may have contributed to CVD racial disparities, due to higher fructose-malabsorption prevalence among Black individuals, unpaired/excess-free-fructose induced gut dysbiosis and gut fructosylation of dietary peptides/incretins (GLP-1/GIP). These disturbances contribute to atherosclerotic plaque; promote incretin insufficiency/dysregulation/altered satiety/dysglycemia; decrease protective microbiota metabolites; and increase hypertension, CVD morbidity and mortality.

An ensemble machine learning model for predicting one-year mortality in elderly coronary heart disease patients with anemia

ObjectiveThis study was designed to develop and validate a robust predictive model for one-year mortality in elderly coronary heart disease (CHD) patients with anemia using machine learning methods.MethodsDemographics, tests, comorbidities, and drugs were collected for a cohort of 974 elderly patients with CHD. A prospective analysis was performed to evaluate predictive performances of the developed models. External validation of models was performed in a series of 112 elderly CHD patients with anemia.ResultsThe overall one-year mortality was 43.6%. Risk factors included heart rate, chronic heart failure, tachycardia and β receptor blockers. Protective factors included hemoglobin, albumin, high density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR), left ventricular ejection fraction (LVEF), aspirin, clopidogrel, calcium channel blockers, angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and statins. Compared with other algorithms, an ensemble machine learning model performed the best with area under the curve (95% confidence interval) being 0.828 (0.805–0.870) and Brier score being 0.170. Calibration and density curves further confirmed favorable predicted probability and discriminative ability of an ensemble machine learning model. External validation of Ensemble Model also exhibited good performance with area under the curve (95% confidence interval) being 0.825 (0.734–0.916) and Brier score being 0.185. Patients in the high-risk group had more than six-fold probability of one-year mortality compared with those in the low-risk group (P < 0.001). Shaley Additive exPlanation identified the top five risk factors that associated with one-year mortality were hemoglobin, albumin, eGFR, LVEF, and ACEIs/ARBs.ConclusionsThis model identifies key risk factors and protective factors, providing valuable insights for improving risk assessment, informing clinical decision-making and performing targeted interventions. It outperforms other algorithms with predictive performance and provides significant opportunities for personalized risk mitigation strategies, with clinical implications for improving patient care.

Sitting Time and Its Interaction With Physical Activity in Relation to All-Cause and Heart Disease Mortality in U.S. Adults With Diabetes.

To evaluate whether associations between sitting time and all-cause and heart disease mortality are modified by physical activity in adults with diabetes. Data came from 6,335 U.S. adults with diabetes from National Health and Nutrition Examination Survey 2007-2018 (baseline), with mortality follow-up through 2019. Sitting time and moderate to vigorous physical activity (MVPA) were self-reported. Cox models were adjusted for sociodemographics, lifestyle factors, and medical conditions. Over a median follow-up of 5.9 years, 1,278 all-cause and 354 heart disease deaths were documented (mean age, 59.6 years; 48.3% female). Longer sitting time was associated with greater all-cause and heart disease mortality risk in inactive (MVPA <10 min/week) or insufficiently active (MVPA 10 to <150 min/week) adults with diabetes, but not in active adults (MVPA ≥150 min/week) (all-cause mortality: P = 0.003 for interaction; heart disease mortality: P = 0.008 for interaction). In adults with diabetes, meeting guideline-recommended physical activity may offset the elevated all-cause and heart disease mortality risk associated with excessive sitting time.

Impact of non-alcoholic fatty liver disease and fibrosis on mortality and kidney outcomes in patients with type 2 diabetes and chronic kidney disease: A multi-cohort longitudinal study.

To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events. In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events. In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.

CXCL9, IL2RB, and SPP1, potential diagnostic biomarkers in the co-morbidity pattern of atherosclerosis and non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is a hepatocyte inflammation based on hepatocellular steatosis, yet there is no effective drug treatment. Atherosclerosis (AS) is caused by lipid deposition in the endothelium, which can lead to various cardiovascular diseases. NASH and AS share common risk factors, and NASH can also elevate the risk of AS, causing a higher morbidity and mortality rate for atherosclerotic heart disease. Therefore, timely detection and diagnosis of NASH and AS are particularly important. In this study, differential gene expression analysis and weighted gene co-expression network analysis were performed on the AS (GSE100927) and NASH (GSE89632) datasets to obtain common crosstalk genes, respectively. Then, candidate Hub genes were screened using four topological algorithms and externally validated in the GSE43292 and GSE63067 datasets to obtain Hub genes. Furthermore, immune infiltration analysis and gene set variation analysis were performed on the Hub genes to explore the underlying mechanisms. The DGIbd database was used to screen candidate drugs for AS and NASH. Finally, a NASH model was constructed using free fatty acid-induced human L02 cells, an AS model was constructed using lipopolysaccharide-induced HUVECs, and a co-morbidity model was constructed using L02 cells and HUVECs to verify Hub gene expression. The result showed that a total of 113 genes common to both AS and NASH were identified as crosstalk genes, and enrichment analysis indicated that these genes were mainly involved in the regulation of immune and metabolism-related pathways. 28 candidate Hub genes were screened according to four topological algorithms, and CXCL9, IL2RB, and SPP1 were identified as Hub genes after in vitro experiments and external dataset validation. The ROC curves and SVM modeling demonstrated the good diagnostic efficacy of these three Hub genes. In addition, the Hub genes are strongly associated with immune cell infiltration, especially macrophages and γ–δ T cell infiltration. Finally, five potential therapeutic drugs were identified. has-miR-185 and hsa-miR-335 were closely related to AS and NASH. This study demonstrates that CXCL9, IL2RB, and SPP1 may serve as potential biomarkers for the diagnosis of the co-morbidity patterns of AS and NASH and as potential targets for drug therapy.

Association of oral health with all-cause and cause-specific mortality in older Chinese adults: A 14-year follow-up of the Guangzhou Biobank Cohort study.

Poor oral hygiene is associated with overall wellness, but evidence regarding associations of oral health with all-cause mortality remain inconclusive. We aimed to examine the associations of oral health with all-cause and cause-specific mortality in middle-aged and older Chinese adults. 28 006 participants were recruited from 2003-2008 and followed up until 2021. Oral health was assessed by face-to-face interview and causes of death was identified via record linkage. Cox regression yielded hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment of multiple potential confounders. During an average of 14.3 years of follow-up, we found that a lower frequency of toothbrushing was associated with higher risks of all-cause mortality with a dose-response pattern (P for trend <0.001). Specially, the adjusted HR (95% CI) (vs. ≥ twice/d) was 1.16 (1.10, 1.22) (P < 0.001) for brushing once/d and 1.27 (1.00, 1.61) (P = 0.048) for < once/d. Similar associations were also found for cardiovascular disease (CVD), stroke, and respiratory disease mortality, but not for ischemic heart disease (IHD) and cancer mortality. A greater number of missing teeth was also associated with higher risks of all-cause, CVD, stroke, and respiratory disease mortality with a dose-response pattern (all P for trend <0.05). The association of missing teeth with all-cause mortality was stronger in lower-educated participants. Both less frequent toothbrushing and a greater number of missing teeth were associated with higher risks of all-cause, CVD, stroke, and respiratory disease mortality, showing dose-response patterns, but not with IHD and cancer mortality. Moreover, the dose-response association of missing teeth with all-cause mortality was stronger in lower-educated participants.

Effect of Meal-Timing on the Association of Unsaturated Fatty Acids with All-Cause and Cardiovascular Mortality among Adults: A Prospective Cohort Study with 10-Year Follow-Up.

Conflicting results have been reported on the association of dietary unsaturated fatty acids (UFAs) with longevity and cardiovascular health. Most previous studies have focused only on the amount of UFAs consumed, not the timing of intake. This prospective cohort study used data from 30,136 adults aged 18 years and older. Intakes of UFAs by meal time and types were assessed by a 24-h dietary recall for two days. The covariate-adjusted survey-weighted Cox proportional hazards models were performed to evaluate the associations of dietary total unsaturated fatty acid (TUFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) intakes throughout the day and three meals with mortality. During a median of 10.0 years of follow-up, 4510 total deaths occurred. All-cause mortality decreased with increasing intakes at dinner of TUFA (HR: 0.87 [0.77-0.98]), PUFA (HR: 0.81 [0.73-0.91]), and MUFA (HR: 0.88 [0.77-0.99]). With an increased intake of PUFA at dinner, CVD mortality showed a decreasing trend. However, the inverted L-shaped non-linear trend in all-cause mortality was found with increasing intake at breakfast of TUFA (HR: 1.35 [1.17-1.57], Q3 vs. Q1), PUFA (HR: 1.30 [1.13-1.50]), and MUFA (HR: 1.28 [1.13-1.45]). Meanwhile, increased breakfast intake of UFAs was associated with increased CVD and heart disease mortality. Meal timing influences the association of UFAs with all-cause and CVD-related mortality.

Interventions for primary prevention of cardiovascular disease: umbrella review of systematic reviews.

Cardiovascular diseases are the leading cause of death globally. The aim of this overview of systematic reviews was to compare the effectiveness of different pharmacological and non-pharmacological interventions for the primary prevention of cardiovascular disease. A structured search of the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and the Database of Abstracts of Reviews of Effects archive was conducted to find systematic reviews that reported the effect of various pharmacological and non-pharmacological interventions for the primary prevention of cardiovascular disease from inception to March 2021. References of included studies were also checked. The included systematic reviews' methodological quality was assessed using the Assessment of Multiple Systematic Reviews 2 instrument (range, 0-16). The outcomes of each included review's meta-analysis were extracted and described narratively. This study analysed 95 systematic reviews, including 41 on non-pharmacological interventions and 54 on pharmacological interventions for cardiovascular health. The majority of the reviews focused on lipid-lowering interventions (n = 25) and antiplatelet medications (n = 21), followed by nutritional supplements, dietary interventions, physical activity, health promotion and other interventions. Only 1 of the 10 reviews addressing cardiovascular mortality showed a potential benefit, while the others found no effect. Antiplatelets were found to have a beneficial effect on all-cause mortality in 2 out of 12 meta-analyses and on major cardiovascular disease events in 8 out of 17 reviews. Lipid-lowering interventions showed beneficial effects on cardiovascular disease mortality, all-cause mortality and major cardiovascular disease events in varying numbers of the reviews. Glucose-lowering medications demonstrated significant benefits for major cardiovascular events, coronary heart disease events and mortality. However, the combination of dietary interventions, physical activities, nutritional supplements and polypills showed little or no significant benefit for major cardiovascular outcomes or mortality. More research is needed to determine whether the effect of treatment varies depending on population characteristics. The findings of this review should be interpreted with caution because the majority of studies of non-pharmacological interventions compare primary prevention with usual care, which may include recommended pharmacological treatment in higher-risk patients (e.g. statins and/or antihypertensive medications, etc.). In addition, randomised controlled trial evidence may be better suited to the study of pharmacological interventions than dietary and lifestyle interventions. This umbrella review captured the variability in different interventions on randomised controlled trial evidence on interventions for primary prevention of cardiovascular disease and identified areas that may benefit from further research. Specifically, this review focused on randomised controlled trial evidence on interventions for primary prevention of cardiovascular disease. Researchers may use these findings as a resource to direct new intervention studies and network meta-analyses to compare the efficacy of various interventions based on these findings. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme as award number 17/148/05.

Aortic stiffness: an age-related prognostic marker?

Aortic stiffness, a consequence of vascular aging, is an independent predictor of cardiovascular morbidity and mortality. However, the impact of age and sex on its predictive performance remains unclear. We have included 6046 individuals from the population-based Rotterdam study. Survival analyses were performed to investigate the impact of age and sex on the link between aortic stiffness and outcomes, including coronary heart disease (CHD), stroke, cardiovascular disease (CVD), cardiovascular and all-cause mortality. The added predictive value of aortic stiffness across age categories and by sex was assessed by using explained variation, Harrell's C index and Integrated Discrimination Improvement (IDI). Aortic stiffness was independently associated with all outcomes [hazard ratio (95% confidence interval; CI): 1.16 (1.04-1.22) for CHD, 1.09 (1.00-1.19) for stroke, 1.11 (1.05-1.18) for CVD, 1.14 (1.05-1.23) for cardiovascular mortality, 1.08 (1.03-1.13) for all-cause mortality]. The strength of the association between aortic stiffness and stroke, cardiovascular and all-cause mortality decreased significantly by advancing age. The variance of the outcome (R2) explained by aortic stiffness alone was noticeable in individuals younger than 60 years and negligible in the other age categories. The association of aortic stiffness and CHD was stronger in women than in men. Similarly, the difference in R2 between women and men was greater for CHD than for the other considered outcomes. Our findings suggest that the gain in explained variation caused by aortic stiffness for CVD and mortality might be limited to individuals younger than 60 years.

Volatile organic compounds and mortality from ischemic heart disease: A case-cohort study

BackgroundVolatile organic compounds (VOCs) are major components of air pollution and tobacco smoke, two known risk factors for cardiovascular diseases. VOCs are ubiquitous in the environment and originate from a wide range of sources, including the burning of biomass, fossil fuels, and consumer products. Direct evidence for associations between specific VOCs and ischemic heart disease (IHD) mortality in the general population is scarce. MethodsIn a case-cohort study (stratified by age groups, sex, residence, and tobacco smoking), nested within the population-based Golestan cohort study (n = 50,045, 40–75 years, 58% women, enrollment: 2004–2008) in northeastern Iran, we measured urinary concentrations of 20 smoking-related VOC biomarkers using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. We calculated hazard ratio (HR) and 95% confidence interval (CI) for their associations with IHD mortality during follow-up to 2018, using Cox regression models adjusted for age, ethnicity, education, marital status, body mass index, physical activity, wealth, and urinary cotinine. ResultsThere were 575 non-cases from random subcohort and 601 participants who died from IHD, mean (standard deviation) age, 58.2 (9.3) years, with a median of 8.4 years follow-up. Significant associations [3rd vs. 1st tertile, HR (95% CI), P for trend] were observed between biomarkers of acrylamide [1.68(1.05,2.69), 0.025], acrylonitrile [2.06(1.14,3.72), 0.058], acrolein [1.98(1.30,3.01), 0.003 and 2.44(1.43,4.18), 0.002], styrene/ethylbenzene [1.83(1.19,2.84), 0.007 and 1.44(1.01,2.07), 0.046], dimethylformamide/methylisocyanate [2.15(1.33,3.50), 0.001], and 1,3butadiene [2.35(1.52,3.63),<0.001] and IHD mortality. These associations were independent of tobacco smoking, and they were only present in the non-smoking subgroup. ConclusionOur findings provide direct evidence for associations between exposure to several VOCs with widespread household and commercial use and IHD mortality many years after these exposures. These results highlight the importance of VOC exposure in the general population as a risk factor for cardiovascular diseases and underline the importance of bio-monitoring non-tobacco VOC exposure.

An application of the Bayesian network model based on the EN-ESL-GA algorithm: Exploring the predictors of heart disease in middle-aged and elderly people in China.

The morbidity and mortality of heart disease are increasing in middle-aged and elderly people in China. It is necessary to explore relationships and interactive associations between heart disease and its risk factors in order to prevent heart disease. To establish a Bayesian network model of heart disease and its influencing factors in middle-aged and elderly people in China, and explore the applicability of the elite-based structure learner using genetic algorithm based on ensemble learning (EN-ESL-GA) algorithm in etiology analysis and disease prediction. Based on the 2013 national tracking survey data from China Health and Retirement Longitudinal Study (CHARLS) database, EN-ESL-GA algorithm was used to learn the Bayesian network structure. Then we input the data and the learned network structure into the Netica software for parameter learning and inference analysis. The Bayesian network model based on the EN-ESL-GAalgorithm can effectively excavate the complex network relationships and interactive associations between heart disease and its risk factors in middle-aged and elderly people in China. The Bayesian network model based on the EN-ESL-GA algorithm has good applicability and application prospect in the prediction of diseases prevalence risk.

Long-term exposure to wildland fire smoke PM2.5 and mortality in the contiguous United States.

Despite the substantial evidence on the health effects of short-term exposure to ambient fine particles (PM2.5), including increasing studies focusing on those from wildland fire smoke, the impacts of long-term wildland fire smoke PM2.5 exposure remain unclear. We investigated the association between long-term exposure to wildland fire smoke PM2.5 and non-accidental mortality and mortality from a wide range of specific causes in all 3,108 counties in the contiguous U.S., 2007-2020. Controlling for non-smoke PM2.5, air temperature, and unmeasured spatial and temporal confounders, we found a non-linear association between 12-month moving average concentration of smoke PM2.5 and monthly non-accidental mortality rate. Relative to a month with the long-term smoke PM2.5 exposure below 0.1 μg/m3, non-accidental mortality increased by 0.16-0.63 and 2.11 deaths per 100,000 people per month when the 12-month moving average of PM2.5 concentration was of 0.1-5 and 5+ μg/m3, respectively. Cardiovascular, ischemic heart disease, digestive, endocrine, diabetes, mental, and chronic kidney disease mortality were all found to be associated with long-term wildland fire smoke PM2.5 exposure. Smoke PM2.5 contributed to approximately 11,415 non-accidental deaths/year (95% CI: 6,754, 16,075) in the contiguous U.S. Higher smoke PM2.5-related increases in mortality rates were found for people aged 65 above. Positive interaction effects with extreme heat (monthly number of days with daily mean air temperature higher than the county's 90th percentile warm season air temperature) were also observed. Our study identified the detrimental effects of long-term exposure to wildland fire smoke PM2.5 on a wide range of mortality outcomes, underscoring the need for public health actions and communications that span the health risks of both short- and long-term exposure.