High homocysteine and low folate plasma concentrations are associated with cardiovascular events but not bleeding during warfarin treatment

AbstractBackground:Previous studies have shown that homocysteine and folate levels in plasma are associated with risk for cardiovascular events and mortality. The aim of this study was to investigate if plasma concentrations of total homocysteine and folate can predict major bleeding, cardiovascular events, and all-cause mortality in patients being treated with warfarin.Methods:In a longitudinal cohort study, 719 patients who were taking warfarin were followed for 3001 treatment years. The following were recorded and classified: major bleeding; cardiovascular events including stroke, arterial emboli, and myocardial infarction (MI); and mortality. Blood samples collected at baseline were analysed for plasma homocysteine and folate levels.Results:After adjustment for age, C-reactive protein, and creatinine, high homocysteine levels were associated with cardiovascular events [hazard ratio (HR) 1.23 per standard deviation (SD); 95% confidence interval (CI): 1.03–1.47], MI (HR 1.38 per SD; 95% CI: 1.03–1.85), and all-cause mortality (HR 1.41 per SD; 95% CI: 1.19–1.68). The highest tertile of folate compared to the lowest tertile was associated with decreased risk for both cardiovascular events (HR 0.64; 95% CI: 0.43–0.91) and MI (HR 0.45; 95% CI: 0.21–0.97). There was no association between major bleeding and homocysteine or folate levels.Conclusions:In patients receiving warfarin treatment, high homocysteine and low folate plasma concentrations are associated with increased risk for cardiovascular events but not major bleeding. For homocysteine levels, there is also an association with all-cause mortality.

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C-Reactive Protein and All-Cause Mortality in a Large Hospital-Based Cohort

Clinical Chemistry ◽

10.1373/clinchem.2007.091959 ◽

2008 ◽

Vol 54 (2) ◽

pp. 343-349 ◽

Cited By ~ 62

Author(s):

Claudia Marsik ◽

Lili Kazemi-Shirazi ◽

Thomas Schickbauer ◽

Stefan Winkler ◽

Christian Joukhadar ◽

...

Keyword(s):

Hospital Admission ◽

Acute Phase ◽

Cox Regression ◽

Disease Risk ◽

C Reactive Protein ◽

Reactive Protein ◽

Increased Risk ◽

All Cause Mortality ◽

Low Sensitivity

Abstract Background: C-reactive protein (CRP), an acute-phase protein, is a sensitive systemic marker of inflammation and acute-phase reactions. Testing CRP concentrations at hospital admission may provide information about disease risk and overall survival. Methods: All first-ever transmittals to the department of medical and chemical laboratory diagnostics for determination of low-sensitivity CRP (n = 274 515, 44.5% male, median age 51 years) between January 1991 and July 2003 were included [median follow-up time: 4.4 years (interquartile range, 2.3–7.4 years)]. The primary endpoint was all-cause mortality. Multivariate Cox regression adjusted for sex and age was applied for analysis. Results: Compared to individuals within the reference category (CRP <5 mg/L), hazard ratios (HR) for all-cause mortality increased from 1.4 (5–10 mg/L category) to 3.3 in the highest category (>80 mg/L, all P <0.001). CRP was associated with various causes of death. The relation of CRP to cancer death was stronger than to vascular death. Younger patients with increased CRP had relatively far worse outcome than older patients (maximal HR: ≤30 years: 6.7 vs >60 years: 1.7–3.7). Interestingly, both short- and long-term mortality were associated with increasing CRP concentrations (>80 mg/L: HR 22.8 vs 1.4). Conclusion: Measurement of low-sensitivity CRP at hospital admission allowed for the identification of patients at increased risk of unfavorable outcome. Our findings indicate that close attention should be paid to hospitalized patients with high CRP not only because of very substantial short-term risk, but also long-term excess risk, the basis for which needs to be determined.

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Antibodies against Malondialdehyde in Haemodialysis Patients and Its Association with Clinical Outcomes: Differences between Subclasses and Isotypes

Journal of Clinical Medicine ◽

10.3390/jcm9030753 ◽

2020 ◽

Vol 9 (3) ◽

pp. 753

Author(s):

Shailesh Kumar Samal ◽

Abdul Rashid Qureshi ◽

Mizanur Rahman ◽

Peter Stenvinkel ◽

Johan Frostegård

Keyword(s):

Significant Risk ◽

Premature Death ◽

C Reactive Protein ◽

Reactive Protein ◽

Multivariate Risk ◽

Increased Risk ◽

All Cause Mortality ◽

Low Levels ◽

Antibody Levels

Patients on haemodialysis (HD-patients) have an increased risk of premature death. Low levels of IgM antibodies against malondialdehyde (anti-MDA) are associated with increased risk of cardiovascular disease (CVD) with underlying potential mechanisms described. Here, we studied subclasses and isotypes of anti-MDA in 210 HD-patients with mortality as outcome (56% men, median age 66, Interquartile range (IQR) 51–74 years, vintage time 29 (15–58) months, mean follow up period of 41 (20–60)months). Patients were also divided into inflamed c-reactive protein (CRP >5.6 mg/mL) and non-inflamed. Antibody levels were measured by ELISA. In multivariate risk analysis, patients in low tertile of IgM anti-MDA sub-distribution hazard ratio (sHR 0.54); 95% confidence interval (CI: 0.34–0.89) inversely and significantly associated with all-cause mortality after five years, after adjusting for confounders. Low tertile of IgG (sHR 0.48, 95%CI: 0.25–0.90, p = 0.02) and IgG1 (sHR 0.50, CI: 0.24–1.04, p = 0.06) was associated low mortality among non-inflamed patients. In contrast, anti-MDA IgG2 among inflamed patients was significantly associated with increased mortality, IgG2(sHR 2.33, CI: 1.16–4.68, p = 0.01). IgM anti-MDA was a novel biomarker among HD-patients with low levels being associated with mortality, while low levels of IgG and IgG1 but not IgA anti-MDA were associated with mortality only among non-inflamed patients. IgG2 anti-MDA was a significant risk marker among inflamed patients, which could be related to infection.

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C-reactive protein for predicting all-cause mortality in patients with acute ischemic stroke: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20181135 ◽

2019 ◽

Vol 39 (2) ◽

Cited By ~ 6

Author(s):

Bo Yu ◽

Ping Yang ◽

Xuebi Xu ◽

Lufei Shao

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Observational Studies ◽

Meta Analysis ◽

C Reactive Protein ◽

Stroke Patients ◽

Reactive Protein ◽

Increased Risk ◽

All Cause Mortality ◽

Unit Increase

Abstract Studies on the association of C-reactive protein (CRP) with all-cause mortality in acute ischemic stroke patients have yielded conflicting results. The objective of this meta-analysis was to evaluate the prognostic value of CRP elevation in predicting all-cause mortality amongst patients with acute ischemic stroke. We searched the original observational studies that evaluated the association of CRP elevation with all-cause mortality in patients with acute ischemic stroke using PubMed and Embase databases until 20 January 2018. Pooled multivariate-adjusted hazard ratio (HR) with 95% confidence intervals (CI) of all-cause mortality was obtained for the highest compared with the lowest CRP level or per unit increment CRP level. A total of 3604 patients with acute ischemic stroke from eight studies were identified. Acute ischemic stroke patients with the highest CRP level were independently associated with an increased risk of all-cause mortality (HR: 2.07; 95% CI: 1.60–2.68) compared with the lowest CRP category. The pooled HR of all-cause mortality was 2.40 (95% CI: 1.10–5.21) for per unit increase in log-transformed CRP. Elevated circulating CRP level is associated with the increased risk of all-cause mortality in acute ischemic stroke patients. This meta-analysis supports the routine use of CRP for the death risk stratification in such patients.

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The High-Sensitivity C-Reactive Protein to Prealbumin Ratio Predicts Adverse Cardiovascular Events after ST-Elevation Myocardial Infarction

The Heart Surgery Forum ◽

10.1532/hsf.3307 ◽

2021 ◽

Vol 24 (1) ◽

pp. E153-E157

Author(s):

Hongqiang Ren ◽

Li Zhao ◽

Yijun Liu ◽

Zhen Tan ◽

Guiquan Luo ◽

...

Keyword(s):

Myocardial Infarction ◽

Roc Curve ◽

Cardiovascular Events ◽

Cox Regression ◽

High Sensitivity ◽

St Elevation Myocardial Infarction ◽

C Reactive Protein ◽

Reactive Protein ◽

Increased Risk ◽

St Elevation

Background: This study evaluated the association of the high-sensitivity C-reactive protein to prealbumin ratio (CPR) with adverse cardiovascular events after ST-elevation myocardial infarction (STEMI) in patients undergoing primary percutaneous coronary intervention (PCI). Methods: The study included 682 patients who presented with STEMI and were treated with primary PCI. Patients were divided into 2 groups: high CPR (CPR ≥0.02) and low CPR (CPR <0.02). The primary endpoint of the study was the occurrence of major adverse cardiovascular events (MACE), defined as cardiovascular mortality or admission due to recurrent AMI or heart failure. Multivariate Cox regression models were used to assess the prognostic value of CPR on MACE in patients with STEMI. Results: During a median follow-up of 18 months, the accumulated incidence rate of MACE was significantly higher in the high-CPR group than in the low-CPR group (38.7% versus 12.0%, P < .01). Multivariate analysis revealed that CPR was an independent predictor for increased risk of MACE (hazard ratio = 3.27, 95% confidence interval [CI] 2.14 to 4.49, P < .01). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve for predicting the diagnosis of MACE was higher for CPR (0.82, 95% CI 0.77 to 0.87) than hs-CRP (0.70, 95% CI 0.65 to 0.75). Conclusion: CPR was independently associated with MACE and can be used for risk stratification in patients with STEMI.

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Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial

European Heart Journal ◽

10.1093/eurheartj/ehaa160 ◽

2020 ◽

Vol 41 (31) ◽

pp. 2952-2961 ◽

Cited By ~ 6

Author(s):

Paul M Ridker ◽

Jean G MacFadyen ◽

Robert J Glynn ◽

Gary Bradwin ◽

Ahmed A Hasan ◽

...

Keyword(s):

Interleukin 6 ◽

Cardiovascular Events ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

C Reactive Protein ◽

Low Density Lipoprotein Cholesterol ◽

Reactive Protein ◽

All Cause Mortality

Abstract Aims In epidemiologic cohorts initiated >30 years ago, inflammatory biomarkers, such as interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were shown to independently predict future cardiovascular events with a magnitude of effect comparable to that of low-density lipoprotein cholesterol (LDLC). Whether aggressive contemporary therapy for atherosclerosis has altered these relationships is unknown yet has major implications for future drug development. Methods and results Interleukin-6, hsCRP, and LDLC were measured at baseline in up to 4168 North American patients enrolled in the contemporary Cardiovascular Inflammation Reduction Trial with prior myocardial infarction or multivessel coronary disease who additionally had diabetes or metabolic syndrome and were followed for a period of up to 5 years for incident major recurrent cardiovascular events and all-cause mortality. Three-quarters of the cohort were previously revascularized and the great majority was taking statins, angiotensin blocking agents, beta-blockers, and antithrombotic agents. Participants were randomly allocated to low-dose methotrexate 15 mg weekly or to placebo. Randomized use of methotrexate had no effect on event rates nor plasma levels of IL-6, hsCRP, or LDL over time. Yet, baseline levels of IL-6, hsCRP, and LDLC were all predictors of major recurrent cardiovascular events; adjusted hazard ratios [HR; 95% confidence interval (CI)] for the lowest to highest baseline quartiles of IL-6 were 1.0 (referent), 1.66 (1.18–2.35), 1.92 (1.36–2.70), and 2.11 (1.49–2.99; P < 0.0001), while adjusted HRs for increasing quartiles of hsCRP were 1.0 (referent), 1.28 (0.92–1.79), 1.73 (1.25–2.38), and 1.79 (1.28–2.50; P < 0.0001) and adjusted HRs for increasing quartiles of LDLC were 1.0 (referent), 1.12 (0.78–1.62), 1.25 (0.87–1.79), and 2.38 (1.72–3.30; P < 0.0001). Effect estimates were not statistically different in these analyses for comparisons between IL-6, hsCRP, or LDLC, although IL-6 was the strongest predictor of all-cause mortality. The highest absolute risks were observed among those with elevated levels of both cholesterol and inflammation [HR 6.4 (95% CI 2.9–14.1) for those in the top quartiles of baseline IL-6 and LDLC, HR 4.9 (95% CI 2.6–9.4) for those in the top quartiles of baseline hsCRP and LDLC, both P < 0.0001]. Conclusion Despite aggressive contemporary secondary prevention efforts, the relationships between inflammation, cholesterol, and cardiovascular risk are largely unchanged from those described two decades ago. These data are consistent with the hypothesis that future treatments for atherosclerosis may require a combination of inflammation inhibition and additional cholesterol reduction. Clinical trial ClinicalTrials.gov NCT01594333.

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Plasma concentrations of C-reactive protein and total homocysteine in relation to the severity and risk factors for cerebrovascular disease

Translational Research ◽

10.1016/j.trsl.2007.02.006 ◽

2007 ◽

Vol 150 (3) ◽

pp. 158-163 ◽

Cited By ~ 22

Author(s):

Maged Y.Z. Youssef ◽

Olusegun A. Mojiminiyi ◽

Nabila A. Abdella

Keyword(s):

Risk Factors ◽

Cerebrovascular Disease ◽

Plasma Concentrations ◽

C Reactive Protein ◽

Reactive Protein ◽

Total Homocysteine

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Comparison of Midregional Pro–A-Type Natriuretic Peptide and the N-Terminal Pro–B-Type Natriuretic Peptide for Predicting Mortality and Cardiovascular Events

Clinical Chemistry ◽

10.1373/clinchem.2011.166348 ◽

2012 ◽

Vol 58 (1) ◽

pp. 293-297 ◽

Cited By ~ 19

Author(s):

Kornelis J J van Hateren ◽

Alaa Alkhalaf ◽

Nanne Kleefstra ◽

Klaas H Groenier ◽

Paul E de Jong ◽

...

Keyword(s):

Natriuretic Peptide ◽

Natriuretic Peptides ◽

Cardiovascular Mortality ◽

Cardiovascular Events ◽

Plasma Concentrations ◽

Population Based ◽

End Points ◽

C Statistic ◽

Increased Risk ◽

All Cause Mortality

Abstract BACKGROUND N-terminal pro–B-type natriuretic peptide (NT-proBNP) provides prognostic information on mortality and future cardiovascular events for individuals from the general population. A novel immunoassay was recently developed that measures a midregional fragment of pro–A-type natriuretic peptide (MR-proANP). We compared the capabilities of MR-proANP and NT-proBNP for predicting mortality and cardiovascular events in a population-based study. METHODS A total of 7819 patients participated in the population-based Prevention of Renal and Vascular End-stage Disease (PREVEND) study, a prospective observational study. Three clinical end points were studied: all-cause mortality, cardiovascular mortality, and cardiovascular events. After a median follow-up of 10.5 years, we used a Cox proportional hazards model to investigate the relationship between the 2 natriuretic peptides and the clinical end points. The Harrell C statistic and the integrated discrimination improvement (IDI) were used to compare MR-proANP and NT-proBNP. RESULTS Increased plasma concentrations of both natriuretic peptides were associated with an increased risk of all-cause mortality and cardiovascular events, after adjustment for age, sex, and other cardiovascular risk factors. According to the Harrell C statistic analysis, the models with MR-proANP and NT-proBNP were comparable in predicting all-cause mortality, cardiovascular mortality, and cardiovascular events. In contrast to NT-proBNP, MR-proANP was not independently related to cardiovascular mortality. In all models, the IDI was higher for NT-proBNP than for MR-proANP. CONCLUSIONS MR-proANP was as efficient as NT-proBNP in predicting all-cause mortality, cardiovascular mortality, and cardiovascular events; however, its association with cardiovascular mortality was not independent from other confounders.

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Association of Very Highly Elevated C-Reactive Protein Concentration with Cardiovascular Events and All-Cause Mortality

Yearbook of Pathology and Laboratory Medicine ◽

10.1016/s1077-9108(10)79475-5 ◽

2011 ◽

Vol 2011 ◽

pp. 260-262

Author(s):

M.G. Bissell

Keyword(s):

Cardiovascular Events ◽

Protein Concentration ◽

C Reactive Protein ◽

Reactive Protein ◽

All Cause Mortality

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Associations between C-reactive protein and all-cause mortality among oldest old adults in Chinese longevity areas: A community-based cohort study

10.21203/rs.2.11072/v1 ◽

2019 ◽

Author(s):

Pei-Liang Chen ◽

Hai-Lian Yang ◽

Zhao-Jin Cao ◽

Xin Cheng ◽

Feng Zhao ◽

...

Keyword(s):

Cohort Study ◽

Smoking Status ◽

Oldest Old ◽

Cox Proportional Hazards ◽

C Reactive Protein ◽

Community Based ◽

Old Adults ◽

Reactive Protein ◽

Increased Risk ◽

All Cause Mortality

Abstract Background: Higher C-reactive protein (CRP) levels have been proposed as a predictor of all-cause mortality in many existing studies from multiple populations, but the association for the oldest old adults (aged 80 and older) remains unclear. Objective: To examine the association between CRP and all-cause mortality among the oldest old Chinese adults. Design: This is a prospective, community-based longitudinal cohort study with 2206 adults aged 80 years old and older with available CRP test results. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (95% CIs) for all-cause mortality according to CRP quartiles, adjusting for potential confounders. Results: The median age of the participants was 93 years old, and the median CRP concentration was 1.13 mg/L at baseline. During a median follow-up period of 36.7 months, 1106 deaths were verified. After full adjustment for potential confounders, a high CRP concentration was positively associated with an increased risk of all-cause mortality. Compared with the lowest quartile, the fully adjusted HRs of the second, third, and fourth quartiles were 1.17 (95% CI: 0.94, 1.46), 1.28 (95% CI: 1.01, 1.61), and 1.50 (95% CI: 1.20, 1.87), respectively. The association of CRP with all-cause mortality was likely modified by smoking status (P = 0.011). Conclusions: Our study indicated that a high CRP concentration was likely to be a prospective factor predicting death among the oldest old adults. Future studies investigating additional factors of disease and aging processes are needed to obtain a better understanding of the mechanisms.

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