Cardiovascular Risk Factor Control and Lifestyle Factors in Young to Middle-Aged Adults with Newly Diagnosed Obstructive Coronary Artery Disease.
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ABSTRACT:
SUBMITTER: Garshick MS
PROVIDER: S-EPMC6668015 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. Vascular expression and activity of TNFa convertase enzyme were preserved in aging. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly.
2010-06-05 | E-GEOD-619 | biostudies-arrayexpress
Project description:Background: Epidemiological characteristics and prognostic profiles of patients with newly diagnosed coronary artery disease (CAD) are heterogeneous. Therefore, providing individualized cardiovascular (CV) risk stratification and tailored prevention is crucial. Objective: Phenotypic unsupervised clustering integrating clinical, coronary computed tomography angiography (CCTA), and cardiac magnetic resonance (CMR) data were used to unveil pathophysiological differences between subgroups of patients with newly diagnosed CAD. Materials and Methods: Between 2008 and 2020, consecutive patients with newly diagnosed obstructive CAD on CCTA and further referred for vasodilator stress CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or non-fatal myocardial infarction. For this exploratory work, a cluster analysis was performed on clinical, CCTA, and CMR variables, and associations between phenogroups and outcomes were assessed. Results: Among 2,210 patients who underwent both CCTA and CMR, 2,015 (46% men, mean 70 ± 12 years) completed follow-up [median 6.8 (IQR 5.9-9.2) years], in which 277 experienced a MACE (13.7%). Three mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: (PG1) CAD in elderly patients with few traditional risk factors; (PG2) women with metabolic syndrome, calcified plaques on CCTA, and preserved left ventricular ejection fraction (LVEF); (PG3) younger men smokers with proximal non-calcified plaques on CCTA, myocardial scar, and reduced LVEF. Using survival analysis, the occurrence of MACE, cardiovascular mortality, and all-cause mortality (all p < 0.001) differed among the three PG, in which PG3 had the worse prognosis. In each PG, inducible ischemia was associated with MACE [PG1, Hazards Ratio (HR) = 3.09, 95% CI, 1.70-5.62; PG2, HR = 3.62, 95% CI, 2.31-5.7; PG3, HR = 3.55, 95% CI, 2.3-5.49; all p < 0.001]. The study presented some key limitations that may impact generalizability. Conclusions: Cluster analysis of clinical, CCTA, and CMR variables identified three phenogroups of patients with newly diagnosed CAD that were associated with distinct clinical and prognostic profiles. Inducible ischemia assessed by stress CMR remained associated with the occurrence of MACE within each phenogroup. Whether automated unsupervised phenogrouping of CAD patients may improve clinical decision-making should be further explored in prospective studies.
| S-EPMC8636934 | biostudies-literature
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. Vascular expression and activity of TNFa convertase enzyme were preserved in aging. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly. Keywords: other
2003-10-28 | GSE619 | GEO
Project description:BACKGROUND:A low cardiovascular disease risk profile (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, never smoking, and no history of diabetes mellitus or myocardial infarction) in middle age is associated with markedly better health outcomes in older age, but few middle-aged adults have this low risk profile. We examined whether adopting a healthy lifestyle throughout young adulthood is associated with the presence of the low cardiovascular disease risk profile in middle age. METHODS AND RESULTS:The Coronary Artery Risk Development in (Young) Adults (CARDIA) study sample consisted of 3154 black and white participants 18 to 30 years of age at year 0 (1985-1986) who attended the year 0, 7, and 20 examinations. Healthy lifestyle factors defined at years 0, 7, and 20 included average body mass index <25 kg/m(2), no or moderate alcohol intake, higher healthy diet score, higher physical activity score, and never smoking. Mean age (25 years) and percentage of women (56%) were comparable across groups defined by number of healthy lifestyle factors. The age-, sex-, and race-adjusted prevalences of low cardiovascular disease risk profile at year 20 were 3.0%, 14.6%, 29.5%, 39.2%, and 60.7% for people with 0 or 1, 2, 3, 4, and 5 healthy lifestyle factors, respectively (P for trend <0.0001). Similar graded relationships were observed for each sex-race group (all P for trend <0.0001). CONCLUSIONS:Maintaining a healthy lifestyle throughout young adulthood is strongly associated with a low cardiovascular disease risk profile in middle age. Public health and individual efforts are needed to improve the adoption and maintenance of healthy lifestyles in young adults.
| S-EPMC3353808 | biostudies-literature
Project description:ObjectiveControversy exists about the coronary artery disease (CAD) risk conveyed by diabetes in young and middle-aged women. We investigated sex differences in CAD by diabetes status among healthy individuals with different underlying risks of heart disease.Research design and methodsWe examined subjects aged <60 years without CAD at enrollment in the high-risk GeneSTAR Study (n = 1,448; follow-up ?12 years), Multi-Ethnic Study of Atherosclerosis (MESA; n = 3,072; follow-up ?7 years), and National Health and Nutrition Examination Survey III (NHANES III) Mortality Follow-up Study (n = 6,997; follow-up ?15 years). Diabetes was defined by report, hypoglycemic use, and/or fasting glucose ?126 mg/dL. The outcome was any CAD event during follow-up (fatal CAD in NHANES).ResultsIn the absence of diabetes, CAD rates were lower among women in GeneSTAR, MESA, and NHANES (4.27, 1.66, and 0.40/1,000 person-years, respectively) versus men (11.22, 5.64, and 0.88/1,000 person-years); log-rank P < 0.001 (GeneSTAR/MESA) and P = 0.07 (NHANES). In the presence of diabetes, CAD event rates were similar among women (17.65, 7.34, and 2.37/1,000 person-years) versus men (12.86, 9.71, and 1.83/1,000 person-years); all log-rank P values > 0.05. Adjusting for demographics, diabetes was associated with a significant four- to fivefold higher CAD rate among women in each cohort, without differences in men. In meta-analyses of three cohorts, additionally adjusted for BMI, smoking, hypertension, HDL, and non-HDL cholesterol, antihypertensive and cholesterol-lowering medication use, the hazard ratio of CAD in men versus women among nondiabetes was 2.43 (1.76-3.35) and diabetes was 0.89 (0.43-1.83); P = 0.013 interaction by diabetes status.ConclusionsThough young and middle-aged women are less likely to develop CAD in the absence of diabetes, the presence of diabetes equalizes the risk by sex. Our findings support aggressive CAD prevention strategies in women with diabetes and at similar levels to those that exist in men.
| S-EPMC3931379 | biostudies-literature
Project description:BackgroundFew studies to date have described the prevalence of electrocardiographic (ECG) abnormalities in a biracial middle-aged cohort.Methods and resultsParticipants underwent measurement of traditional risk factors and 12-lead ECGs coded using both Minnesota Code and Novacode criteria. Among 2585 participants, of whom 57% were women and 44% were black (mean age 45 years), the prevalence of major and minor abnormalities was significantly higher (all P < .001) among black men and women compared to whites. These differences were primarily due to higher QRS voltage and ST/T-wave abnormalities among blacks. There was also a higher prevalence of Q waves (Minnesota Code 1-1, 1-2, 1-3) than described by previous studies. These racial differences remained after multivariate adjustment for traditional cardiovascular (CV) risk factors.ConclusionsBlack men and women have a significantly higher prevalence of ECG abnormalities, independent of traditional cardiovascular risk factors, than whites in a contemporary cohort of middle-aged participants.
| S-EPMC3569004 | biostudies-literature
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (microarray, real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly. Keywords: repeat sample
2003-10-28 | GSE615 | GEO
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. Vascular expression and activity of TNFa convertase enzyme were preserved in aging. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly. Keywords: repeat sample
2003-10-28 | GSE616 | GEO
Project description:Type 2 diabetes mellitus (T2DM) is well known for its adverse impacts on brain and cognition, which leads to multidimensional cognitive deficits and wildly spread cerebral structure abnormalities. However, existing literatures are mainly focused on patients with advanced age or extended T2DM duration. Therefore, it remains unclear whether and how brain function would be affected at the initial onset stage of T2DM in relatively younger population. In current study, twelve newly diagnosed middle-aged T2DM patients with no previous diabetic treatment history and twelve matched controls were recruited. Brain activations during a working memory task, the digit n-back paradigm (0-, 1- and 2-back), were obtained with functional magnetic resonance imaging and tested by repeated measures ANOVA. Whereas patients performed the n-back task comparably well as controls, significant load-by-group interactions of brain activation were found in the right dorsolateral prefrontal cortex (DLPFC), left middle/inferior frontal gyrus, and left parietal cortex, where patients exhibited hyperactivation in the 2-back, but not the 0-back or 1-back condition compared to controls. Furthermore, the severity of chronic hyperglycemia, estimated by glycosylated hemoglobin (HbA1c) level, was entered into partial correlational analyses with task-related brain activations, while controlling for the real-time influence of glucose, estimated by instant plasma glucose level measured before scanning. Significant positive correlations were found between HbA1c and brain activations in the anterior cingulate cortex and bilateral DLPFC only in patients. Taken together, these findings suggest there might be a compensatory mechanism due to brain inefficiency related to chronic hyperglycemia at the initial onset stage of T2DM.
| S-EPMC4416650 | biostudies-literature
Project description:ImportanceSteps per day is a meaningful metric for physical activity promotion in clinical and population settings. To guide promotion strategies of step goals, it is important to understand the association of steps with clinical end points, including mortality.ObjectiveTo estimate the association of steps per day with premature (age 41-65 years) all-cause mortality among Black and White men and women.Design, setting, and participantsThis prospective cohort study was part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants were aged 38 to 50 years and wore an accelerometer from 2005 to 2006. Participants were followed for a mean (SD) of 10.8 (0.9) years. Data were analyzed in 2020 and 2021.ExposureDaily steps volume, classified as low (<7000 steps/d), moderate (7000-9999 steps/d), and high (≥10 000 steps/d) and stepping intensity, classified as peak 30-minute stepping rate and time spent at 100 steps/min or more.Main outcomes and measuresAll-cause mortality.ResultsA total of 2110 participants from the CARDIA study were included, with a mean (SD) age of 45.2 (3.6) years, 1205 (57.1%) women, 888 (42.1%) Black participants, and a median (interquartile range [IQR]) of 9146 (7307-11 162) steps/d. During 22 845 person years of follow-up, 72 participants (3.4%) died. Using multivariable adjusted Cox proportional hazards models, compared with participants in the low step group, there was significantly lower risk of mortality in the moderate (hazard ratio [HR], 0.28 [95% CI, 0.15-0.54]; risk difference [RD], 53 [95% CI, 27-78] events per 1000 people) and high (HR, 0.45 [95% CI, 0.25-0.81]; RD, 41 [95% CI, 15-68] events per 1000 people) step groups. Compared with the low step group, moderate/high step rate was associated with reduced risk of mortality in Black participants (HR, 0.30 [95% CI, 0.14-0.63]) and in White participants (HR, 0.37 [95% CI, 0.17-0.81]). Similarly, compared with the low step group, moderate/high step rate was associated with reduce risk of mortality in women (HR, 0.28 [95% CI, 0.12-0.63]) and men (HR, 0.42 [95% CI, 0.20-0.88]). There was no significant association between peak 30-minute intensity (lowest vs highest tertile: HR, 0.98 [95% CI, 0.54-1.77]) or time at 100 steps/min or more (lowest vs highest tertile: HR, 1.38 [95% CI, 0.73-2.61]) with risk of mortality.Conclusions and relevanceThis cohort study found that among Black and White men and women in middle adulthood, participants who took approximately 7000 steps/d or more experienced lower mortality rates compared with participants taking fewer than 7000 steps/d. There was no association of step intensity with mortality.
| S-EPMC8417757 | biostudies-literature