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Annals of Internal Medicine Sep 2023Cardiovascular disease (CVD) mortality is persistently higher in the Black population than in other racial and ethnic groups in the United States. (Observational Study)
Observational Study
BACKGROUND
Cardiovascular disease (CVD) mortality is persistently higher in the Black population than in other racial and ethnic groups in the United States.
OBJECTIVE
To examine the degree to which social, behavioral, and metabolic risk factors are associated with CVD mortality and the extent to which racial differences in CVD mortality persist after these factors are accounted for.
DESIGN
Prospective cohort study.
SETTING
NHANES (National Health and Nutrition Examination Survey) 1999 to 2018.
PARTICIPANTS
A nationally representative sample of 50 808 persons aged 20 years or older.
MEASUREMENTS
Data on social, behavioral, and metabolic factors were collected in each NHANES survey using standard methods. Deaths from CVD were ascertained from linkage to the National Death Index with follow-up through 2019.
RESULTS
Over an average of 9.4 years of follow-up, 2589 CVD deaths were confirmed. The age- and sex-standardized rates of CVD mortality were 484.7 deaths per 100 000 person-years in Black participants, 384.5 deaths per 100 000 person-years in White participants, 292.4 deaths per 100 000 person-years in Hispanic participants, and 255.1 deaths per 100 000 person-years in other race groups. In a multiple Cox regression analysis adjusted for all measured risk factors simultaneously, several social (unemployment, low family income, food insecurity, lack of home ownership, and unpartnered status), behavioral (current smoking, lack of leisure-time physical activity, and sleep <6 or >8 h/d), and metabolic (obesity, hypertension, and diabetes) risk factors were associated with a significantly higher risk for CVD death. After adjustment for these metabolic, behavioral, and social risk factors separately, hazard ratios of CVD mortality for Black compared with White participants were attenuated from 1.54 (95% CI, 1.34 to 1.77) to 1.34 (CI, 1.16 to 1.55), 1.31 (CI, 1.15 to 1.50), and 1.04 (CI, 0.90 to 1.21), respectively.
LIMITATION
Causal contributions of social, behavioral, and metabolic risk factors to racial and ethnic disparities in CVD mortality could not be established.
CONCLUSION
The Black-White difference in CVD mortality diminished after adjustment for behavioral and metabolic risk factors and completely dissipated with adjustment for social determinants of health in the U.S. population.
PRIMARY FUNDING SOURCE
National Institutes of Health.
Topics: Adult; Humans; United States; Cardiovascular Diseases; Nutrition Surveys; Prospective Studies; Risk Factors; Racial Groups
PubMed: 37579311
DOI: 10.7326/M23-0507 -
EBioMedicine May 2024The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization...
BACKGROUND
The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations.
METHODS
Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P < 5 × 10) level were selected from a genome-wide association study. Summary statistics for gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analyses were conducted for genetically determined LST with adjustment for MVPA and vice versa. We also performed multivariable MR with adjustment for genetically proxied smoking, body mass index (BMI), waist-to-hip ratio, type 2 diabetes, and fasting insulin for both exposures.
FINDINGS
Genetically proxied longer LST was associated with an increased risk of gastrointestinal reflux, gastric ulcer, duodenal ulcer, chronic gastritis, irritable bowel syndrome, diverticular disease, Crohn's disease, ulcerative colitis, non-alcoholic fatty liver disease, alcoholic liver disease, cholangitis, cholecystitis, cholelithiasis, acute pancreatitis, chronic pancreatitis, and acute appendicitis. Most associations remained after adjustment for genetic liability to MVPA. Genetic liability to MVPA was associated with decreased risk of gastroesophageal reflux, gastric ulcer, chronic gastritis, irritable bowel syndrome, cholecystitis, cholelithiasis, acute and chronic pancreatitis. The associations attenuated albeit directionally remained after adjusting for genetically predicted LST. Multivariable MR analysis found that BMI and type 2 diabetes mediated the associations of LST and MVPA with several gastrointestinal diseases.
INTERPRETATION
The study suggests that a sedentary lifestyle may play a causal role in the development of many gastrointestinal diseases.
FUNDING
Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), Natural Science Foundation of Hunan Province (2021JJ30999), Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20210351), Swedish Research Council (Vetenskapsrådet, 2019-00977), Swedish Cancer Society (Cancerfonden), the Wellcome Trust (225790/7/22/Z), United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7) and National Institute for Health Research Cambridge Biomedical Research Centre (NHIR203312).
Topics: Humans; Mendelian Randomization Analysis; Sedentary Behavior; Exercise; Gastrointestinal Diseases; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Risk Factors
PubMed: 38583262
DOI: 10.1016/j.ebiom.2024.105110 -
JAMA Network Open Mar 2024Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is a commonly used estimate of obesity, which is a complex trait affected by...
IMPORTANCE
Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is a commonly used estimate of obesity, which is a complex trait affected by genetic and lifestyle factors. Marked weight gain and loss could be associated with adverse biological processes.
OBJECTIVE
To evaluate the association between BMI variability and incident cardiovascular disease (CVD) events in 2 distinct cohorts.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from the Million Veteran Program (MVP) between 2011 and 2018 and participants in the UK Biobank (UKB) enrolled between 2006 and 2010. Participants were followed up for a median of 3.8 (5th-95th percentile, 3.5) years. Participants with baseline CVD or cancer were excluded. Data were analyzed from September 2022 and September 2023.
EXPOSURE
BMI variability was calculated by the retrospective SD and coefficient of variation (CV) using multiple clinical BMI measurements up to the baseline.
MAIN OUTCOMES AND MEASURES
The main outcome was incident composite CVD events (incident nonfatal myocardial infarction, acute ischemic stroke, and cardiovascular death), assessed using Cox proportional hazards modeling after adjustment for CVD risk factors, including age, sex, mean BMI, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, diabetes status, and statin use. Secondary analysis assessed whether associations were dependent on the polygenic score of BMI.
RESULTS
Among 92 363 US veterans in the MVP cohort (81 675 [88%] male; mean [SD] age, 56.7 [14.1] years), there were 9695 Hispanic participants, 22 488 non-Hispanic Black participants, and 60 180 non-Hispanic White participants. A total of 4811 composite CVD events were observed from 2011 to 2018. The CV of BMI was associated with 16% higher risk for composite CVD across all groups (hazard ratio [HR], 1.16; 95% CI, 1.13-1.19). These associations were unchanged among subgroups and after adjustment for the polygenic score of BMI. The UKB cohort included 65 047 individuals (mean [SD] age, 57.30 (7.77) years; 38 065 [59%] female) and had 6934 composite CVD events. Each 1-SD increase in BMI variability in the UKB cohort was associated with 8% increased risk of cardiovascular death (HR, 1.08; 95% CI, 1.04-1.11).
CONCLUSIONS AND RELEVANCE
This cohort study found that among US veterans, higher BMI variability was a significant risk marker associated with adverse cardiovascular events independent of mean BMI across major racial and ethnic groups. Results were consistent in the UKB for the cardiovascular death end point. Further studies should investigate the phenotype of high BMI variability.
Topics: Female; Male; Humans; Middle Aged; Body Mass Index; Ischemic Stroke; Cohort Studies; Retrospective Studies; Myocardial Infarction; Cholesterol, HDL
PubMed: 38512255
DOI: 10.1001/jamanetworkopen.2024.3062 -
Methodist DeBakey Cardiovascular Journal 2024Pulmonary embolus (PE) carries a significant impending morbidity and mortality, especially in intermediate and high-risk patients, and the choice of initial... (Review)
Review
Pulmonary embolus (PE) carries a significant impending morbidity and mortality, especially in intermediate and high-risk patients, and the choice of initial anticoagulation that allows for therapeutic adjustment or manipulation is important. The preferred choice of anticoagulation management includes direct oral anticoagulants. Vitamin K antagonists and low-molecular-weight heparin are preferred in special populations or selected patients such as breastfeeding mothers, those with end-stage renal disease, or obese patients, among others. This article reviews the primary and longer-term considerations for anticoagulation management in patients with PE and highlights special patient populations and risk factor considerations.
Topics: Humans; Pulmonary Embolism; Anticoagulants; Risk Factors; Treatment Outcome; Blood Coagulation; Administration, Oral; Risk Assessment; Hemorrhage; Vitamin K; Clinical Decision-Making
PubMed: 38765210
DOI: 10.14797/mdcvj.1338 -
Biomedicines Oct 2023Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals... (Review)
Review
Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals within the general population, and patients with diabetes and hypertension are particularly at risk. This disorder disrupts the physiological mechanisms of the body, including water and electrolyte balance, blood pressure regulation, the excretion of toxins, and vitamin D metabolism. Consequently, patients are exposed to risks such as hyperkalemia, hyperphosphatemia, metabolic acidosis, and blood pressure abnormalities. These risks can be reduced by implementing appropriate diagnostic methods, followed by non-pharmacological (such as physical activity, dietary, and lifestyle adjustment) and pharmacological strategies after diagnosis. Selecting the appropriate diet and suitable pharmacological treatment is imperative in maintaining kidney function as long as possible. Drugs such as finerenone, canakinumab, and pentoxifylline hold promise for improved outcomes among CKD patients. When these interventions prove insufficient, renal replacement therapy becomes essential. This is particularly critical in preserving residual renal function while awaiting renal transplantation or for patients deemed ineligible for such a procedure. The aim of this study is to present the current state of knowledge and recent advances, providing novel insights into the treatment of chronic kidney disease.
PubMed: 37893119
DOI: 10.3390/biomedicines11102746 -
EBioMedicine Jun 2024Insomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted...
BACKGROUND
Insomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted insomnia and EOC risk and survival through a two-sample Mendelian randomization (MR) study.
METHODS
Insomnia was proxied using genetic variants identified in a genome-wide association study (GWAS) meta-analysis of UK Biobank and 23andMe. Using genetic associations with EOC risk and overall survival from the Ovarian Cancer Association Consortium (OCAC) GWAS in 66,450 women (over 11,000 cases with clinical follow-up), we performed Iterative Mendelian Randomization and Pleiotropy (IMRP) analysis followed by a set of sensitivity analyses. Genetic associations with survival and response to treatment in ovarian cancer study of The Cancer Genome Atlas (TCGA) were estimated controlling for chemotherapy and clinical factors.
FINDINGS
Insomnia was associated with higher risk of endometrioid EOC (OR = 1.60, 95% CI 1.05-2.45) and lower risk of high-grade serous EOC (HGSOC) and clear cell EOC (OR = 0.79 and 0.48, 95% CI 0.63-1.00 and 0.27-0.86, respectively). In survival analysis, insomnia was associated with shorter survival of invasive EOC (OR = 1.45, 95% CI 1.13-1.87) and HGSOC (OR = 1.4, 95% CI 1.04-1.89), which was attenuated after adjustment for body mass index and reproductive age. Insomnia was associated with reduced survival in TCGA HGSOC cases who received standard chemotherapy (OR = 2.48, 95% CI 1.13-5.42), but was attenuated after adjustment for clinical factors.
INTERPRETATION
This study supports the impact of insomnia on EOC risk and survival, suggesting treatments targeting insomnia could be pivotal for prevention and improving patient survival.
FUNDING
National Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.
Topics: Humans; Female; Mendelian Randomization Analysis; Sleep Initiation and Maintenance Disorders; Ovarian Neoplasms; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Risk Factors; Carcinoma, Ovarian Epithelial; Survival Analysis
PubMed: 38823087
DOI: 10.1016/j.ebiom.2024.105175 -
Frontiers in Public Health 2023Shift work has become an increasingly common work mode globally. This study aimed to investigate the association between shift work and the risk of incident...
INTRODUCTION
Shift work has become an increasingly common work mode globally. This study aimed to investigate the association between shift work and the risk of incident gastroesophageal reflux disease (GORD), an upward gastrointestinal disorder disease worldwide, and to explore the mediating factors.
METHOD
A total of 262,722 participants from the UK Biobank free of GORD and related gastrointestinal diseases were included to investigate the association and potential mediators between shift work and incident GORD. Multivariate-adjusted Cox models were used to evaluate the association between shift work status and GORD incidence.
RESULTS
Compared to non-shift workers, shift workers had a 1.10-fold greater risk of incident GORD [95% confidence intervals (CIs): 1.03, 1.18], after adjusting for a range of potential confounders. However, the excess risk of GORD attenuated to the null after further adjusting for selected mediators. Specifically, the association was mediated by sleep patterns (25.7%), healthy behaviors (16.8%), depressive symptoms (20.2%), chronic conditions (13.3%), and biological factors (17.6%). After adjustment for all the mediators together, the association was attenuated by 71.5%.
DISCUSSION
Our findings indicated that long-term shift workers may have a higher risk of incident GORD, yet the excess risk may be explained by poor sleep quality, unhealthy behaviors, depressive symptoms, etc. This has positive implications for protecting the health of shift workers.
Topics: Humans; Shift Work Schedule; Gastroesophageal Reflux; Health Behavior; Sleep Quality
PubMed: 37693713
DOI: 10.3389/fpubh.2023.1192517 -
Biology of Sex Differences Sep 2023There is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the...
OBJECTIVES
There is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the risk of myocardial infarction (MI) in pre- and post-menopausal women, and men in the UK Biobank.
METHODS
The UK Biobank is a prospective population-based cohort study, that recruited over 500,000 (aged 40-69 years) women and men between 2006 and 2010. Sex specific cox regression models, estimating hazard ratios (HRs) and women to men ratio of HRs (RHR) with respective 95% confidence intervals (CI), were used to model the association of sex hormones [oestrogen, testosterone, oestrogen: testosterone (O/T) ratio, sex hormone-binding globulin (SHBG) and the free androgen index (FAI)], measured at study baseline, with incident MI for women and men.
RESULTS
Data were from 479,797 participants [264,282 (55.1%) women] without a history of MI at study baseline. Over 12.5 years of follow-up, there were 4,908 MI events in women and 10,517 in men. Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, a unit higher log-transformed O/T ratio was associated with a lower risk of MI 0.79 (0.65, 0.95) after adjustment for traditional CVD risk factors. The corresponding women to men RHR (95% CI) was 1.24 (0.99, 1.56). Higher SHBG (per unit) was also associated with a lower risk of MI in men 0.94 (0.89, 0.99), and not in women 1.02 (0.95, 1.09) after multiple adjustment, the corresponding women to men RHR (95% CI) was 1.09 (1.00, 1.18). Higher FAI was associated with a higher risk of MI in men 1.09 (1.02, 1.15), though not in women 0.97 (0.92, 1.02), the corresponding women to men RHR was 0.89 (0.82, 0.97). Finally, there were differential effects in the association of SHBG and FAI between pre- and post-menopausal women.
CONCLUSIONS
A higher O/T ratio was associated with a lower risk of MI, and a higher FAI with a higher risk of MI after adjustment for CVD risk factors in men, but not in women. Thus, hormone ratios, rather than each alone, may play an important role in modulating the effect of MI.
Topics: Male; Female; Humans; Prospective Studies; Biological Specimen Banks; Cohort Studies; Gonadal Steroid Hormones; Estrogens; Myocardial Infarction; Testosterone; United Kingdom
PubMed: 37730580
DOI: 10.1186/s13293-023-00546-3 -
European Journal of Preventive... Nov 2023Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global...
AIMS
Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults.
METHODS AND RESULTS
Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, there were 1235 global CVD events, 530 AF events, and 1173 deaths. Higher IL-6 [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.44-1.72 per log unit increase] and IL-18 (HR 1.13, 95% CI 1.01-1.26) were significantly associated with global CVD after adjustment for cardiovascular risk factors. Association between IL-6 and global CVD remained significant after further adjustment for high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT) but was no longer significant for IL-18 after further adjustments. Interleukin-6 was also associated with increased risk for CHD, HF, and AF after adjustment for covariates. Both IL-6 and IL-18 were associated with increased risk for all-cause death independent of cardiovascular risk factors and other biomarkers.
CONCLUSION
Among older adults, both IL-6 and IL-18 were associated with global CVD and death. The association between IL-6 with CVD appears to be more robust and was independent of hs-CRP, NT-proBNP, and hs-TnT.
Topics: Aged; Aged, 80 and over; Humans; Atherosclerosis; Atrial Fibrillation; Biomarkers; Brain Ischemia; C-Reactive Protein; Cardiovascular Diseases; Coronary Disease; Heart Failure; Interleukin-18; Interleukin-6; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors; Stroke
PubMed: 37306504
DOI: 10.1093/eurjpc/zwad197 -
BMC Genomics Mar 2024Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase... (Observational Study)
Observational Study
BACKGROUND
Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear.
METHODS
A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association.
RESULTS
In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively.
CONCLUSIONS
Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.
Topics: Humans; Atrial Fibrillation; Risk Factors; Magnesium; Mendelian Randomization Analysis; Calcium; Potassium; Phosphates; Electrolytes; Genome-Wide Association Study
PubMed: 38493091
DOI: 10.1186/s12864-024-10197-2