Serum Levels of Dihomo-Gamma (γ)-Linolenic Acid (DGLA) Are Inversely Associated with Linoleic Acid and Total Death in Elderly Patients with a Recent Myocardial Infarction

Dihomo-gamma-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid (PUFA) derived from linoleic acid (LA). The LA:DGLA ratio reflects conversion from LA to DGLA. Low levels of DGLA in serum have been related to poor outcome in myocardial infarction (MI) patients. Aims: To assess the association of DGLA and LA:DGLA with total death as a primary aim and incident cardiovascular events as a secondary objective. Methods: Baseline samples from 1002 patients, aged 70 to 82 years, included 2–8 weeks after an MI and followed for 2 years, were used. Major adverse clinical events (MACE) consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. Cox regression analysis was used to relate serum n-6 PUFA phospholipid levels (%wt) to the risk of MACE, adjusting for the following: (1) age, sex and body mass index (BMI); (2) adding baseline cod liver oil supplementation; (3) adding prevalent hypertension, chronic kidney disease and diabetes mellitus. Results: Median DGLA level in serum phospholipids was 2.89 (Q1–Q3 2.43–3.38) %wt. DGLA was inversely related to LA and LA:DGLA ratio. There were 208 incident cases of MACE and 55 deaths. In the multivariable analysis, the hazard ratio (HR) for the total death in the three higher quartiles (Q2–4) of DGLA as compared to Q1 was 0.54 (0.31–0.95), with p = 0.03 (Model-1), 0.50 (0.28–0.91), with p = 0.02 (Model-2), and 0.47 (0.26–0.84), with p = 0.012 (Model-3), and non-significant for MACE. Risk of MACE (Model 3) approached borderline significance for LA:DGLA in Q2–4 vs. Q1 [HR 1.42 (1.00–2.04), p = 0.052]. Conclusions: Low levels of DGLA were related to a high LA:DGLA ratio and risk of total death in elderly patients with recent MI.

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MicroRNA-146a Serves as a Biomarker for Adverse Prognosis of ST-Segment Elevation Myocardial Infarction

Cardiovascular Therapeutics ◽

10.1155/2021/2923441 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Shengjue Xiao ◽

Tongneng Xue ◽

Qinyuan Pan ◽

Yue Hu ◽

Qi Wu ◽

...

Keyword(s):

Myocardial Infarction ◽

Cox Regression ◽

Control Groups ◽

Hub Genes ◽

Cox Regression Analysis ◽

St Segment Elevation ◽

Segment Elevation Myocardial Infarction ◽

St Segment ◽

Low Levels ◽

And Control

Objective. This study is aimed at exploring the underlying molecular mechanisms of ST-segment elevation myocardial infarction (STEMI) and provides potential clinical prognostic biomarkers for STEMI. Methods. The GSE60993 dataset was downloaded from the GEO database, and the differentially expressed genes (DEGs) between STEMI and control groups were screened. Enrichment analysis of the DEGs was subsequently performed using the DAVID database. A protein–protein interaction network was constructed, and hub genes were identified. The hub genes in patients were then validated by quantitative reverse transcription-PCR. Furthermore, hub gene-miRNA interactions were evaluated using the miRTarBase database. Finally, patient data on classical cardiovascular risk factors were collected, and plasma microRNA-146a (miR-146a) levels were detected. An individualized nomogram was constructed based on multivariate Cox regression analysis. Results. A total of 239 DEGs were identified between the STEMI and control groups. Expression of S100A12 and miR-146a was significantly upregulated in STEMI samples compared with controls. STEMI patients with high levels of miR-146a had a higher risk of major adverse cardiovascular events (MACEs) than those with low levels of miR-146a (log-rank P = 0.034 ). Multivariate Cox regression analysis identified five statistically significant variables, including age, hypertension, diabetes mellitus, white blood cells, and miR-146a. A nomogram was constructed to estimate the likelihood of a MACE at one, two, and three years after STEMI. Conclusion. The incidence of MACEs in STEMI patients expressing high levels of miR-146a was significantly greater than in those expressing low levels. MicroRNA-146a can serve as a biomarker for adverse prognosis of STEMI and might function in its pathogenesis by targeting S100A12, which may exert its role via an inflammatory response. In addition, our study presents a valid and practical model to assess the probability of MACEs within three years of STEMI.

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Predicting long-term cardiovascular outcomes of patients with acute myocardial infarction using soluble ST2

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2019-0062 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Mustafa Umut Somuncu ◽

Belma Kalayci ◽

Ahmet Avci ◽

Tunahan Akgun ◽

Huseyin Karakurt ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Cox Regression ◽

High Serum ◽

Major Adverse Cardiovascular Events ◽

Lower Systolic Blood Pressure ◽

Cox Regression Analysis ◽

Killip Class ◽

Target Vessel Revascularization

AbstractBackgroundThe increase in soluble suppression of tumorigenicity 2 (sST2) both in the diagnosis and prognosis of heart failure is well established; however, existing data regarding sST2 values as the prognostic marker after myocardial infarction (MI) are limited and have been conflicting. This study aimed to assess the clinical significance of sST2 in predicting 1-year adverse cardiovascular (CV) events in MI patients.Materials and methodsIn this prospective study, 380 MI patients were included. Participants were grouped into low sST2 (n = 264, mean age: 60.0 ± 12.1 years) and high sST2 groups (n = 116, mean age: 60.5 ± 11.6 years), and all study populations were followed up for major adverse cardiovascular events (MACE) which are composed of CV mortality, target vessel revascularization (TVR), non-fatal reinfarction, stroke and heart failure.ResultsDuring a 12-month follow-up, 68 (17.8%) patients had MACE. CV mortality and heart failure were significantly higher in the high sST2 group compared to the low sST2 group (15.5% vs. 4.9%, p = 0.001 and 8.6% vs. 3.4% p = 0.032, respectively). Multivariate Cox regression analysis concluded that high serum sST2 independently predicted 1-year CV mortality [hazard ratio (HR) 2.263, 95% confidence interval (CI) 1.124–4.557, p = 0.022)]. Besides, older age, Killip class >1, left anterior descending (LAD) as the culprit artery and lower systolic blood pressure were the other independent risk factors for 1-year CV mortality.ConclusionsHigh sST2 levels are an important predictor of MACE, including CV mortality and heart failure in a 1-year follow-up period in MI patients.

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Long-Term Clinical Outcome in Elderly Patients Undergoing Mitral Valve Repair

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0040-1716324 ◽

2020 ◽

Author(s):

Julia Götte ◽

Armin Zittermann ◽

Kavous Hakim-Meibodi ◽

Masatoshi Hata ◽

Rene Schramm ◽

...

Keyword(s):

Mitral Valve ◽

General Population ◽

Elderly Patients ◽

Cox Regression ◽

Functional Class ◽

Tricuspid Valve Repair ◽

Valve Repair ◽

Cox Regression Analysis

Abstract Background Long-term data on patients over 75 years undergoing mitral valve (MV) repair are scarce. At our high-volume institution, we, therefore, aimed to evaluate mortality, stroke risk, and reoperation rates in these patients. Methods We investigated clinical outcomes in 372 patients undergoing MV repair with (n = 115) or without (n = 257) tricuspid valve repair. The primary endpoint was the probability of survival up to a maximum follow-up of 9 years. Secondary clinical endpoints were stroke and reoperation of the MV during follow-up. Univariate and multivariable Cox regression analysis was performed to assess independent predictors of mortality. Mortality was also compared with the age- and sex-adjusted general population. Results During a median follow-up period of 37 months (range: 0.1–108 months), 90 patients died. The following parameters were independently associated with mortality: double valve repair (hazard ratio, confidence interval [HR, 95% CI]: 2.15, 1.37–3.36), advanced age (HR: 1.07, CI: 1.01–1.14 per year), diabetes (HR: 1.97, CI: 1.13–3.43), preoperative New York Heart Association (NYHA) functional class (HR: 1.41, CI: 1.01–1.97 per class), and operative creatininemax levels (HR: 1.32, CI: 1.13–1.55 per mg/dL). The risk of stroke in the isolated MV and double valve repair groups at postoperative year 5 was 5.0 and 4.1%, respectively (p = 0.65). The corresponding values for the risk of reoperation were 4.0 and 7.0%, respectively (p = 0.36). Nine-year survival was comparable with the general population (53.2 vs. 53.1%). Conclusion Various independent risk factors for mortality in elderly MV repair patients could be identified, but overall survival rates were similar to those of the general population. Consequently, our data indicates that repairing the MV in elderly patients represents a suitable and safe surgical approach.

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Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

Biological Chemistry ◽

10.1515/hsz-2016-0177 ◽

2016 ◽

Vol 397 (12) ◽

pp. 1265-1276 ◽

Cited By ~ 14

Author(s):

Nancy Ahmed ◽

Julia Dorn ◽

Rudolf Napieralski ◽

Enken Drecoll ◽

Matthias Kotzsch ◽

...

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Cox Regression ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Predictive Marker ◽

Residual Tumor ◽

Mrna Levels ◽

Serous Ovarian Cancer ◽

Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

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Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

Blood ◽

10.1182/blood-2011-07-367961 ◽

2012 ◽

Vol 119 (24) ◽

pp. 5824-5831 ◽

Cited By ~ 165

Author(s):

Ana Flávia Tibúrcio Ribeiro ◽

Marta Pratcorona ◽

Claudia Erpelinck-Verschueren ◽

Veronika Rockova ◽

Mathijs Sanders ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Cox Regression ◽

Multivariable Analysis ◽

Gene Expression Signature ◽

Mutation Status ◽

Cox Regression Analysis ◽

Prognostic Effect ◽

Or Gene ◽

Acute Myeloid

Abstract The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3Amutant AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3Awild-type AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3Amutant AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3Awild-type AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.

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RISK FACTORS ASSOCIATED WITH THE OCCURRENCE OF EARLY COMPLICATIONS OF ACUTE MYOCARDIAL INFARCTION AFTER CARDIO-INTERVENTION TREATMENT

Wiadomości Lekarskie ◽

10.36740/wlek202006132 ◽

2020 ◽

Vol 73 (6) ◽

pp. 1245-1251

Author(s):

Iryna A. Holovanova ◽

Grygori A. Oksak ◽

Iryna M. Tkachenko ◽

Maxim V. Khorosh ◽

Mariia M. Tovstiak ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cox Regression ◽

Risk Indicators ◽

Interventional Treatment ◽

Early Complications ◽

Cox Regression Analysis ◽

Intervention Treatment

The aim of our study was to identify the main risk factors for the occurrence of early complications of acute myocardial infarction after cardio-interventional treatment and to evaluate prognostic risk indicators. Materials and methods: Risk factors of myocardial infarction were determined by copying the case history data and calculating on their basis of the odds ratio and ±95% confidence interval. After it, we made a prediction of the risk of early complications of AMI with cardiovascular intervention by using a Cox regression that took into account the patient’s transportation time by ambulance. Results: Thus, the factors that increase the chances of their occurrence were: summer time of year; recurrent myocardial infarction of another specified localization (I122.8); the relevance of the established STEMI diagnosis; diabetes mellitus; renal pathology; smoking; high rate of BMI. Factors that reduce the chances of their occurrence: men gender – in 35%; the age over of 70 – by 50%; the timely arrival of an emergency medical team – by 55%. The factors that increase the chances of their occurrence were: age over 70 years; subsequent myocardial infarction of unspecified site; diabetes mellitus. Using of a Cox regression analysis, it was proved that the cumulative risk of early complications of AMI with cardio-intervention treatment increased from the 10th minute of ambulance arrival at place, when ECG diagnosis (STEMI), presence of diabetes mellitus, smoking and high BMI. Conclusions: As a result of the conducted research, the risk factors for early complications of AIM with cardio-interventional treatment were identified.

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Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer

Biological Chemistry ◽

10.1515/hsz-2016-0282 ◽

2017 ◽

Vol 398 (7) ◽

pp. 765-773 ◽

Cited By ~ 6

Author(s):

Shuo Zhao ◽

Julia Dorn ◽

Rudolf Napieralski ◽

Axel Walch ◽

Sandra Diersch ◽

...

Keyword(s):

Ovarian Cancer ◽

Cox Regression ◽

Multivariable Analysis ◽

Positive Staining ◽

Mrna Levels ◽

High Grade ◽

Serous Ovarian Cancer ◽

Data Set ◽

Cox Regression Analysis ◽

Kaplan Meier

Abstract In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.

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Abstract TMP83: Long-term Risk of Venous Thromboembolism After Stroke

Stroke ◽

10.1161/str.48.suppl_1.tmp83 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Santosh B Murthy ◽

Alexander E Merkler ◽

Gino Gialdini ◽

Abhinaba Chatterjee ◽

Costantino Iadecola ◽

...

Keyword(s):

Ischemic Stroke ◽

Venous Thromboembolism ◽

Proportional Hazards ◽

Cox Regression ◽

Multivariable Analysis ◽

First Year ◽

Cumulative Rate ◽

Incident Cases

Background: There are few data on the long-term risk of venous thromboembolism (VTE) among stroke survivors. We aimed to compare the incidence of VTE amongst patients with ischemic stroke versus those with intracerebral hemorrhage (ICH). Methods: We identified all adults discharged from nonfederal acute care hospitals in CA, NY, and FL between 2005 and 2012 with previously validated ICD-9-CM codes for ischemic stroke and ICH. Our primary outcome of VTE was defined as pulmonary embolism or deep vein thrombosis. To capture incident cases of VTE, we excluded patients with a VTE prior to or during the index stroke. Kaplan-Meier survival statistics were used to calculate the cumulative rate of incident VTE. Cox regression was used to compare the risk of VTE after stroke while adjusting for demographics, vascular risk factors, and Elixhauser comorbidity index. As there was a violation of the proportional-hazards assumption, we calculated separate hazard ratios (HR) for each year of follow-up. Results: We identified 834,660 patients with stroke, of whom 712,440 (85.3%) had ischemic stroke and 112,220 (14.7%) had ICH. Over a mean follow-up of 2.8 (+/-2.4) years, 19,937 (2.4%) developed VTE. After 7 years, the cumulative rate of VTE was 4.7% (95% confidence interval [CI], 4.5-4.9%) in patients with ICH and 4.4% (95% CI, 4.3-4.5%) in patients with ischemic stroke. In multivariable analysis, VTE risk was higher in the first year after ICH compared to ischemic stroke (HR 1.51; 95% CI, 1.43-1.58). However, following the first year, the hazard of VTE was higher among patients with ischemic stroke versus those with ICH (Figure). Conclusions: The risk of VTE after stroke varies by stroke type and time. Patients with ICH have a higher risk of VTE in the first year after stroke as compared to those with ischemic stroke while patients with ischemic stroke have a higher risk beyond 1 year.

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Abstract 2284: Non-invasively Determined Ventricular Elastance as a predictor of cardiovascular mortality in Patients With acute myocardial infarction and Preserved ejection fraction: Data from Infarction Prognosis Study (IPS) registry

Circulation ◽

10.1161/circ.116.suppl_16.ii_498-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Sung Ai Kim ◽

Jong-Won Ha ◽

Hyeon Chang Kim ◽

Sungha Park ◽

Eui-Young Choi ◽

...

Keyword(s):

Myocardial Infarction ◽

Ejection Fraction ◽

Cardiovascular Mortality ◽

Cox Regression ◽

Left Ventricular ◽

Volume Index ◽

Rank Test ◽

Preserved Ejection Fraction ◽

Cox Regression Analysis ◽

Acute Mi

Background : Previous studies of the prognosis of myocardial infarction (MI) have focused primarily on patients with left ventricular (LV) systolic dysfunction. Little is known about the prognosis of patients with MI and preserved ejection fraction (EF), which is increasing. Since the ratio of mitral inflow (E) and annular velocity (E′) to stroke volume (E/E′/SV) has been reported as an index of diastolic elastance (Ed), we hypothesized that Ed has prognostic implication in patients with acute MI and preserved EF. Method : Between May 2005 and January 2007, a total of 421 patients with acute MI were prospectively enrolled in Infarction Prognosis Study (IPS) registry. Among 358 patients who had comprehensive echocardiographic study, 42 patients with significant valvular heart disease or coexisted cardiomyopathy and 50 patients with decreased EF (<40%) were excluded. This left a total of 266 patients, who constituted the study population. The primary end-point was cardiovascular mortality. Results : Median follow-up duration was 12 months. Of 266 patients, cardiovascular death occurred in 11 (4.1%) patients. Age (p< 0.001), LA volume index (p=0.001), the severity of diastolic dysfunction (grade ≥ 2, p=0.04), Ed (p=0.003) were univariate predictors of cardiovascular mortality. However, in multivariate Cox regression analysis, age (p=0.008, HR; 1.14, 95% CI; 1.03–1.25) and Ed (p=0.009, HR; 1.72, 95% CI; 1.14 –2.58) were found to be independent predictors for cardiovascular mortality in patients with acute MI and preserved EF. Cut-off value of Ed for cardiovascular mortality determined by Kaplan-Meier method (p<0.001 by log-rank test) and ROC curve (AUC 0.87, sensitivity 90%, specificity 74%) was 0.25. Conclusion : Non-invasively determined ventricular diastolic elastance is a novel and powerful independent predictor of cardiovascular mortality in patients with acute MI and preserved EF.

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A stand-alone structured educational programme after myocardial infarction: a randomised study

Heart ◽

10.1136/heartjnl-2020-318414 ◽

2021 ◽

pp. heartjnl-2020-318414

Author(s):

Georgios Giannopoulos ◽

Sofia Karageorgiou ◽

Dimitrios Vrachatis ◽

Ioannis Anagnostopoulos ◽

Maria S Kousta ◽

...

Keyword(s):

Myocardial Infarction ◽

Primary Endpoint ◽

Cardiovascular Events ◽

Cox Regression ◽

Intervention Group ◽

Educational Programme ◽

Lifestyle Changes ◽

Cerebrovascular Event ◽

Primary Analysis ◽

Cox Regression Analysis

BackgroundAcute myocardial infarction (MI) is a major clinical manifestation of coronary artery disease. Post-MI morbidity and mortality can be reduced by lifestyle changes and aggressive risk factor modification. These changes can be applied more effectively if the patient is actively involved in the process. The hypothesis of this study was that an educational programme in post-MI patients could lead to reduced incidence of cardiovascular events.MethodsPost-MI patients were prospectively randomised into two groups. Patients in the intervention arm were scheduled to attend an 8-week-long educational programme on top of usual treatment, while controls received optimal treatment. The primary endpoint was the composite of all-cause death, MI, cerebrovascular event and unscheduled hospitalisation for cardiovascular causes. Endpoint adjudication was blinded.Results329 patients (238 men) were included, with a mean follow-up time of 17±4 months. In the primary analysis, mean primary end point-free survival time was 597 days (95% CI 571 to 624) in controls, compared with 663 days (95% CI 638 to 687) in the intervention group (p<0.001). The HR in the univariate Cox regression analysis was 0.48 (95% CI 0.32 to 0.73; p=0.001). The raw rates of the primary endpoint were 20.8% (6 deaths, 13 MIs, 2 strokes and 14 hospitalisations) vs 36.6% (8 deaths, 22 MIs, 7 strokes and 22 hospitalisations), respectively (OR 0.46, 95% CI 0.28 to 0.74; p=0.002).ConclusionThese results suggest that a relatively short adult education programme offered to post-MI patients has beneficial effects, resulting in reduced risk of cardiovascular events.Trial registration numberNCT04007887.

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