Coronary Artery Disease Myocardial Infarction Research Articles

Role of bilirubin in the prognosis of coronary artery disease and its relationship with cardiovascular risk factors: a meta-analysis

BackgroundBilirubin is a heme catabolism product with antioxidant, anti-inflammatory, and anti-apoptotic properties and is implicated in the prognosis of several diseases. This study evaluates the prognostic role of bilirubin in coronary artery disease (CAD) patients.MethodsAfter identifying studies from the literature, meta-analyses were performed to achieve a) overall estimates of serum total bilirubin levels in patients with myocardial infarction (MI), non-MI CAD and healthy individuals; b) odds ratios (OR) of adverse outcomes between higher and lower total bilirubin levels; c) standardized mean difference (SMD) in total bilirubin levels in patients with high vs low CAD severity; and d) correlation between disease severity and total bilirubin. Metaregression analyses were performed to examine the relationship between cardiovascular risk factors and increasing quantiles of total bilirubin levels.ResultsForty-three studies were identified. Pooled serum total bilirubin levels were 0.72 mg/dl [95% confidence interval (CI): 0.60, 0.83] in MI patients; 0.65 mg/dl [95% CI: 0.60, 0.69] in non-MI CAD patients; and 0.66 mg/dl [95% CI: 0.56, 0.75] in healthy individuals. Higher total bilirubin levels were associated with greater odds of adverse outcomes in MI patients (OR: 1.08 [95% CI: 0.99, 1.18]) but lower odds in non-MI CAD patients (OR: 0.80 [95%CI: 0.73, 0.88]). Compared to non-severe cases, total bilirubin levels were higher in patients with severe MI (SMD 0.96 [95% CI: − 0.10, 2.01]; p = 0.074) but were lower in severe non-MI CAD patients (SMD − 0.30 [95%CI: − 0.56, − 0.03]; p = 0.02). Total bilirubin levels correlated positively with MI severity (r = 0.41 [95% CI: 0.24, 0.59]; p < 0.01) but correlated negatively with non-MI CAD severity (r = − 0.17 [95% CI: − 0.48, 0.14]; p = 0.28). Female sex was inversely associated with increasing quantiles of bilirubin (meta-regression coefficient: − 8.164 [− 14.531, − 1.769]; p = 0.016) in MI patients.ConclusionPrognostic role of bilirubin for CAD appears complicated, as different odds are observed for MI and non-MI CAD patients which weakens the case of causal involvement of bilirubin in CAD etiology or prognosis.

The change of LDL-C and treatment patterns among documented CAD/MI patients who underwent CAG in Taiwan: A retrospective cohort study

Background and Aims : Limited studies using electronic medical records describe LDL-C goal attainment after coronary artery disease/myocardial infarction (CAD/MI). We aimed to describe changes in LDL-C and treatment patterns after a documented CAD/MI by coronary angiography (CAG) in a medical center in Taiwan.

Segmental speckle tracking strain and strain rate in stable coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Northern Norway Regional Health Authority Background It is known that patients with coronary artery disease (CAD) display reduced global and regional strain and strain rate (SR). However, knowledge about segmental strain and SR in stable CAD patients is still limited. Purpose The purpose of this study was to explore whether segmental strain and SR analyses are different between patients with normal and stenotic coronary arteries among individuals with chest-pain. Methods A total of 510 patients with chest pain, referred to coronary computed tomography angiography (CCTA) and additional 102 patients with myocardial infarction (MI) were prospectively included. All patients underwent transthoracic echocardiography (TTE) with strain-rate analysis. All patients with CCTA-suspected CAD subsequently underwent invasive CAG, as well as in all MI patients. Global longitudinal strain (GLS) and average for segmental peak longitudinal strain during systole (PLS), peak systolic strain rate (PLSR S), peak early diastolic strain rate (PLSR E), post systolic shortening (PSS) measurements were analysed. Further, different cut-off values for reduced strain and SR were used to define the percentage of functionally reduced segments between patients with normal CAD (no CAD), MI, and stable CAD patients who were further treated by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). Results As shown in the table 1, all average segmental strain and SR parameters differed significantly between no CAD and MI groups. However, only PLSR E showed significant differences between no CAD and PCI groups . PLSR E, PLS and GLS showed significant differences between no CAD and CABG groups. The percentage of reduced segmental strain and SR showed similar results. Regarding the percentage of pathological segments at different cut-off values, PLSR E showed the most significant difference between these four groups at a cut-off value 1.5 (p &amp;lt; 0.001) (Figure 1). Conclusion Patients with MI or CABG display clearly reduced segmental strain and SR values. However, in patients with chest-pain, segmental PLSR E seemed to be the only indicator revealing subtle differences between patients with no CAD or those assigned to PCI. The diagnostic value of PLSR E needs to be investigated in further studies. Abstract Table 1 Abstract Figure 1

Identification of Biomarkers Related to Immune Cell Infiltration with Gene Coexpression Network in Myocardial Infarction.

Background There is evidence that the immune system plays a key critical role in the pathogenesis of myocardial infarction (MI). However, the exact mechanisms associated with immunity have not been systematically uncovered. Methods This study used the weighted gene coexpression network analysis (WGCNA) and the CIBERSORT algorithm to analyze the MI expression data from the Gene Expression Omnibus database and then identify the module associated with immune cell infiltration. In addition, we built the coexpression network and protein-protein interactions network analysis to identify the hub genes. Furthermore, the relationship between hub genes and NK cell resting was validated by using another dataset GSE123342. Finally, receiver operating characteristic (ROC) curve analyses were used to assess the diagnostic value of verified hub genes. Results Monocytes and neutrophils were markedly increased, and T cell CD8, T cell CD4 naive, T cell CD4 memory resting, and NK cell resting were significantly decreased in MI groups compared with stable coronary artery disease (CAD) groups. The WGCNA results showed that the pink model had the highest correlation with the NK cell resting infiltration level. We identified 11 hub genes whose expression correlated to the NK cell resting infiltration level, among which, 7 hub genes (NKG7, TBX21, PRF1, CD247, KLRD1, FASLG, and EOMES) were successfully validated in GSE123342. And these 7 genes had diagnostic value to distinguish MI and stable CAD. Conclusions NKG7, TBX21, PRF1, CD247, KLRD1, FASLG, and EOMES may be a diagnostic biomarker and therapeutic target associated with NK cell resting infiltration in MI.

Changes in mortality rates from acute types of coronary artery disease in Russia for the period from 2015 to 2019

Aim. To identify regional specifics of changes in mortality rates from acute types of coronary artery disease (CAD) in 82 Russian regions for the period from 2015 to 2019.Material and methods. The study used data from the Federal State Statistics Service of Russia on mortality from acute CAD types in 82 Russian regions. Standardized death rates (SDRs) for 2015 and 2019 were estimated based on the European standard. We analyzed the SDRs of the population from acute (primary) and recurrent myocardial infarction (MI), other acute CAD types (I21-I22, I24.8 in the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10)).Results. Over the period from 2015 to 2019, mortality from all acute CAD types decreased by 21%, from acute MI — by 9%, from recurrent MI — by 22%, from any MI (acute/recurrent) recurrent — by 14%, and from other CAD types — by 21%. A decrease in mortality from all acute CAD types was recorded in 69 regions, from acute MI — in 58 regions, and recurrent MI — in 62 regions. However, a simultaneous decrease in SDRs from each of the acute CAD types (acute MI, recurrent MI and other acute CAD types) for the period 2015-2019 occurred only in 29 Russian regions. An increase in mortality from all acute CAD types was noted in 14 regions and from any MI — in 21 regions. The coefficient of variation (Cv) for recurrent MI and other acute CAD types of 69% and 103%, respectively, in 2015 and its growth (up to 75% and 134%, respectively) by 2019 indicate growing problems with the coding of death causes.Conclusion. In 2019, compared to 2015, a decrease in mortality from acute CAD types was recorded in most Russian regions. The identified regional specifics require clarification of approaches to death cause coding and the introduction of additions to mortality reduction programs, taking into account the specifics of each Russian region.

Risk factors for Turkish Cypriot patients with coronary artery disease.

IntroductionIschemic heart disease is the leading cause of death worldwide. In this study, we evaluated the risk factors for Turkish Cypriot ischemic heart disease patients.Material and methodsIn this study we examined 7017 patients, retrospectively. 5.9% of the patients had myocardial infarction coronary artery disease (MICAD) and 94.1% of the patients were control patients. The mean age of the study population was 52, and 39.2% were female. The risk factors considered were: age, sex, hypertension (HT), diabetes mellitus (DM), family history of coronary artery disease, smoking, high total cholesterol levels and obesity.ResultsConsistently with the presumed risk factors, there was a significant difference between MICAD and control groups in our study for smoking, HT, DM and obesity. However, our study revealed no significant difference for high total cholesterol levels in contrast to the current literature. Assessing the risk factors among male and female patient groups separately, both men and women have the highest risk prevalence for hypertension. Smoking is the second most common risk factor among males, whereas it is the family history of coronary heart disease in the female group. HT, DM and obesity were found to be significant risk factors for both males and females in our study group, while family history was revealed to be significant only in women.ConclusionsModifiable risk factors such as smoking, hypertension, diabetes mellitus and obesity may be controlled by lifestyle changes and medical therapies, and should be approached with caution for preventing cardiac events. Non-modifiable risk factors such as age, gender, family history and ethnicity should be taken into account for disease prediction.

Outcome of acute myocardial infarction versus stable coronary artery disease patients treated with coronary bypass surgery

Objective To study the long-term outcome differences between acute myocardial infarction (MI) and stable coronary artery disease (CAD) patients treated with coronary artery bypass grafting (CABG). Methods We studied retrospectively patients with MI (n = 1882) or stable CAD (n = 13117) treated with isolated CABG between 2004 and 2014. Inverse propensity probability weight adjustment for baseline features was used. Median follow-up was 7.9 years. Results In-hospital mortality (8.6% vs. 1.6%; OR 5.94; p < .0001) and re-sternotomy (5.5% vs. 2.7%; OR 2.07; p < .0001) were more common in MI patients compared to stable CAD patients. Hospital surviving MI patients had higher all-cause mortality (28.2% vs. 22.2%; HR 1.37; p = .002) and MACE rate (34.4% vs. 27.4%; HR 1.22; CI 1.00–1.50; p = .049) at 10-year follow-up. Cardiovascular mortality (15.9% vs. 12.7%; HR 1.36; p = .017) and rate of new myocardial infarction (12.0% vs. 9.8%; HR 1.40; p = .034) were also higher in MI patients during follow-up. In follow-up of stabilized first-year survivors, the difference in all-cause (26.5% vs. 20.7%; HR 1.40; p = .003) and cardiovascular (14.2% vs. 11.4%; HR 1.37; p = .027) mortality continued to increase between MI and stable CAD patients. Conclusion MI patients have poorer short- and long-term outcomes compared to stable CAD patients after CABG and risk difference continues to increase with time. Key Messages Patients with myocardial infarction have poorer short- and long-term outcomes compared to stable coronary artery disease patients after coronary artery bypass grafting (CABG). Higher risk of death continues also in stabilized first-year myocardial infarct survivors. The importance of efficient secondary prevention and follow-up highlights in post-myocardial infarct population after CABG.

Pericoronary adipose tissue computed tomography attenuation distinguishes different stages of coronary artery disease: a cross-sectional study.

Vascular inflammation inhibits local adipogenesis in pericoronary adipose tissue (PCAT) and this can be detected on coronary computed tomography angiography (CCTA) as an increase in CT attenuation of PCAT surrounding the proximal right coronary artery (RCA). In this cross-sectional study, we assessed the utility of PCAT CT attenuation as an imaging biomarker of coronary inflammation in distinguishing different stages of coronary artery disease (CAD). Sixty patients with acute myocardial infarction (MI) were prospectively recruited to undergo CCTA within 48 h of admission, prior to invasive angiography. These participants were matched to patients with stable CAD (n = 60) and controls with no CAD (n = 60) by age, gender, BMI, risk factors, medications, and CT tube voltage. PCAT attenuation around the proximal RCA was quantified per-patient using semi-automated software. Patients with MI had a higher PCAT attenuation (-82.3 ± 5.5 HU) compared with patients with stable CAD (-90.6 ± 5.7 HU, P < 0.001) and controls (-95.8 ± 6.2 HU, P < 0.001). PCAT attenuation was significantly increased in stable CAD patients over controls (P = 0.01). The association of PCAT attenuation with stage of CAD was independent of age, gender, cardiovascular risk factors, epicardial adipose tissue volume, and CCTA-derived quantitative plaque burden. No interaction was observed for clinical presentation (MI vs. stable CAD) and plaque burden on PCAT attenuation. PCAT CT attenuation as a quantitative measure of global coronary inflammation independently distinguishes patients with MI vs. stable CAD vs. no CAD. Future studies should assess whether this imaging biomarker can track patient responses to therapies in different stages of CAD.

Myocardial Infarction Associates With a Distinct Pericoronary Adipose Tissue Radiomic Phenotype: A Prospective Case-Control Study

ObjectivesThis study sought to determine whether coronary computed tomography angiography (CCTA)-based radiomic analysis of pericoronary adipose tissue (PCAT) could distinguish patients with acute myocardial infarction (MI) from patients with stable or no coronary artery disease (CAD). BackgroundImaging of PCAT with CCTA enables detection of coronary inflammation. Radiomics involves extracting quantitative features from medical images to create big data and identify novel imaging biomarkers. MethodsIn a prospective case-control study, 60 patients with acute MI underwent CCTA within 48 h of admission, before invasive angiography. These subjects were matched to patients with stable CAD (n = 60) and controls with no CAD (n = 60) by age, sex, risk factors, medications, and CT tube voltage. PCAT was segmented around the proximal right coronary artery (RCA) in all patients and around culprit and nonculprit lesions in patients with MI. PCAT segmentations were analyzed using Radiomics Image Analysis software. ResultsOf 1,103 calculated radiomic parameters, 20.3% differed significantly between MI patients and controls, and 16.5% differed between patients with MI and stable CAD (critical p < 0.0006); whereas none differed between patients with stable CAD and controls. On cluster analysis, the most significant radiomic parameters were texture or geometry based. At 6 months post-MI, there was no significant change in the PCAT radiomic profile around the proximal RCA or nonculprit lesions. Using machine learning (XGBoost), a model integrating clinical features (risk factors, serum lipids, high-sensitivity C-reactive protein), PCAT attenuation, and radiomic parameters provided superior discrimination of acute MI (area under the receiver operator characteristic curve [AUC]: 0.87) compared with a model with clinical features and PCAT attenuation (AUC: 0.77; p = 0.001) or clinical features alone (AUC: 0.76; p < 0.001). ConclusionsPatients with acute MI have a distinct PCAT radiomic phenotype compared with patients with stable or no CAD. Using machine learning, a radiomics-based model outperforms a PCAT attenuation-based model in accurately identifying patients with MI.

Clinical features, sex differences and outcomes of myocardial infarction with nonobstructive coronary arteries: a registry analysis.

Clinical characteristics and outcomes of patients diagnosed with myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) remain largely unknown. Furthermore, we do not yet understand if women with MINOCA have worse outcomes similar to what has historically been observed with MI. The aims of the current study were to evaluate the (1) incidence of MINOCA in patients presenting with MI, (2) compare in-hospital outcomes of MINOCA and obstructive atherosclerotic coronary artery disease MI (OACD-MI), and (3) comparison of in-hospital clinical outcomes of patients with MINOCA stratified by sex. In this observational study, we combined data from two large university hospitals from Canada and Australia. Clinical characteristics and in-hospital outcomes of MINOCA and OACD-MI were analyzed by matching these patients in a 1:1 ratio after selecting patients with OACD-MI by systematic random sampling. Clinical characteristics associated with MINOCA were identified through multivariate logistic regression. Primary outcome of interest was net adverse cardiovascular events (NACE) defined as death, heart failure, stroke, and major bleeding. The incidence rate of MINOCA was 9.5%. Women, absence of traditional cardiac risk factors, and absence of ST-deviations on ECG were associated with diagnosis of MINOCA on angiography. NACE (P = 0.0001), death (P = 0.019), stroke (P = 0.002), and heart failure (P = 0.001) were significantly lower in patients with MINOCA. Subgroup analysis of women and men diagnosed with MINOCA revealed similar in-hospital outcomes. The incidence of MINOCA was 9.5%. Compared to OACD-MI, patients with MINOCA have less cardiac risk factors. In-hospital outcomes of patients diagnosed with MINOCA were better than OACD-MI.

Cardio-Renal Biomarker Soluble Urokinase-Type Plasminogen Activator Receptor Is Associated With Cardiovascular Death and Myocardial Infarction in Patients With Coronary Artery Disease Independent of Troponin, C-Reactive Protein, and Renal Function.

BackgroundRisk stratification among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Thus, we evaluated the predictive value of soluble urokinase‐type plasminogen activator receptor (suPAR) levels for cardiovascular mortality and nonfatal myocardial infarction in patients with CAD.Methods and ResultsPlasma levels of suPAR were measured in a cohort of 1703 patients with documented CAD as evidenced by coronary angiography—including 626 patients with acute coronary syndrome and 1077 patients with stable angina pectoris. Cardiovascular death and/or nonfatal myocardial infarction were defined as main outcome measures. During a median follow‐up of 3.5 years, suPAR levels reliably predicted cardiovascular death or myocardial infarction in CAD, evidenced by survival curves stratified for tertiles of suPAR levels. In Cox regression analyses, the hazard ratio for the prediction of cardiovascular death and/or myocardial infarction was 2.19 (P<0.001) in the overall cohort and 2.56 in the acute coronary syndrome cohort (P<0.001). Even after adjustment for common cardiovascular risk factors, renal function and the biomarkers C‐reactive protein, N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity troponin I suPAR still enabled a reliable prediction of cardiovascular death or myocardial infarction with a hazard ratio of 1.61 (P=0.022) in the overall cohort and 2.22 (P=0.005) in the acute coronary syndrome cohort.ConclusionsSuPAR has a strong and independent prognostic value in secondary prevention settings, and thereby might represent a valuable biomarker for risk estimation in CAD.

Change in matrix metalloproteinase 2, 3, and 9 levels at the time of and after acute atherothrombotic myocardial infarction.

Elevated measures of matrix metalloproteinases (MMPs) are associated with acute myocardial infarction (MI), but it is not known how long these changes persist post-MI or if these measures differ between atherothrombotic versus non-atherothrombotic MI. MMPs-2, 3, and 9 were measured in 80 subjects with acute MI (atherothrombotic and non-atherothrombotic MI) or stable coronary artery disease (CAD). Measurements were made at, the time of acute MI, and > 3-month following acute MI (quiescent phase). Outcome measures were compared between groups and between time of acute MI and quiescent post-MI follow-up using Wilcoxon's and repeated measures analysis of variance. Forty-nine subjects met the criteria for acute MI with clearly defined atherothrombotic (n = 22) and non-atherothrombotic (n = 12) subsets. Fifteen subjects met criteria for stable CAD. MMP-3 was higher in acute MI versus stable CAD subjects at the time of acute MI: (453 vs. 217pg/mL, p = 0.010) but not at quiescent phase follow-up (p > 0.05). MMP-9 was higher in acute MI versus stable CAD subjects at the time of acute MI: (412 vs. 168pg/mL, p = 0.002) but not at the quiescent phase follow-up (p > 0.05). MMP-9 was higher at the time of acute MI versus quiescent phase follow-up in acute MI (412 vs. 213pg/mL, p = 0.001) and atherothrombotic MI specifically (458 vs. 212pg/mL, p = 0.001). No difference in MMP-2, 3, or 9 was observed between atherothrombotic versus non-atherothrombotic MI subgroups. MMPs-3 and 9 are significantly elevated in acute MI verses stable CAD subjects at time of acute MI but not different at quiescent phase follow-up. MMP-9 is elevated at the time of acute MI and specifically in acute atherothrombotic MI at time of MI versus quiescent phase follow-up.

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

BackgroundMetformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD).MethodsRelevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL).ResultsIn this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don’t use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = − 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = − 0.02) and LDL (MD = − 0.08).ConclusionMetformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.

Unsatisfactory risk factor control and high rate of new cardiovascular events in patients with myocardial infarction and prior coronary artery disease

BackgroundPatients with established coronary artery disease (CAD) have an increased risk of new cardiovascular events. An underuse of secondary preventive drugs has been observed, and many patients may not attain the treatment goals for secondary prevention. The aims of the present nationwide register-based cohort study were to assess the degree of risk factor control and long-term outcomes in patients < 80 years with Type 1 myocardial infarction (MI) with and without prior CAD.MethodsData concerning all patients with MI admitted to hospitals in Norway from 2013 to 2016 were retrieved from the Norwegian Myocardial Infarction Register (NORMI). Long-term mortality was obtained through linkage with the Norwegian Cause of Death Registry.ResultsIn total, 47,204 patients were registered in the NORMI from 2013 to 2016. Prior CAD was recorded in 7219 (25.2%) of the 28,607 patients < 80 years old with Type 1 MIs. On average, 3 of the 6 defined treatment targets for secondary preventive therapy were attained, and only 1% of the patients achieved all targets. Patients with MI and prior CAD had increased risk of death or new MI compared to patients without prior CAD during long-term follow-up (adjusted HR 1.6, 95% CI 1.5–1.7).ConclusionsPrior CAD was frequent in patients with acute MI. The attainment of secondary preventive treatment targets in patients with MI and prior CAD was not optimal, and the long-term outcomes were reduced compared to patients without prior CAD. Increased efforts to improve risk factor control are needed.

Roles of the Chr.9p21.3 ANRIL Locus in Regulating Inflammation and Implications for Anti-Inflammatory Drug Target Identification.

Periodontitis (PD) is a common gingival infectious disease caused by an over-aggressive inflammatory reaction to dysbiosis of the oral microbiome. The disease induces a profound systemic inflammatory host response, that triggers endothelial dysfunction and pro-thrombosis and thus may aggravate atherosclerotic vascular disease and its clinical complications. Recently, a risk haplotype at the ANRIL/CDKN2B-AS1 locus on chromosome 9p21.3, that is not only associated with coronary artery disease / myocardial infarction (CAD/MI) but also with PD, could be identified by genome-wide association studies. The locus encodes ANRIL - a long non-coding RNA (lncRNA) which, like other lncRNAs, regulates genome methylation via interacting with specific DNA sequences and proteins, such as DNA methyltranferases and polycomb proteins, thereby affecting expression of multiple genes by cis and trans mechanisms. Here, we describe ANRIL regulated genes and metabolic pathways and discuss implications of the findings for target identification of drugs with potentially anti-inflammatory activity in general.

Circulating Prolidase Activity in Patients with Myocardial Infarction.

Collagen is a major determinant of atherosclerotic plaque stability. Thus, identification of differences in enzymes that regulate collagen integrity could be useful for predicting susceptibility to atherothrombosis or for diagnosing plaque rupture. In this study, we sought to determine whether prolidase, the rate-limiting enzyme of collagen turnover, differs in human subjects with acute myocardial infarction (MI) versus those with stable coronary artery disease (CAD). We measured serum prolidase activity in 15 patients with stable CAD and 49 patients with acute MI, of which a subset had clearly defined thrombotic MI (n = 22) or non-thrombotic MI (n = 12). Prolidase activity was compared across study time points (at cardiac catheterization, T0; 6 h after presentation, T6; and at a quiescent follow-up, Tf/u) in acute MI and stable CAD subjects. We performed subgroup analyses to evaluate prolidase activity in subjects presenting with acute thrombotic versus non-thrombotic MI. Although prolidase activity was lower at T0 and T6 versus the quiescent phase in acute MI and stable CAD subjects (p < 0.0001), it was not significantly different between acute MI and stable CAD subjects at any time point (T0, T6, and Tf/u) or between thrombotic and non-thrombotic MI groups. Preliminary data from stratified analyses of a small number of diabetic subjects (n = 8) suggested lower prolidase activity in diabetic acute MI subjects compared with non-diabetic acute MI subjects (p = 0.02). Circulating prolidase is not significantly different between patients with acute MI and stable CAD or between patients with thrombotic and non-thrombotic MI. Further studies are required to determine if diabetes significantly affects prolidase activity and how this might relate to the risk of MI.

Effect of handgrip on coronary artery disease and myocardial infarction: a Mendelian randomization study

Observational studies have reported an association of handgrip strength with risk of cardiovascular disease. However, residual confounding and reverse causation may have influenced these findings. A Mendelian randomization (MR) study was conducted to examine whether handgrip is causally associated with cardiovascular disease. Two single nucleotide polymorphisms (SNPs), rs3121278 and rs752045, were used as the genetic instruments for handgrip. The effect of each SNP on coronary artery disease/myocardial infarction (CAD/MI) was weighted by its effect on handgrip strength, and estimates were pooled to provide a summary measure for the effect of increased handgrip on risk of CAD/MI. MR analysis showed that higher grip strength reduces risk for CAD/MI, with 1-kilogram increase in genetically determined handgrip reduced odds of CAD by 6% (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.91–0.99, P = 0.01), and reduced odds of MI by 7% (OR = 0.93, 95% CI 0.89–0.98, P = 0.003). No association of grip strength with type 2 diabetes, body mass index, LDL- and HDL-cholesterol, triglycerides and fasting glucose was found. The inverse causal relationship between handgrip and the risk of CAD or MI suggests that promoting physical activity and resistance training to improve muscle strength may be important for cardiovascular health.

Identification of a plasma metabolomic signature of thrombotic myocardial infarction that is distinct from non-thrombotic myocardial infarction and stable coronary artery disease.

AimsCurrent non-invasive diagnostics for acute myocardial infarction (MI) identify myocardial necrosis rather than the primary cause and therapeutic target—plaque disruption and resultant thrombosis. The aim of this study was to identify changes specific to plaque disruption and pathological thrombosis that are distinct from acute myocardial necrosis.Methods and resultsWe quantified 1,032 plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic MI, and 15 stable coronary artery disease (CAD) subjects at two acute phase (time of catheterization [T0], six hours [T6]) and one quiescent (>3 months follow-up) time points. A statistical classifier was constructed utilizing baseline (T0) abundances of a parsimonious set of 17 qualifying metabolites. Qualifying metabolites were those that demonstrated a significant change between the quiescent phase and the acute phase and that were distinct from any change seen in non-thrombotic MI or stable CAD subjects. Classifier performance as estimated by 10-fold cross-validation was suggestive of high sensitivity and specificity for differentiating thrombotic from non-thrombotic MI and stable CAD subjects at presentation.Nineteen metabolites demonstrated an intra-subject change from time of acute thrombotic MI presentation to the quiescent state that was distinct from any change measured in both the non-thrombotic MI and stable CAD subjects undergoing cardiac catheterization over the same time course (false discovery rate <5%).ConclusionsWe have identified a candidate metabolic signature that differentiates acute thrombotic MI from quiescent state after MI, from acute non-thrombotic MI, and from stable CAD. Further validation of these metabolites is warranted given their potential as diagnostic biomarkers and novel therapeutic targets for the prevention or treatment of acute MI.

Plasma levels of the anti-coagulation protein C and the risk of ischaemic heart disease. A Mendelian randomisation study.

Protein C is an environmentally modifiable anticoagulant, which protects against venous thrombosis, whether it also protects against ischaemic heart disease is unclear, based on observational studies and relatively small genetic studies. It was our study aim to clarify the role of protein C in ischaemic heart disease. The risk of coronary artery disease/myocardial infarction (CAD/MI) was assessed according to genetically predicted protein C in very large studies. Associations with lipids and diabetes were similarly assessed to rule out effects via traditional cardiovascular disease risk factors. Separate sample instrumental variable analysis with genetic instruments (Mendelian randomisation) was used to obtain an unconfounded estimate of the association of protein C (based on (rs867186 (PROCR), rs3746429 (EDEM2), rs7580658 (inter/PROC)) with CAD/MI in an extensively genotyped case (n=64374)-control (n=130681) study, CARDIoGRAMplusC4D. Associations with lipids and diabetes were similarly assessed using the Global Lipids Genetics Consortium Results (n=196,475) and the DIAbetes Genetics Replication And Meta-analysis case (n=34,380)-control (n=114,981) study. Genetically predicted protein C was negatively associated with CAD/MI, odds ratio (OR) 0.85 µg/ml, 95 % confidence interval 0.80 to 0.90, but had no such negative association with lipids or diabetes. Results were similar for the SNP rs867186 functionally relevant to protein C, and including additional potentially pleiotropic SNPs (rs1260326 (GCKR), rs17145713 (BAZ1B) and rs4321325 (CYP27C1)). In conclusion, protein C may protect against CAD/MI. Whether environmental or dietary items that raise protein C protect against ischaemic cardiovascular disease by that mechanism should be investigated.

Platelet Count and Mean Platelet Volume at the Time of and After Acute Myocardial Infarction

Platelet count has been shown to be lower and mean platelet volume (MPV) to be higher in acute myocardial infarction (MI). However, it is not known whether these changes persist post-MI or if these measures are able to distinguish between acute thrombotic and non-thrombotic MI. Platelet count and MPV were measured in 80 subjects with acute MI (thrombotic and non-thrombotic) and stable coronary artery disease (CAD) at cardiac catheterization (acute phase) and at >3-month follow-up (quiescent phase). Subjects were stratified using stringent clinical, biochemical, histological, and angiographic criteria. Outcome measures were compared between groups by analysis of variance. Forty-seven subjects met criteria for acute MI with clearly defined thrombotic (n = 22) and non-thrombotic (n = 12) subsets. Fourteen subjects met criteria for stable CAD. No significant difference was observed in platelet count between subjects with acute MI and stable CAD at the acute or quiescent phase. MPV was higher in acute MI (9.18 ± 1.21) compared to stable CAD (8.13 ± 0.66; P = 0.003) at the acute phase but not at the quiescent phase (8.48 ± 0.58 vs 8.94 ± 1.42; P = 0.19). No difference in platelet count or MPV was detected between thrombotic and non-thrombotic subsets at acute or quiescent phases. The power to detect differences in these measures between thrombotic and non-thrombotic subsets was 58%. Higher MPV at the time of acute MI is not observed by 3 months post-MI (quiescent phase). Platelet count and MPV do not differ in subjects with thrombotic versus non-thrombotic MI. Further investigation is warranted to evaluate the utility of these measures in the diagnosis of acute MI.