scholarly journals The epigenetic etiology of cardiovascular disease in a longitudinal Swedish twin study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xueying Qin ◽  
Ida K. Karlsson ◽  
Yunzhang Wang ◽  
Xia Li ◽  
Nancy Pedersen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cvd Risk ◽  
Significance Level ◽  
Latent Trajectory ◽  
Lagged Effects ◽  
The Cross ◽  
Level 2 ◽  
Cardiometabolic Traits

Abstract Background Studies on DNA methylation have the potential to discover mechanisms of cardiovascular disease (CVD) risk. However, the role of DNA methylation in CVD etiology remains unclear. Results We performed an epigenome-wide association study (EWAS) on CVD in a longitudinal sample of Swedish twins (535 individuals). We selected CpGs reaching the Bonferroni-corrected significance level (2 $$\times$$ ×  10–7) or the top-ranked 20 CpGs with the lowest P values if they did not reach this significance level in EWAS analysis associated with non-stroke CVD, overall stroke, and ischemic stroke, respectively. We further applied a bivariate autoregressive latent trajectory model with structured residuals (ALT-SR) to evaluate the cross-lagged effect between DNA methylation of these CpGs and cardiometabolic traits (blood lipids, blood pressure, and body mass index). Furthermore, mediation analysis was performed to evaluate whether the cross-lagged effects had causal impacts on CVD. In the EWAS models, none of the CpGs we selected reached the Bonferroni-corrected significance level. The ALT-SR model showed that DNA methylation levels were more likely to predict the subsequent level of cardiometabolic traits rather than the other way around (numbers of significant cross-lagged paths of methylation → trait/trait → methylation were 84/4, 45/6, 66/1 for the identified three CpG sets, respectively). Finally, we demonstrated significant indirect effects from DNA methylation on CVD mediated by cardiometabolic traits. Conclusions We present evidence for a directional association from DNA methylation on cardiometabolic traits and CVD, rather than the opposite, highlighting the role of epigenetics in CVD development.

scholarly journals Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial

2016 ◽  
Vol 62 (4) ◽  
pp. 582-592 ◽  
Author(s):  
Miguel Ruiz-Canela ◽  
Estefania Toledo ◽  
Clary B Clish ◽  
Adela Hruby ◽  
Liming Liang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Amino Acids ◽  
Cardiovascular Death ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Cvd Risk ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Branched Chain

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05–2.76) and 2.09 (1.27–3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.

scholarly journals Serum Bilirubin and Genes Controlling Bilirubin Concentrations as Biomarkers for Cardiovascular Disease

2010 ◽  
Vol 56 (10) ◽  
pp. 1535-1543 ◽  
Author(s):  
Jing-Ping Lin ◽  
Libor Vitek ◽  
Harvey A Schwertner
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Serum Bilirubin ◽  
Association Studies ◽  
Major Gene ◽  
Linkage Study ◽  
Cvd Risk ◽  
Related Factors ◽  
Genetic Interventions

BACKGROUND Serum bilirubin has been consistently shown to be inversely related to cardiovascular disease (CVD). Recent studies showed serum bilirubin to be associated with CVD-related factors such as diabetes, metabolic syndrome, and body mass index. Although the association of serum bilirubin with CVD has been found in both retrospective and prospective studies, less information is available on the role of genes that control bilirubin concentrations and their association with CVD. CONTENT In this review, we provide detailed information on the identity of the major genes that control bilirubin concentrations and their association with serum bilirubin concentrations and CVD risk. We also update the results of the major studies that have been performed on the association between serum bilirubin, CVD, and CVD-related diseases such as diabetes or metabolic syndrome. Studies consistently indicate that bilirubin concentrations are inversely associated with different types of CVD and CVD-related diseases. A conditional linkage study indicates that UGT1A1 is the major gene controlling serum bilirubin concentrations, and this finding has been confirmed in recent genomewide association studies. Studies also indicate that individuals homozygous for UGT1A1*28 have a significantly lower risk of developing CVD than carriers of the wild-type alleles. SUMMARY Serum bilirubin has a protective effect on CVD and CVD-related diseases, and UGT1A1 is the major gene controlling serum bilirubin concentrations. Pharmacologic, nonpharmacologic, or genetic interventions that increase serum bilirubin concentrations could provide more direct evidence on the role of bilirubin in CVD prevention.

scholarly journals A neurobiological mechanism linking transportation noise to cardiovascular disease in humans

2019 ◽  
Vol 41 (6) ◽  
pp. 772-782 ◽  
Author(s):  
Michael T Osborne ◽  
Azar Radfar ◽  
Malek Z O Hassan ◽  
Shady Abohashem ◽  
Blake Oberfeld ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Activity ◽  
Noise Exposure ◽  
Underlying Mechanism ◽  
Cvd Risk ◽  
Stress Perception ◽  
Transportation Noise ◽  
Positron Emission ◽  
Arterial Inflammation

Abstract Aims Chronic noise exposure associates with increased cardiovascular disease (CVD) risk; however, the role of confounders and the underlying mechanism remain incompletely defined. The amygdala, a limbic centre involved in stress perception, participates in the response to noise. Higher amygdalar metabolic activity (AmygA) associates with increased CVD risk through a mechanism involving heightened arterial inflammation (ArtI). Accordingly, in this retrospective study, we tested whether greater noise exposure associates with higher: (i) AmygA, (ii) ArtI, and (iii) risk for major adverse cardiovascular disease events (MACE). Methods and results Adults (N = 498) without CVD or active cancer underwent clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Amygdalar metabolic activity and ArtI were measured, and MACE within 5 years was adjudicated. Average 24-h transportation noise and potential confounders were estimated at each individual’s home address. Over a median 4.06 years, 40 individuals experienced MACE. Higher noise exposure (per 5 dBA increase) predicted MACE [hazard ratio (95% confidence interval, CI) 1.341 (1.147–1.567), P < 0.001] and remained robust to multivariable adjustments. Higher noise exposure associated with increased AmygA [standardized β (95% CI) 0.112 (0.051–0.174), P < 0.001] and ArtI [0.045 (0.001–0.090), P = 0.047]. Mediation analysis suggested that higher noise exposure associates with MACE via a serial mechanism involving heightened AmygA and ArtI that accounts for 12–26% of this relationship. Conclusion Our findings suggest that noise exposure associates with MACE via a mechanism that begins with increased stress-associated limbic (amygdalar) activity and includes heightened arterial inflammation. This potential neurobiological mechanism linking noise to CVD merits further evaluation in a prospective population.

scholarly journals 1062 The Role of Sleep in Sex and Racial/Ethnic Differences in 10-Year CVD Risk in the Sleep Heart Health Study: The Use of Machine-Learnt and Precision Insights to Understand Racial/Ethnic and Sex Differences in Sleep-CVD Disparity

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A403-A405
Author(s):  
A Seixas ◽  
P Jin ◽  
M Liu ◽  
J Nunes ◽  
M Grandner ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Risk Groups ◽  
Health Study ◽  
Cvd Risk ◽  
Cluster Analyses ◽  
Blacks And Whites ◽  
Level 1 ◽  
Racial Ethnic ◽  
Level 2

Abstract Introduction The current study investigated whether insufficient sleep (<7 hrs.) explains differences in 10-year CVD risk, using Framingham risk (FRS) and Reynolds risk (RRS) scores, between blacks and whites and characterized risk and protective CVD risk profiles. Methods Using the Sleep Heart Health Study (SHHS) (N=6,441) data, we investigated the independent role of insufficient sleep in explaining differences in 10-years CVD between blacks and whites via a proportional odds model of four 10-year CVD risk groups: low (<5%), low-medium (5% to <10%), medium-high (10% to <20%) and high (≥20%), adjusting for age, sex, and apnea-hypopnea index (AHI). We performed two levels of cluster analyses; via hierarchical cluster algorithm with entire sample (Level 1), and latent profiles in the low (protective profiles) and high (risk profiles) CVD risk groups (Level 2) to determine overall CVD risk, and risk and protective CVD profiles. Results Blacks had a higher prevalence of smoking behavior, diabetes, mean systolic blood pressure, body mass index, total cholesterol compared to whites. Conversely, whites had a higher mean HDL cholesterol, sleep hours, and sleep efficiency compared to blacks. Men had higher 10-year CVD risk than women. AHI and race/ethnicity-sleep interaction were positively associated, while sleep was negatively associated with FRS and RRS. Across all CVD risk groups, whites who slept less than 5.5 hrs. had a higher CVD risk and those who slept more than 6.5 hrs. had a lower CVD risk compared to blacks. In Level 1 cluster analyses, we found two clusters: Cluster 1 (n= 3233): 6.17 sleep hours, apnea-index 11.84, age 59, SBP 125.43, total cholesterol 209, HDL 51.39, BMI 29.03, and slightly more than 50% female; and Cluster 2 (n=1657): 5.61 sleep hours, apnea-index 13.41, age 74, SBP 131, total cholesterol 204, HDL 50.30, BMI 26.45, and slightly less than 50% female. In Level 2 cluster analyses, we found two profiles within the low and high CVD risk groups. Conclusion These findings suggest that blacks may not receive full protection from long-term CVD risk with longer sleep duration, as their white counterparts. Support K01HL135452, R01MD007716, R01HL142066, K07AG052685

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

2018 ◽  
Vol 24 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Peter Riis Hansen
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Inflammatory Diseases ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Chronic Inflammatory Diseases ◽  
Increased Risk ◽  
Shared Risk

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD.

scholarly journals Role of Testosterone in the Treatment of Cardiovascular Disease

2017 ◽  
Vol 12 (02) ◽  
pp. 1 ◽  
Author(s):  
Carolyn M Webb ◽  
Peter Collins ◽  
◽  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular System ◽  
Serum Testosterone ◽  
Current Evidence ◽  
Premature Coronary Artery Disease ◽  
Cvd Risk ◽  
Testosterone Levels ◽  
Increased Risk

Cardiovascular disease (CVD) is the most prevalent non-communicable cause of death worldwide. Testosterone is a sex hormone that is predominant in males but also occurs in lower concentrations in females. It has effects directly on the blood vessels of the cardiovascular system and on the heart, as well as effects on risk factors for CVD. Serum testosterone concentrations are known to decrease with age and reduced testosterone levels are linked to premature coronary artery disease, unfavourable effects on CVD risk factors and increased risk of cardiovascular mortality independent of age. A significant number of men with heart failure demonstrate reduced serum testosterone concentrations and there is early evidence suggesting that low testosterone levels affect cardiac repolarisation. Any association between endogenous testosterone concentrations and CVD in women has yet to be established. Testosterone replacement is used to treat men with hypogonadism but also has cardiovascular effects. This review will present the current evidence, expert opinion and controversies around the role of testosterone in the pathophysiology of CVD and surrounding the use of testosterone treatment and its effects on the cardiovascular system and CVD.

scholarly journals Epigenetic Age Acceleration in Adolescence Associates With BMI, Inflammation, and Risk Score for Middle Age Cardiovascular Disease

2019 ◽  
Vol 104 (7) ◽  
pp. 3012-3024 ◽  
Author(s):  
Rae-Chi Huang ◽  
Karen A Lillycrop ◽  
Lawrence J Beilin ◽  
Keith M Godfrey ◽  
Denise Anderson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Middle Age ◽  
Accelerated Aging ◽  
Model Assessment ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration

Abstract Context “Accelerated aging,” assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age. Design DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA; preserved across cell types) and extrinsic (EEAA; dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors [lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers] were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development. Results In 995 participants (49.6% female; age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ–inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors. Conclusions Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction.

scholarly journals Relating Education, Brain Structure, and Cognition: The Role of Cardiovascular Disease Risk Factors

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Moyra E. Mortby ◽  
Richard Burns ◽  
Andrew L. Janke ◽  
Perminder S. Sachdev ◽  
Kaarin J. Anstey ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Protective Effect ◽  
Disease Risk ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Cerebral Structure ◽  
Mediating Role ◽  
Brain Ageing

The protective effect of education on cognitive and brain health is well established. While the direct effects of individual cardiovascular disease (CVD) risk factors (i.e., hypertension, smoking, diabetes, and obesity) on cerebral structure have been investigated, little is understood about the possible interaction between the protective effect of education and the deleterious effects of CVD risk factors in predicting brain ageing and cognition. Using data from the PATH Through Life study(N=266), we investigated the protective effect of education on cerebral structure and function and tested a possible mediating role of CVD risk factors. Higher education was associated with larger regional grey/white matter volumes in the prefrontal cortex in men only. The association between education and cognition was mediated by brain volumes but only for grey matter and only in relation to information processing speed. CVD risk factors did not mediate the association between regional volumes and cognition. This study provides additional evidence in support for a protective effect of education on cerebral structures and cognition. However, it does not provide support for a mediating role of CVD risk factors in these associations.

scholarly journals Cardiovascular Complications in CKD Patients: Role of Oxidative Stress

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Elvira O. Gosmanova ◽  
Ngoc-Anh Le
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Kidney Failure ◽  
Physical Inactivity ◽  
Chronic Kidney Failure ◽  
Cardiovascular Complications ◽  
Cvd Risk Factors ◽  
Cvd Risk

Starting with the early stages, patients with chronic kidney disease (CKD) experience higher burden of cardiovascular disease (CVD). Moreover, CVD complications are the major cause of mortality in CKD patients as compared with complications from chronic kidney failure. While traditional CVD risk factors, including diabetes, hypertension, hyperlipidemia, obesity, physical inactivity, may be more prevalent among CKD patients, these factors seem to underestimate the accelerated cardiovascular disease in the CKD population. Search for additional biomarkers that could explain the enhanced CVD risk in CKD patients has gained increasing importance. Although it is unlikely that any single nontraditional risk factor would fully account for the increased CVD risk in individuals with CKD, oxidative stress appears to play a central role in the development and progression of CVD and its complications. We will review the data that support the contribution of oxidative stress in the pathogenesis of CVD in patients with chronic kidney failure.

scholarly journals The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease

2015 ◽  
Vol 75 (3) ◽  
pp. 560-565 ◽  
Author(s):  
Elena Myasoedova ◽  
Arun Chandran ◽  
Birkan Ilhan ◽  
Brittny T Major ◽  
C John Michet ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Moving Average ◽  
Population Based ◽  
Cvd Risk ◽  
Cox Models ◽  
Lower Tertile ◽  
American College Of Rheumatology ◽  
Index Of Severity

ObjectiveTo examine the role of rheumatoid arthritis (RA) flare, remission and RA severity burden in cardiovascular disease (CVD).MethodsIn a population-based cohort of patients with RA without CVD (age ≥30 years; 1987 American College of Rheumatology criteria met in 1988–2007), we performed medical record review at each clinical visit to estimate flare/remission status. The previously validated RA medical Records-Based Index of Severity (RARBIS) and Claims-Based Index of RA Severity (CIRAS) were applied. Age- and sex-matched non-RA subjects without CVD comprised the comparison cohort. Cox models were used to assess the association of RA activity/severity with CVD, adjusting for age, sex, calendar year of RA, CVD risk factors and antirheumatic medications.ResultsStudy included 525 patients with RA and 524 non-RA subjects. There was a significant increase in CVD risk in RA per time spent in each acute flare versus remission (HR 1.07 per 6-week flare, 95% CI 1.01 to 1.15). The CVD risk for patients with RA in remission was similar to the non-RA subjects (HR 0.90, 95% CI 0.51 to 1.59). Increased cumulative moving average of daily RARBIS (HR 1.16, 95% CI 1.03 to 1.30) and CIRAS (HR 1.38, 95% CI 1.12 to 1.70) was associated with CVD. CVD risk was higher in patients with RA who spent more time in medium (HR 1.08, 95% CI 0.98 to 1.20) and high CIRAS tertiles (HR 1.18, 95% CI 1.06 to 1.31) versus lower tertile.ConclusionsOur findings show substantial detrimental role of exposure to RA flare and cumulative burden of RA disease severity in CVD risk in RA, suggesting important cardiovascular benefits associated with tight inflammation control and improved flare management in patients with RA.

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