A Vicious Circle of Clonal Haematopoiesis of Indeterminate Potential and Cardiovascular Disease

2021 ◽  
Vol 41 (06) ◽  
pp. 443-446
Author(s):  
Carolin A. Ehlert ◽  
Ingo Hilgendorf
Keyword(s):  
Cardiovascular Disease ◽  
Observational Studies ◽  
Experimental Studies ◽  
Vicious Circle ◽  
Driver Mutations ◽  
Cvd Risk ◽  
Genetic Studies ◽  
Increased Risk ◽  
Inflammatory Processes ◽  
Inflammatory Immune Response

AbstractClonal haematopoiesis of indeterminate potential (CHIP) represents a recently identified overlap between cancer and cardiovascular disease (CVD). CHIP develops as a result of certain acquired somatic mutations that predispose to leukaemia, but clinically even more prevalent, associate with increased risk for CVD and CVD-related death. Experimental studies suggest a causal role for CHIP aggravating inflammatory processes in CVD, and recent epidemiologic and genetic studies indicate that classical CVD risk factors may increase the risk of acquiring CHIP driver mutations, thus fuelling a vicious circle. The potential mechanism underlying the associative link between CHIP and CVD and mortality has been the focus of a few recent excellent experimental and observational studies which are summarized and discussed in this concise non-systematic review article. These data support a pathomechanistic view of a spiralling vicious circle in which CHIP aggravates the inflammatory immune response in CVD, and CVD-driven elevated haematopoietic activity promotes CHIP development.

Circulating Stem/Progenitor Cells as Prognostic Biomarkers in Macro- and Microvascular Disease: A Narrative Review of Prospective Observational Studies

2018 ◽  
Vol 25 (35) ◽  
pp. 4507-4517 ◽  
Author(s):  
Mauro Rigato ◽  
Gian Paolo Fadini
Keyword(s):  
Cardiovascular Disease ◽  
Progenitor Cells ◽  
Cardiovascular Events ◽  
Observational Studies ◽  
English Language ◽  
Microvascular Disease ◽  
Patient Characteristics ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Cell Phenotypes

Background: Circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) are immature cells involved in vascular repair and related to many aspects of macro and microvascular disease. <p> Objective: We aimed to review studies reporting the prognostic role of CPCs/EPCs measurement on development of cardiovascular disease and microangiopathy. <p> Methods and Results: We reviewed the English language literature for prospective observational studies reporting the future development of cardiovascular disease or microangiopathy in patients having a baseline determination of CPCs/EPCs. We retrieved 34 studied reporting on cardiovascular outcomes and 2 studies reporting on microvascular outcomes. Overall, a reduced baseline level of CPCs/EPCs was associated with a significant increased risk of cardiovascular events, all-cause death, and onset/progression of microangiopathy. The most predictive phenotypes were CD34+ and CD34+CD133+. The main limitation was related to the high heterogeneity among studies in terms of patient characteristics and cell phenotypes. <p> Conclusion: The present review shows that a reduced level of circulating progenitor cells is a risk factor for the development of future cardiovascular events and death. In addition, low CPCs/EPCs levels predict the onset or worsening of microalbuminuria and retinopathy in diabetic patients.

scholarly journals Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies

2021 ◽  
Vol 14 ◽  
pp. 117954412110287
Author(s):  
Mir Sohail Fazeli ◽  
Vadim Khaychuk ◽  
Keith Wittstock ◽  
Boris Breznen ◽  
Grace Crocket ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Literature Review ◽  
Rheumatoid Factor ◽  
Qualitative Evidence Synthesis ◽  
Cvd Risk ◽  
Rheumatoid Arthritis Risk ◽  
Published Evidence ◽  
Increased Risk

Objective: To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents. Methods: Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out. Results: A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients. Conclusion: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.

scholarly journals Vitamin D and Cardiovascular Disease: An Updated Narrative Review

2021 ◽  
Vol 22 (6) ◽  
pp. 2896
Author(s):  
Armin Zittermann ◽  
Christian Trummer ◽  
Verena Theiler-Schwetz ◽  
Elisabeth Lerchbaum ◽  
Winfried März ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Vitamin D ◽  
High Risk ◽  
General Population ◽  
Vitamin D Deficiency ◽  
Specific Gene ◽  
Vitamin D Status ◽  
Cvd Risk ◽  
Severe Vitamin ◽  
Increased Risk

During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.

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.

Aortic Root Diameter and Arterial Stiffness: Conjoint Relations to the Incidence of Cardiovascular Disease in the Framingham Heart Study

Hypertension ◽  
2021 ◽  
Author(s):  
Ramachandran S. Vasan ◽  
Rebecca J. Song ◽  
Vanessa Xanthakis ◽  
Gary F. Mitchell
Keyword(s):  
Cardiovascular Disease ◽  
Pulse Pressure ◽  
Aortic Root ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Root Diameter ◽  
Cvd Risk ◽  
Heart Study ◽  
Increased Risk ◽  
Central Pulse Pressure

Higher central pulse pressure is associated with higher carotid-femoral pulse wave velocity (CFPWV) and an increased risk of cardiovascular disease (CVD). A smaller aortic root diameter (AoR) is associated with higher central pulse pressure. We hypothesized that the combination of a smaller AoR and higher CFPWV is associated with increased CVD risk (relative to a larger AoR and lower CFPWV). We tested this hypothesis in the community-based Framingham Study (N=1970, mean age 60 years, 57% women). We created sex-specific longitudinal echocardiographic AoR trajectories over 2 decades, categorizing participants into smaller versus larger AoR groups. We cross-classified participants based on their AoR trajectory and CFPWV (dichotomized at the sex-specific median). We used Cox regression to relate the cross-classified groups to CVD incidence on follow-up (median 17 years): lower CFPWV, larger AoR (referent group; 6.4/1000 person-years); lower CFPWV, smaller AoR (6.9/1000 person-years); higher CFPWV, larger AoR (23.1/1000 person-years); and higher CFPWV, smaller AoR (21.9/1000 person-years). In sex-pooled analyses, groups with higher CFPWV were associated with a multivariable-adjusted 1.8-fold risk of CVD ( P <0.01) regardless of AoR size. We observed effect modification by sex ( P for sex×AoR-CFPWV group interaction 0.04). In men, the group with smaller AoR and higher CFPWV was associated with a 2.5- to 2.8-fold risk of CVD ( P <0.001). In women, the group with larger AoR and higher CFPWV experienced a statistically nonsignificant 70% to 80% higher CVD risk. Our observations indicate that the prognostic significance of a smaller versus larger AoR varies in men versus women. Additional studies are warranted to confirm our findings.

scholarly journals Telomere Attrition and Clonal Hematopoiesis of Indeterminate Potential in Cardiovascular Disease

2021 ◽  
Vol 22 (18) ◽  
pp. 9867
Author(s):  
Yi-Chun Huang ◽  
Chao-Yung Wang
Keyword(s):  
Cardiovascular Disease ◽  
Dna Methyltransferase ◽  
Gene Mutations ◽  
Cvd Risk ◽  
Telomere Attrition ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Cell Clones ◽  
Important Relationship ◽  
Increased Risk

Clinical evidence suggests that conventional cardiovascular disease (CVD) risk factors cannot explain all CVD incidences. Recent studies have shown that telomere attrition, clonal hematopoiesis of indeterminate potential (CHIP), and atherosclerosis (telomere–CHIP–atherosclerosis, TCA) evolve to play a crucial role in CVD. Telomere dynamics and telomerase have an important relationship with age-related CVD. Telomere attrition is associated with CHIP. CHIP is commonly observed in elderly patients. It is characterized by an increase in blood cell clones with somatic mutations, resulting in an increased risk of hematological cancer and atherosclerotic CVD. The most common gene mutations are DNA methyltransferase 3 alpha (DNMT3A), Tet methylcytosine dioxygenase 2 (TET2), and additional sex combs-like 1 (ASXL1). Telomeres, CHIP, and atherosclerosis increase chronic inflammation and proinflammatory cytokine expression. Currently, their epidemiology and detailed mechanisms related to the TCA axis remain incompletely understood. In this article, we reviewed recent research results regarding the development of telomeres and CHIP and their relationship with atherosclerotic CVD.

scholarly journals The Glycemic Index, Postprandial Hypotension and Cardiovascular Disease

2021 ◽  
Vol 1 (1) ◽  
Keyword(s):  
Cardiovascular Disease ◽  
Glycemic Index ◽  
Fluid Secretion ◽  
Systemic Circulation ◽  
Cvd Risk ◽  
Postprandial Hypotension ◽  
Increased Risk ◽  
All Cause Mortality ◽  
High Glycemic Index ◽  
Intestinal Fluid Secretion

High glycemic index diets have been associated with an increased risk of cardiovascular disease events and all-cause mortality. We suggest that part of the reason for this association is through the effect of the rapidly digested high glycemic index carbohydrate diets in promoting the effects of postprandial hypotension in vulnerable individuals. Postprandial hypotension has been recognized as a problem especially affecting the frail elderly. The phenomenon occurs earlier in the day and includes syncope and falls acutely and more serious cardiovascular events and increased all-cause mortality in the longer-term. The mechanism appears to relate to the rapid digestion of carbohydrates foods. Strategies that reduce the amount of meal carbohydrates and their rate of absorption by enzyme inhibition or by delaying gastric emptying and have proved helpful as has increased fluid intake, presumably due to dilution of small intestinal contents and a reduction in the tonicity, so reducing the need for intestinal fluid secretion to dilute osmotically active sugars and products of digestion. In this way the need for increased blood flow to the gut can be reduced, that would otherwise steal blood from the systemic circulation resulting in a drop in blood pressure and an increase in heart rate. Slowly absorbed or low glycemic index carbohydrates would therefore appear potentially useful as part of the dietary strategy for the treatment of postprandial hypotension and conversely postprandial hypotension could be one of the reasons why high glycemic index diets have been associated with increased CVD risk.

scholarly journals Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

2019 ◽  
Author(s):  
Daniel B. Rosoff ◽  
George Davey Smith ◽  
Nehal Mehta ◽  
Toni-Kim Clarke ◽  
Falk W. Lohoff
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Alcohol Use ◽  
Tobacco Use ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Cvd Risk ◽  
Increased Risk

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.

Abstract P283: Disparities in Long-term Risk of Cardiovascular Disease by Sexual Orientation and Race/Ethnicity: the National Longitudinal Study of Adolescent Health

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Cari J Clark ◽  
Iris W Borowsky ◽  
Alvaro Alonso ◽  
Rachael A Spencer ◽  
Susan A Everson-Rose
Keyword(s):  
Cardiovascular Disease ◽  
Sexual Orientation ◽  
Longitudinal Study ◽  
Adolescent Health ◽  
Sexual Minorities ◽  
P Value ◽  
Cvd Risk ◽  
National Longitudinal Study ◽  
Increased Risk ◽  
Race Ethnicity

Background: Risk of cardiovascular disease (CVD) may be higher in sexual minorities, but epidemiologic evidence is sparse. We used a nationally representative sample of young adults to examine sex-specific disparities in global CVD risk by sexual orientation and race/ethnicity. Methods: Data were from National Longitudinal Study of Adolescent Health subjects who participated in wave 4 (2008-09) and who had valid weights and non-missing data (7087 women; 6340 men). Age, race/ethnicity, sexual orientation, education, financial stress, and CVD risk factors (body mass index, smoking, diabetes, systolic blood pressure, and use of antihypertensive medication) were collected via an in-home interview. We calculated the 30-Year risk for total CVD using a Framingham-based prediction model. Sex-specific differences in 30-year risk of CVD by sexual orientation were calculated with weighted linear models adjusted for age, race/ethnicity, education, and financial distress. Sex-specific interactions between race/ethnicity and sexual orientation were tested. Results: Mean age was 28.9 ± .2 years; 93% (n=5912) of male participants were heterosexual, 4% (n=258) were bisexual, and 2% (n=170) were gay. 80% (n=5713) of female participants were heterosexual, 18% (n=1243) were bisexual, and 2% (n=131) were lesbian. Average 30-year risk of CVD was 17.2 ± .5% in men and 9.0 ± .3% in women. Differences in CVD risk by sexual orientation were not detectable for men (p=.59). Compared to heterosexual women, bisexual and lesbian women had a .9% (95% CI: .3, 1.4) and 2.0% (95% CI: .7, 3.2) higher risk of CVD, respectively. In race/ethnicity stratified models (interaction p-value=.01), an increased risk among sexual minorities, especially lesbians, was detectable except among Hispanic women (Figure). Conclusion: Disparities in global CVD risk were observed by sexual orientation for women and persisted across most racial/ethnic groups. Sexual orientation may be a marker of increased risk of CVD but more research on contributing factors is needed.

scholarly journals Incidence and risk factors for recurrent cardiovascular disease in middle-eastern adults: a retrospective study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Romona D. Govender ◽  
Saif Al-Shamsi ◽  
Elpidoforos S. Soteriades ◽  
Dybesh Regmi
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Incidence Rate ◽  
United Arab Emirates ◽  
Cox Proportional Hazards ◽  
Cvd Risk ◽  
Female Sex ◽  
Increased Risk ◽  
History Of

Abstract Background Individuals with established cardiovascular disease (CVD) and risk factors such as age, smoking, hypertension, and diabetes mellitus are at an increased risk of recurrent cardiovascular events and death. The incidence rate of recurrent CVD events varies between countries and populations. The United Arab Emirates (UAE) has one of the highest age-standardized death rates for CVD worldwide. The aim of our study was to estimate the incidence rates and determine the predictors of recurrent CVD events among UAE nationals. Methods We investigated an outpatient-based cohort of patients with a history of CVD visiting Tawam Hospital between April 1, 2008 and December 31, 2008. They were followed-up until July 31, 2018. Univariable and multivariable Cox proportional hazards regression models were used to determine the association between major CVD risk factors and the risk of CVD recurrence. Results A total of 216 patients (167 males, 49 females) with a history of CVD were included. They were followed for a median (interquartile range) of 8.1 (5.5–9.3) years, with a total of 1184 patient-years of follow-up. The overall incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. The 8-year cumulative incidence was 73.7%. Age, female sex, and diabetes mellitus were significant predictors of recurrent CVD events, where females had a 1.96 times higher risk of recurrent CVD events than males. Conclusion Significant predictors of recurrent CVD events are older age, female sex, and diabetes mellitus. The incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. Preventive measures, based on international guidelines for CVD management, may improve CVD morbidity and mortality in the UAE population.

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