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.

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.

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.

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.

Cardiovascular Risk Assessment and Impact of Medications on Cardiovascular Disease in Inflammatory Bowel Disease

2020 ◽  
Author(s):  
Preetika Sinh ◽  
Raymond Cross
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Inflammatory Bowel Disease ◽  
Cardiovascular Risk ◽  
Lupus Erythematosus ◽  
Bowel Disease ◽  
Severe Heart Failure ◽  
Janus Kinase ◽  
Increased Risk ◽  
Inflammatory Bowel

Abstract There is increased risk of cardiovascular disease in patients with chronic inflammatory disorders such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus. Studies have shown association between cardiovascular disease (eg, myocardial infarction, heart failure, stroke) and inflammatory bowel disease. Medications such as infliximab and adalimumab (monoclonal antibodies to tumor necrosis factor α) may help decrease the inflammatory burden and cardiovascular risk; however, there have been reports of hypertriglyceridemia and worsening of moderate to severe heart failure with these medications. Janus kinase inhibitors, such as tofacitinib, have been associated with hyperlipidemia and thromboembolism. We aim to discuss clinical and imaging modalities to assess cardiovascular risk in inflammatory bowel disease patients and review the role of various medications with respect to cardiovascular disease in this population.

scholarly journals Family history and polygenic risk of cardiovascular disease: independent factors associated with secondary cardiovascular events in patients undergoing carotid endarterectomy

2019 ◽  
Author(s):  
Nathalie Timmerman ◽  
Dominique P.V. de Kleijn ◽  
Gert J. de Borst ◽  
Hester M. den Ruijter ◽  
Folkert W. Asselbergs ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Family History ◽  
Carotid Endarterectomy ◽  
Cardiovascular Risk Factors ◽  
Cardiovascular Events ◽  
Polygenic Risk ◽  
Increased Risk ◽  
The Impact

AbstractBackgroundFamily history (FHx) of cardiovascular disease (CVD) is a risk factor for CVD and a proxy for cardiovascular heritability. Polygenic risk scores (PRS) summarizing >1 million variants for coronary artery disease (CAD) are associated with incident and recurrent CAD events. However, little is known about the influence of FHx or PRS on secondary cardiovascular events (sCVE) in patients undergoing carotid endarterectomy (CEA).MethodsWe included 1,788 CEA patients from the Athero-Express Biobank. A weighted PRS for CAD including 1.7 million variants was calculated (MetaGRS). The composite endpoint of sCVE during three years follow-up included coronary, cerebrovascular and peripheral events and cardiovascular death. We assessed the impact of FHx and MetaGRS on sCVE and carotid plaque composition.ResultsPositive FHx was associated with a higher 3-year risk of sCVE independent of cardiovascular risk factors and MetaGRS (adjusted HR 1.40, 95%CI 1.07-1.82, p=0.013). Patients in the highest MetaGRS quintile had a higher 3-year risk of sCVE compared to the rest of the cohort independent of cardiovascular risk factors including FHx (adjusted HR 1.35, 95%CI 1.01-1.79, p=0.043), and their atherosclerotic plaques contained more fat (adjusted OR 1.59, 95%CI, 1.11-2.29, p=0.013) and more macrophages (OR 1.49, 95%CI 1.12-1.99, p=0.006).ConclusionIn CEA patients, both positive FHx and higher MetaGRS were independently associated with increased risk of sCVE. Moreover, higher MetaGRS was associated with vulnerable plaque characteristics. Future studies should unravel underlying mechanisms and focus on the added value of PRS and FHx in individual risk prediction for sCVE.

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.

Tooth Loss Predicts Myocardial Infarction, Heart Failure, Stroke, and Death

2019 ◽  
Vol 98 (2) ◽  
pp. 164-170 ◽  
Author(s):  
H.J. Lee ◽  
E.K. Choi ◽  
J.B. Park ◽  
K.D. Han ◽  
S. Oh
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Risk ◽  
Cardiovascular Events ◽  
Tooth Loss ◽  
Multivariable Analysis ◽  
Missing Teeth ◽  
Increased Risk ◽  
Korean National Health Insurance

We investigated whether oral health, represented by missing teeth, was associated with an increased risk of cardiovascular disease, including myocardial infarction (MI), heart failure (HF), stroke, and all-cause mortality. Subjects who underwent routine dental examinations and health checkups provided by the Korean National Health Insurance from 2007 to 2008 ( n = 4,440,970) were followed up for incident MI, HF, stroke, and death until 2016. During follow-up of 7.56 y, 68,063 (1.5%) subjects died, and 31,868 (0.7%) were admitted for MI, 22,637 (0.5%) for HF, and 30,941 (0.7%) for stroke. Cardiovascular events and mortality increased in proportion to tooth loss. Tooth loss was an independent risk factor for cardiovascular events after multivariable analysis adjusted for cardiovascular risk, behavioral, and income factors. Each missing tooth was associated with an approximately 1% increase in MI (HR, 1.010; 95% CI, 1.007 to 1.014), 1.5% increase in HF (HR, 1.016; 95% CI, 1.013 to 1.019) and stroke (HR, 1.015; 95% CI, 1.012 to 1.018), and 2% increase in mortality (HR, 1.022; 95% CI, 1.020 to 1.023). Having ≥5 missing teeth substantially increased risk for cardiovascular outcomes, and even a small number of missing teeth (1 to 4) was associated with an increased risk for MI, stroke, and death. This association was consistent in subgroup analyses and especially strong among the younger subjects (age <65 y) and those with periodontitis. In this large Korean nationwide cohort study, we found that tooth loss showed a dose-dependent association with incident MI, HF, ischemic stroke, and all-cause death and was a good predictor of cardiovascular outcome. In clinical practice, the number of missing teeth can aid physicians in discriminating patients with a higher cardiovascular risk.

scholarly journals Journal Watch

2011 ◽  
Vol 10 (3) ◽  
pp. 150-152
Author(s):  
Mohammed Zahid
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Events ◽  
Excess Mortality ◽  
Increased Risk ◽  
Journal Watch ◽  
Onset Atrial Fibrillation ◽  
New Onset

The aim of this study was to look at the association between new onset atrial fibrillation (AF) and mortality as well as the influence of cardiovascular co-morbidities on risk in middle-aged women without cardiovascular disease at baseline. This large study demonstrated that those women who developed AF had an increased risk of all-cause, cardiovascular, and non-cardiovascular mortality compared with women who did not develop AF. Excess mortality associated with AF appears attributable to the occurrence of nonfatal cardiovascular events prior to death. It would seem that cardiovascular risk factors should be managed aggressively in patients with AF to try to reduce these deaths. Conen D, et al. JAMA 2011 May 25; 2080 – 87

scholarly journals Prediction of Cardiovascular Events by Type I Central Systolic Blood Pressure

Hypertension ◽  
2020 ◽  
Author(s):  
Florence Lamarche ◽  
Mohsen Agharazii ◽  
François Madore ◽  
Rémi Goupil
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Events ◽  
Administrative Databases ◽  
Youden Index ◽  
Major Adverse Cardiovascular Events ◽  
Type I ◽  
Increased Risk

Compared with brachial blood pressure (BP), central systolic BP (SBP) can provide a better indication of the hemodynamic strain inflicted on target organs, but it is unclear whether this translates into improved cardiovascular risk stratification. We aimed to assess which of central or brachial BP best predicts cardiovascular risk and to identify the central SBP threshold associated with increased risk of future cardiovascular events. This study included 13 461 participants of CARTaGENE with available central BP and follow-up data from administrative databases but without cardiovascular disease or antihypertensive medication. Central BP was estimated by radial artery tonometry, calibrated for brachial SBP and diastolic BP (type I), and a generalized transfer function (SphygmoCor). The outcome was major adverse cardiovascular events. Cox proportional-hazards models, differences in areas under the curves, net reclassification indices, and integrated discrimination indices were calculated. Youden index was used to identify SBP thresholds. Over a median follow-up of 8.75 years, 1327 major adverse cardiovascular events occurred. The differences in areas under the curves, net reclassification indices, and integrated discrimination indices were of 0.2% ([95% CI, 0.1–0.3] P <0.01), 0.11 ([95% CI, 0.03–0.20] P =0.01), and 0.0004 ([95% CI, −0.0001 to 0.0014] P =0.3), all likely not clinically significant. Central and brachial SBPs of 112 mm Hg (95% CI, 111.2–114.1) and 121 mm Hg (95% CI, 120.2–121.9) were identified as optimal BP thresholds. In conclusion, central BP measured with a type I device is statistically but likely not clinically superior to brachial BP in a general population without prior cardiovascular disease. Based on the risk of major adverse cardiovascular events, the optimal type I central SBP appears to be 112 mm Hg.

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