-
PloS One 2023Atherosclerosis and consequent risk of cardiovascular events or mortality can be accurately assessed by quantifying coronary artery calcium score (CACS) derived from...
BACKGROUND
Atherosclerosis and consequent risk of cardiovascular events or mortality can be accurately assessed by quantifying coronary artery calcium score (CACS) derived from computed tomography. HMG-CoA-reductase inhibitors (statins) are the primary pharmacotherapy used to reduce cardiovascular events, yet there is growing data that support statin use may increase coronary calcification. We set out to determine the likelihood of severe CACS in the context of chronic statin therapy.
METHODS
We established a retrospective, case-control study of 1,181 U.S. veterans without coronary artery disease (CAD) from a single site, the Providence VA Medical Center. Duration of statin therapy for primary prevention was divided into 5-year categorical increments. The primary outcome was CACS derived from low-dose lung cancer screening computed tomography (LCSCT), stratified by CACs severity (none = 0; mild = 1-99; moderate = 100-399; and severe ≥400 AU). Statin duration of zero served as the referent control. Ordinal logistic regression analysis determined the association between duration of statin use and CACS categories. Proportional odds assumption was tested using likelihood ratio test. Atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index, and CKD (glomerular filtration rate of <60 ml/min/1.73 m2) were included in the adjustment models.
RESULTS
The mean age of the study population was 64.7±7.2 years, and 706 (60%) patients were prescribed a statin at baseline. Duration of statin therapy was associated with greater odds of having increased CACS (>0-5 years, OR: 1.71 [CI: 1.34-2.18], p<0.001; >5-10 years, OR: 2.80 [CI: 2.01-3.90], p<0.001; >10 years, OR: 5.30 [CI: 3.23-8.70], p<0.001), and the relationship between statin duration and CACS remained significant after multivariate adjustment (>0-5 years, OR: 1.49 [CI: 1.16-1.92], p = 0.002; >5-10 years, OR: 2.38 [CI: 1.7-3.35], p<0.001; >10 years, OR: 4.48 [CI: 2.7-7.43], p<0.001).
CONCLUSIONS
Long-term use of statins is associated with increased likelihood of severe CACS in patients with significant smoking history. The use of CACS to interpret cardiovascular event risk may require adjustment in the context of chronic statin therapy.
Topics: Humans; Middle Aged; Aged; Coronary Artery Disease; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Retrospective Studies; Case-Control Studies; Early Detection of Cancer; Coronary Angiography; Lung Neoplasms; Atherosclerosis; Risk Factors; Vascular Calcification; Risk Assessment
PubMed: 37498869
DOI: 10.1371/journal.pone.0289111 -
GeroScience Dec 2023Chronic, low-level systemic inflammation associated with aging, or inflammaging, is a risk factor for several chronic diseases and mortality. Using data from the Health...
Chronic, low-level systemic inflammation associated with aging, or inflammaging, is a risk factor for several chronic diseases and mortality. Using data from the Health and Retirement Study, we generated a continuous latent variable for systemic inflammation from seven measured indicators of inflammation and examined associations with another biomarker of biological aging, DNA methylation age acceleration measured by epigenetic clocks, and 4-year mortality (N = 3,113). We found that greater systemic inflammation was positively associated with DNA methylation age acceleration for 10 of the 13 epigenetic clocks, after adjustment for sociodemographics and chronic disease risk factors. The latent variable for systemic inflammation was associated with 4-year mortality independent of DNA methylation age acceleration and was a better predictor of 4-year mortality than any of the epigenetic clocks examined, as well as mortality risk factors, including obesity and multimorbidity. Inflammaging and DNA methylation age acceleration may represent different biological processes contributing to mortality risk. Leveraging multiple measured inflammation markers to capture inflammaging is important for biology of aging research.
Topics: Humans; Epigenesis, Genetic; Retirement; Aging; DNA Methylation; Inflammation; Biomarkers
PubMed: 37501048
DOI: 10.1007/s11357-023-00880-9 -
Journal of Religion and Health Dec 2023Parkinson's disease (PD) is associated with low religiosity cross-sectionally. Whether low religiosity might be associated with an increased risk for developing PD is...
Parkinson's disease (PD) is associated with low religiosity cross-sectionally. Whether low religiosity might be associated with an increased risk for developing PD is unknown. This study investigated whether low religiosity in adulthood is associated with increased risk for developing PD. A population-based prospective cohort study was conducted. Participants from the English Longitudinal Study of Aging and the Midlife in the United States study who were free from PD at baseline (2004-2011) and completed questionnaires on self-reported religiosity, were included in a pooled analysis. Incident PD was based on self-report. Multivariable logistic regression was used to estimate odds ratios (OR) for developing PD according to baseline religiosity, with adjustment for sociodemographic characteristics, health and lifestyle factors and engagement in religious practices. Among 9,796 participants in the pooled dataset, 74 (0.8%) cases of incident PD were identified during a median follow-up of 8.1 years. In the fully adjusted model, compared with participants who considered religion very important in their lives at baseline, it was found that participants who considered religion "not at all important" in their lives had a tenfold risk of developing PD during follow-up (OR, 9.99; 95% CI 3.28-30.36). Moreover, there was a dose-response relationship between decreasing religiosity and increasing PD risk (P < 0.001 for trend). These associations were similar when adjusting for religious upbringing and when cases occurring within the first two years of follow-up were excluded from the analysis. The association was somewhat attenuated when religious practices were removed from the model as covariates, though it remained statistically significant (OR for "not at all important" vs. "very important", 2.26; 95% CI 1.03-4.95) (P < 0.029 for trend). This longitudinal study provides evidence for the first time that low religiosity in adulthood may be a strong risk factor for developing PD.
Topics: Humans; United States; Prospective Studies; Longitudinal Studies; Parkinson Disease; Religion; Risk Factors; Spirituality
PubMed: 35763200
DOI: 10.1007/s10943-022-01603-8 -
BMC Genomics Jul 2023Identifying reliable biomarkers could effectively predict esophagus carcinoma (EC) patients with poor prognosis. In this work, we constructed an immune-related gene...
BACKGROUND
Identifying reliable biomarkers could effectively predict esophagus carcinoma (EC) patients with poor prognosis. In this work, we constructed an immune-related gene pairs (IRGP) signature to evaluate the prognosis of EC.
RESULTS
The IRGP signature was trained by the TCGA cohort and validated by three GEO datasets, respectively. Cox regression model together with LASSO was applied to construct the overall survival (OS) associated IRGP. 21 IRGPs consisting of 38 immune-related genes were included in our signature, according to which patients were stratified into high- and low-risk groups. The results of Kaplan-Meier survival analyses indicated that high-risk EC patients had worse OS than low-risk group in the training set, meta-validation set and all independent validation datasets. After adjustment in multivariate Cox analyses, our signature continued to be an independent prognostic factor of EC and the signature-based nomogram could effectively predict the prognosis of EC sufferers. Besides, Gene Ontology analysis revealed this signature is related to immunity. 'CIBERSORT' analysis revealed the infiltration levels of plasma cells and activated CD4 memory T cells in two risk groups were significantly different. Ultimately, we validated the expression levels of six selected genes from IRGP index in KYSE-150 and KYSE-450.
CONCLUSIONS
This IRGP signature could be applied to select EC patients with high mortality risk, thereby improving prospects for the treatment of EC.
Topics: Humans; Esophageal Neoplasms; CD4-Positive T-Lymphocytes; Gene Ontology; Kaplan-Meier Estimate; Multivariate Analysis
PubMed: 37430202
DOI: 10.1186/s12864-023-09496-x -
Scientific Reports Aug 2023To evaluate the associations of periodontal disease (PD) with systemic diseases, including diabetes mellitus (DM) and cardiovascular disease (CVD), as well as the...
To evaluate the associations of periodontal disease (PD) with systemic diseases, including diabetes mellitus (DM) and cardiovascular disease (CVD), as well as the reciprocal association. The CVD included the cases of coronary heart disease and heart failure. A prospective study was conducted from 2007 to 2019 using linked data from three databases in Korea. Three separate study groups were formed to individually determine the risks of PD (n = 10,533), DM (n = 14,523) and CVD (n = 14,315). All diseases were confirmed based on physicians' diagnoses using medical records and self-reports. Cox proportional hazard regression was applied with 95% confidence intervals (CIs) to obtain hazard ratios (HRs). PD was significantly associated with an elevated risk of DM (HR [95% CI]: 1.22 [1.07-1.39]) after full adjustment for age, sex, lifestyle factors, body mass index, dental behaviour and CVD. PD was also found to increase the risk of CVD (1.27 [1.03-1.57]), whereas CVD increased the risk of PD (1.20 [1.09-1.32]) after full adjustment for other covariates including DM. This study found a bidirectional association between PD and CVD, as well as a positive association of PD with DM.
Topics: Humans; Prospective Studies; Periodontal Diseases; Cardiovascular Diseases; Heart Failure; Republic of Korea
PubMed: 37640779
DOI: 10.1038/s41598-023-41009-4 -
Schizophrenia Research. Cognition Sep 2024Schizophrenia spectrum disorders (SSD) are associated with pervasive cognitive impairments, including deficits in decision-making under risk. However, there is...
Schizophrenia spectrum disorders (SSD) are associated with pervasive cognitive impairments, including deficits in decision-making under risk. However, there is inconclusive evidence regarding specific mechanisms underlying altered decision-making patterns. In this study, participants (33 SSD and 28 non-SSD) completed the Columbia Card Task, an explicit risk-taking task, to better understand risk preference and adjustment in dynamic decision-making. We found that while there is no group difference in overall risk-taking, risk preference, or optimal decision-making, risk adjustment to contextual factors (e.g., loss probability) is blunted in SSD. We also found associations between risk-taking/suboptimal decision-making and disorganized symptoms, excited symptoms, and role functioning, but no associations between decision-making and working memory. These results suggest that during a complex, dynamic risk-taking task, individuals with SSD exhibit less adaption to changing information about risk, which may reflect risk imperception.
PubMed: 38764743
DOI: 10.1016/j.scog.2024.100314 -
Journal of the American Heart... Sep 2023Background Observational associations between type 2 diabetes (T2D) and atrial fibrillation (AF) have been established, but causality remains undetermined. We performed...
Background Observational associations between type 2 diabetes (T2D) and atrial fibrillation (AF) have been established, but causality remains undetermined. We performed Mendelian randomization (MR) to study causal effects of genetically predicted T2D on AF risk, independent of cardiometabolic risk factors. Methods and Results Instrumental variables included 182 uncorrelated single nucleotide polymorphisms associated with T2D at genome-wide significance ( <5×10). Genetic association estimates for cardiometabolic exposures were obtained from genome-wide association studies including 188 577 individuals for low-density lipoprotein-C, 694 649 individuals for body mass index, and 757 601 for systolic blood pressure. Two-sample, inverse-variance weighted MR formed the primary analyses. The MR-TRYX approach was used to dissect potential pleiotropic pathways, with multivariable MR performed to investigate cardiometabolic mediation. Genetically predicted T2D associated with increased AF liability in univariable MR (odds ratio [OR], 1.08 [95% CI, 1.02-1.13], =0.003). Sensitivity analyses indicated potential pleiotropy, with radial MR identifying 4 outlier single nucleotide polymorphisms that were likely contributors. Phenomic scanning on MR-base and subsequent least absolute shrinkage and selection operator regression allowed prioritization of 7 candidate traits. The outlier-adjusted effect estimate remained consistent with the original inverse-variance weighted estimate (OR, 1.07 [95% CI, 1.02-1.12], =0.008). On multivariable MR, T2D remained associated with increased AF liability after adjustment for low-density lipoprotein-C and body mass index. Following adjustment for systolic blood pressure, the relationship between T2D and AF became nonsignificant (OR, 1.04 [95% CI, 0.95-1.13], =0.40). Conclusions These data provide novel genetic evidence that while T2D likely causally associates with AF, mediation via systolic blood pressure exists. Endeavoring to lower systolic blood pressure alongside achieving normoglycemia may provide particular benefit on AF risk in patients with T2D.
Topics: Humans; Atrial Fibrillation; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Mendelian Randomization Analysis; Lipoproteins, LDL
PubMed: 37609985
DOI: 10.1161/JAHA.123.030298 -
Annals of Intensive Care Dec 2023Disseminated intravascular coagulation (DIC) worsens the prognosis of septic shock and contributes to multiple organ failure. To date, no data linking DIC and acute...
BACKGROUND
Disseminated intravascular coagulation (DIC) worsens the prognosis of septic shock and contributes to multiple organ failure. To date, no data linking DIC and acute kidney injury (AKI) occurrence, severity, and evolution in this setting are available. We aimed at analyzing the association between AKI occurrence, severity and evolution in patients with septic shock-induced DIC. In a prospective monocentric cohort study, consecutive patients, 18 years and older, admitted in the ICU of Strasbourg University Hospital in the setting of systemic hypotension requiring vasopressor related to an infection, without history of terminal chronic kidney disease were eligible. AKI was defined according to the KDIGO classification. DIC diagnosis was based on the International Society on Thrombosis and Haemostasis (ISTH) score. Evolution of AKI was evaluated through the composite endpoint of major adverse kidney events. Only patients with DIC that occurred before or at the time of AKI diagnosis were considered. Univariate and multivariate analysis were performed to determine factors associated with renal outcomes.
RESULTS
350 patients were included, of whom 129 experienced DIC. Patients with DIC were more seriously ill (median SAPS II 64 vs. 56, p < 0.001), and had higher 28-day mortality (43.3% vs. 26.2%, p < 0.001). AKI was more frequent in patients with DIC (86.8% vs. 74.2%, p < 0.005), particularly for the more severe stage of AKI [KDIGO 3 in 58.1% of patients with DIC vs. 30.8% of patients without DIC, p < 0.001, AKI requiring renal replacement therapy (RRT) in 47.3% of patients with DIC vs. 21.3% of patients without DIC, p < 0.001]. After adjustment for confounding factors, DIC occurrence remained associated with the risk of having the more severe stage of AKI with an odds ratio (OR) of 2.74 [IC 95% (1.53-4.91), p < 0.001], and with the risk of requiring RRT during the ICU stay [OR 2.82 (1.53-5.2), p < 0.001].
CONCLUSION
DIC appears to be strongly associated with the risk of developing the more severe form of AKI (stage 3 of the KDIGO classification, RRT requirement), even after adjustment for severity and other relevant factors.
PubMed: 38038826
DOI: 10.1186/s13613-023-01216-8 -
Epigenetics Dec 2023Occupational characteristics have been studied as risk factors for several age-related diseases and are thought to impact the ageing process, although there has been...
Occupational characteristics have been studied as risk factors for several age-related diseases and are thought to impact the ageing process, although there has been limited empirical work demonstrating an association between adverse occupational characteristics and accelerated ageing and this prior work has yielded mixed results. We used the 2010 and 2016 waves of the Health and Retirement Study ( = 1,251) to examine the association between occupation categories and self-reported working conditions of American adults at midlife and their subsequent epigenetic ageing as measured through five epigenetic clocks: PCHorvath, PCHannum, PCPhenoAge, PCGrimAge, and DunedinPACE. We found that individuals working in sales/clerical, service, and manual work show evidence of epigenetic age acceleration compared to those working in managerial/professional jobs and that the associations were stronger with second- and third-generation clocks. Individuals reporting high stress and high physical effort at work showed evidence of epigenetic age acceleration only on PCGrimAge and DunedinPACE. Most of these associations were attenuated after adjustment for race/ethnicity, educational attainment, and lifestyle-related risk factors. Sales/clerical work remained significantly associated with PCHorvath and PCHannum, while service work remained significantly associated with PCGrimAge. The results suggest that manual work and occupational physical activity may appear to be risk factors for epigenetic age acceleration through their associations with socioeconomic status, while stress at work may be a risk factor for epigenetic age acceleration through its associations with health behaviours outside of work. Additional work is needed to understand when in the life course and the specific mechanisms through which these associations occur.
Topics: Humans; United States; Aged; DNA Methylation; Aging; Ethnicity; Epigenesis, Genetic
PubMed: 37300823
DOI: 10.1080/15592294.2023.2218763 -
Frontiers in Endocrinology 2023To investigate whether prior cholecystectomy is associated with incident osteoporosis.
OBJECTIVE
To investigate whether prior cholecystectomy is associated with incident osteoporosis.
BACKGROUND
Cholecystectomy may have consequences involving abnormal metabolism. Studies investigating the association between prior cholecystectomy and osteoporosis have yielded inconsistent results.
METHODS
In total, 17,603 UK Biobank participants underwent cholecystectomy, and 35,206 matched controls were included in this study. They were followed up for incident osteoporosis, which was determined using ICD-10 codes (M80-82). The association between cholecystectomy and osteoporosis was assessed using Cox proportional regression modeling. The association between osteoporosis risk and cholecystectomy was further analyzed across age, sex, serum vitamin D level, and body mass index (BMI) categories.
RESULTS
Within a median follow-up period of 13.56 years, 3,217 participants were diagnosed with osteoporosis. After adjustment for relevant confounders, prior cholecystectomy was associated with a 1.21 times higher risk of osteoporosis in women (hazard ratio (HR): 1.21 [95% CI, 1.12-1.31], p < 0.001) and a 1.45 times higher risk in men (HR: 1.45 [95% CI, 1.10-1.90], p = 0.007). In women, the association was stronger for patients who were aged 40-55 years, with BMI < 18.5 kg/m, and vitamin D between 30 and 50 nmol/ml. No significant interactions between cholecystectomy and income level, education level, presence of hypertension, or diabetes were identified in either sex.
CONCLUSIONS
Our findings indicated that people who underwent cholecystectomy had a higher risk of developing osteoporosis after adjustment for potential confounders. Our findings suggest that awareness of the risk of osteoporosis in patients with a history of cholecystectomy is merited.
Topics: Male; Humans; Female; Prospective Studies; Biological Specimen Banks; Osteoporosis; Vitamin D; Cholecystectomy; United Kingdom
PubMed: 37929032
DOI: 10.3389/fendo.2023.1259475