Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials

2005 ◽  
Vol 10 (1_suppl) ◽  
pp. S19-S25 ◽  
Author(s):  
Rainer H Böger
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Cardiovascular Events ◽  
Asymmetric Dimethylarginine ◽  
Total Mortality ◽  
No Production ◽  
Intensive Care Unit Treatment ◽  
Increased Risk ◽  
Diverse Patient Populations

Evidence has accumulated that asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. ADMA inhibits vascular NO production at concentrations found in pathophysiological conditions; it also causes local vasoconstriction when infused intra-arterially. ADMA is increased in the plasma of humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal failure, chronic heart failure, and other clinical conditions. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation or reduced NO metabolite levels. In several prospective and cross-sectional studies, ADMA has evolved as a marker of cardio vascular risk. Moreover, prospective clinical studies have suggested that it may play a role as a novel cardiovascular risk factor. Zoccali and coworkers were the first to show that elevated ADMA is associated with a three-fold increased risk of future severe cardiovascular events and mortality in patients undergoing hemodialysis. Valkonen and coworkers demonstrated in a nested case-control study that elevated ADMA was associated with a four-fold increased risk for acute coronary events in clinically healthy, nonsmoking men. In patients with stable angina pectoris, pre- interventional ADMA indicates the risk of developing restenosis or severe clinical events after coronary intervention. Furthermore, in humans with no underlying cardiovascular disease who are undergoing intensive care unit treatment, ADMA is a marker of the mortality risk. A number of additional prospective clinical trials are currently under way in diverse patient populations, among them individuals with congestive heart failure, cardiac transplantation patients, and patients with pulmonary hypertension. In summary, an increasing number of prospective clinical trials have shown that the association between elevated ADMA levels and major cardiovascular events and total mortality is robust and extends to diverse patient populations. However, we need to define more clearly in the future who will profit from ADMA determination, in order to use this novel risk marker as a more specific diagnostic tool.

Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials

2005 ◽  
Vol 10 (2_suppl) ◽  
pp. S19-S25 ◽  
Author(s):  
Rainer H Böger
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Cardiovascular Risk ◽  
Cardiovascular Events ◽  
Asymmetric Dimethylarginine ◽  
Total Mortality ◽  
No Production ◽  
Increased Risk ◽  
Diverse Patient Populations

Evidence has accumulated that asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. ADMA inhibits vascular NO production at concentrations found in pathophysiological conditions; it also causes local vasoconstriction when infused intra-arterially. ADMA is increased in the plasma of humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal failure, chronic heart failure, and other clinical conditions. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation or reduced NO metabolite levels. In several prospective and cross-sectional studies, ADMA has evolved as a marker of cardiovascular risk. Moreover, prospective clinical studies have suggested that it may play a role as a novel cardiovascular risk factor. Zoccali and coworkers were the first to show that elevated ADMA is associated with a three-fold increased risk of future severe cardiovascular events and mortality in patients undergoing hemodialysis. Valkonen and coworkers demonstrated in a nested case-control study that elevated ADMA was associated with a four-fold increased risk for acute coronary events in clinically healthy, nonsmoking men. In patients with stable angina pectoris, preinterventional ADMA indicates the risk of developing restenosis or severe clinical events after coronary intervention. Furthermore, in humans with no underlying cardiovascular disease who are undergoing intensive care unit treatment, ADMA is a marker of the mortality risk. A number of additional prospective clinical trials are currently under way in diverse patient populations, among them individuals with congestive heart failure, cardiac transplantation patients, and patients with pulmonary hypertension. In summary, an increasing number of prospective clinical trials have shown that the association between elevated ADMA levels and major cardiovascular events and total mortality is robust and extends to diverse patient populations. However, we need to define more clearly in the future who will profit from ADMA determination, in order to use this novel risk marker as a more specific diagnostic tool.

scholarly journals Sibling rank and sibling number in relation to cardiovascular disease and mortality risk: a nationwide cohort study

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e042881
Author(s):  
Peter M Nilsson ◽  
Jan Sundquist ◽  
Kristina Sundquist ◽  
Xinjun Li
Keyword(s):  
Cardiovascular Disease ◽  
Mortality Risk ◽  
Cardiovascular Events ◽  
Rank Order ◽  
Total Mortality ◽  
Favourable Effect ◽  
Adjusted Risk ◽  
Increased Risk ◽  
Coronary Events

BackgroundThe number and rank order of siblings could be of importance for risk of cardiovascular disease and mortality. Previous studies have used only fatal events for risk prediction. We, therefore, aimed to use also non-fatal coronary and cardiovascular events in fully adjusted models.MethodsFrom the Multiple-Generation Register in Sweden, data were used from 1.36 million men and 1.32 million women (born 1932–1960), aged 30–58 years at baseline and with follow-up from 1990 to 2015. Mean age at follow-up was 67 years (range 55–83 years). Fatal and non-fatal events were retrieved from national registers.ResultsCompared with men with no siblings, those with 1–2 siblings had a lower, and those with four or more siblings had a higher adjusted risk of cardiovascular events. Again, compared with men with no siblings, those with more than one sibling had a lower total mortality risk, and those with three or more siblings had an increased risk of coronary events.Correspondingly, compared with women with no siblings those women with three siblings or more had an increased risk of cardiovascular events, and those with two siblings or more had an increased risk of coronary events. Women with one sibling or more were at lower total mortality risk, following full adjustment.ConclusionBeing first born is associated with a favourable effect on non-fatal cardiovascular and coronary events for both men and women. The underlying biological mechanisms for this should be studied in a sociocultural context.

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.

The Impact of Atherosclerotic Cardiovascular Risk on Graft Failure in Deceased-Donor Renal Transplantation

2021 ◽  
pp. 152692482110246
Author(s):  
Grace Hsu ◽  
Tracy M. Sparkes ◽  
Brent N. Reed ◽  
Stormi E. Gale ◽  
Brian E. Crossley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Renal Transplant ◽  
Cardiovascular Events ◽  
Graft Failure ◽  
Deceased Donor ◽  
Low Risk ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease

Introduction: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. Research question: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. Design: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. Results: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; ( P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. Discussion: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.

Galectin-3 predicts cardiovascular events in patients with type-2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Lorenzo-Almoros ◽  
A Pello ◽  
A Acena ◽  
J Martinez-Milla ◽  
N Tarin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Plasma Levels ◽  
Cardiovascular Events ◽  
Primary Outcome ◽  
Funding Source ◽  
Increased Risk ◽  
Galectin 3 ◽  
Secondary Outcomes

Abstract Introduction Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods We followed 964 patients with coronary artery disease (CAD), assessing at baseline galectin-3, monocyte chemoattractant protein-1 (MCP-1) and N-terminal fragment of brain natriuretic peptide (NT-proBNP) plasma levels. Secondary outcomes were acute ischemia and heart failure or death. Primary outcome was the combination of the secondary outcomes. Results Male patients were 75.0% in T2DM and 76.6% in the non-T2DM subgroup (p=0.609). Age was 61.0 (54–72) and 60.0 (51–71) years, respectively (p=0.092). 232 patients had T2DM. Patients with T2DM showed higher MCP-1 [144 (113–195) vs. 133 (105–173) pg/ml, p=0.006] and galectin-3 [8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/ml, p=0.049] levels. Median follow-up was 5.39 years (2.81- 6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients [HR 1.57 (1.07–2.30); p=0.022], along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in non-diabetic patients [HR 1.21 (1.04–1.42); p=0.017 and HR 1.23 (1.05–1.44); p=0.012, respectively], along with male sex and age. Galectin-3 was also the only biomarker that predicted the development of acute ischemic events and heart failure or death in T2DM patients, while in non-diabetics MCP-1 and NT-proBNP, respectively, predicted these events. Conclusion In CAD patients, cardiovascular events are predicted by galectin-3 plasma levels in patients with T2DM, and by MCP-1 and NT-proBNP in those without T2DM. Effect of Gal-3 on the primary endpoint Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Insituto de Salud Carlos III

scholarly journals Incremental changes in QRS duration as predictor for cardiovascular disease: a 21-year follow-up of a randomly selected general population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojing Chen ◽  
Per-Olof Hansson ◽  
Erik Thunström ◽  
Zacharias Mandalenakis ◽  
Kenneth Caidahl ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
General Population ◽  
Cardiovascular Events ◽  
Population Sample ◽  
Cox Regression Analysis ◽  
Major Cardiovascular Events ◽  
Increased Risk ◽  
Qrs Duration ◽  
Group 1

AbstractThe QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50–60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07–2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.

P1818Descending aortic thoracic diameter: a risk marker for major adverse cardiovascular outcomes in women

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O L Rueda Ochoa ◽  
L R Bons ◽  
S Rohde ◽  
K E L Ghoud ◽  
R Budde ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Risk ◽  
Cardiovascular Mortality ◽  
Total Mortality ◽  
Population Based ◽  
Cardiovascular Outcomes ◽  
Increased Risk ◽  
Almost All

Abstract Background Thoracic aortic diameters have been associated with cardiovascular risk factors and atherosclerosis. However, limited evidence regarding the role of thoracic aortic diameters as risk markers for major cardiovascular outcomes among women and men exist. Purpose To evaluate the independent associations between crude and indexed ascending and descending aortic (AA and DA) diameters with major cardiovascular outcomes among women and men and to provide optimal cutoff values associated with increased cardiovascular risk. Methods and results 2178 women and men ≥55 years from the prospective population-based Rotterdam Study underwent multi-detector CT scan of thorax. Crude diameters of the AA and DA were measured and indexed by height, weight, body surface area (BSA) and body mass index (BMI). Incidence of stroke, coronary heart disease (CHD), heart failure (HF), cardiovascular and all-cause mortality were evaluated during 13 years of follow-up. Weight-, BSA-, or BMI-indexed AA diameters showed significant associations with total or cardiovascular mortality in both sexes and height-indexed values showed association with HF in women. Crude AA diameters were associated with stroke in men and HF in women. For DA, crude and almost all indexed diameters showed significant associations with either stroke, HF, cardiovascular or total mortality in women. Only weight-, BSA- and BMI-indexed values were associated with total mortality in men. For crude DA diameter, the risk for stroke increased significantly at the 75th percentile among men while the risks for HF and cardiovascular mortality increased at the 75th and 85th percentiles respectively in women. Conclusions Our study suggests a role for descending thoracic aortic diameter as a marker for increased cardiovascular risk, in particular for stroke, heart failure and cardiovascular mortality among women. The cut points for increased risk for several of cardiovascular outcomes were below the 95th percentile of the distribution of aortic diameters.

Plasma asymmetric dimethylarginine and cardiovascular events in patients with acute decompensated heart failure

2008 ◽  
Vol 152 (1) ◽  
pp. 24-30 ◽  
Author(s):  
Christina Dückelmann ◽  
Friedrich Mittermayer ◽  
Dominik G. Haider ◽  
Johann Altenberger ◽  
Michael Wolzt
Keyword(s):  
Heart Failure ◽  
Cardiovascular Events ◽  
Asymmetric Dimethylarginine ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure

scholarly journals Cardiovascular risk after hospitalisation for unexplained syncope and orthostatic hypotension

Heart ◽  
2017 ◽  
Vol 104 (6) ◽  
pp. 487-493 ◽  
Author(s):  
Ekrem Yasa ◽  
Fabrizio Ricci ◽  
Martin Magnusson ◽  
Richard Sutton ◽  
Sabina Gallina ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Orthostatic Hypotension ◽  
Cardiovascular Events ◽  
Hospital Admissions ◽  
Cox Regression ◽  
All Cause Mortality ◽  
Unexplained Syncope ◽  
The Impact

ObjectiveTo investigate the relationship of hospital admissions due to unexplained syncope and orthostatic hypotension (OH) with subsequent cardiovascular events and mortality.MethodsWe analysed a population-based prospective cohort of 30 528 middle-aged individuals (age 58±8 years; males, 40%). Adjusted Cox regression models were applied to assess the impact of unexplained syncope/OH hospitalisations on cardiovascular events and mortality, excluding subjects with prevalent cardiovascular disease.ResultsAfter a median follow-up of 15±4 years, 524 (1.7%) and 504 (1.7%) participants were hospitalised for syncope or OH, respectively, yielding 1.2 hospital admissions per 1000 person-years for each diagnosis. Syncope hospitalisations increased with age (HR, per 1 year: 1.07, 95% CI 1.05 to 1.09), higher systolic blood pressure (HR, per 10 mm Hg: 1.06, 95% CI 1.01 to 1.12), antihypertensive treatment (HR: 1.26, 95% CI 1.00 to 1.59), use of diuretics (HR: 1.77, 95% CI 1.31 to 2.38) and prevalent cardiovascular disease (HR: 1.59, 95% CI 1.14 to 2.23), whereas OH hospitalisations increased with age (HR: 1.11, 95% CI 1.08 to 1.12) and prevalent diabetes (HR: 1.82, 95% CI 1.23 to 2.70). After exclusion of 1399 patients with prevalent cardiovascular disease, a total of 473/464 patients were hospitalised for unexplained syncope/OH before any cardiovascular event. Hospitalisation for unexplained syncope predicted coronary events (HR: 1.85, 95% CI 1.49 to 2.30), heart failure (HR: 2.24, 95% CI 1.65 to 3.04), atrial fibrillation (HR: 1.84, 95% CI 1.50 to 2.26), aortic valve stenosis (HR: 2.06, 95% CI 1.28 to 3.32), all-cause mortality (HR: 1.22, 95% CI 1.09 to 1.37) and cardiovascular death (HR: 1.72, 95% CI 1.23 to 2.42). OH-hospitalisation predicted stroke (HR: 1.66, 95% CI 1.24 to 2.23), heart failure (HR: 1.78, 95% CI 1.21 to 2.62), atrial fibrillation (HR: 1.89, 95% CI 1.48 to 2.41) and all-cause mortality (HR: 1.14, 95% CI 1.01 to 1.30).ConclusionsPatients discharged with the diagnosis of unexplained syncope or OH show higher incidence of cardiovascular disease and mortality with only partial overlap between these two conditions.

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