Nonfatal Myocardial Infarction Events Research Articles

Association Between Long-Term Visit-to-Visit Hemoglobin A1c and Cardiovascular Risk in Type 2 Diabetes: The ACCORD Trial.

Background: To explore the association between visit-to-visit variability of glycated hemoglobin (HbA1c) and cardiovascular outcomes in the patients with type 2 diabetes mellitus (T2DM) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.Methods: We conducted a post-hoc analysis on the ACCORD population including 9,544 participants with T2DM. Visit-to-visit variability of HbA1c was defined as the individual SD, coefficient of variation (CV), and variability independent of the mean (VIM) across HbA1c measurements. The clinical measurements included primary outcome [the first occurrence of non-fatal myocardial infarction (MI), non-fatal stroke or cardiovascular death], total mortality, cardiovascular death, non-fatal MI event, non-fatal stroke, total stroke, heart failure, macrovascular events, and major coronary events (CHD).Results: Over a median follow-up of 4.85 years, 594 and 268 participants experienced all-cause mortality and cardiovascular mortality, respectively. After adjusting for baseline HbA1c levels and confounding factors, the adjusted hazard ratio (HR) comparing patients in the highest vs. the lowest quartile CV of HbA1c variability was 1.61 (95% CI 1.29–2.00) for the primary outcome. Similar trends for secondary outcome were also observed. There was no association between HbA1c fluctuation and non-fatal stroke. Noticeably, there was 66% greater risk for the all-cause mortality among patients in the highest vs. the lowest quartile (HR 1.66, 95% CI 1.27–2.17).Conclusions: Greater variability of HbA1c is associated with higher risk for cardiovascular complications and all-cause death in T2DM. Our study stresses the significance of well-controlled glycemic levels for improving cardiovascular outcomes. Further randomized clinical trials are required to confirm these findings.

High-dose versus low-dose iron sucrose in individuals undergoing maintenance haemodialysis: a retrospective study

BackgroundIntravenous iron sucrose is becoming a prevailing treatment for individuals undergoing maintenance haemodialysis, but comparisons of dosing regimens are lacking. The aim of this retrospective review was to evaluate the safety and efficacy of proactively administered high-dose iron sucrose versus reactively administered low-dose iron sucrose in patients undergoing maintenance haemodialysis.MethodsWe analysed the data of 1500 individuals with maintenance haemodialysis who were treated with either high-dose iron sucrose that was proactively administered (Group HD) or low-dose iron sucrose that was reactively administered (Group LD) at the First Affiliated Hospital of Chongqing Medical University from Jan 1, 2008, to Dec 31, 2020. The primary endpoints were the cumulative doses of iron and erythropoiesis-stimulating agent; the secondary endpoints were the events of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, infection rate, and death from any cause.ResultsOf the 2124 individuals, 624 individuals were excluded because they met one or more of the exclusion criteria, thus resulting in 1500 individuals who were eligible for inclusion in the study (Group HD, n = 760 and Group LD, n = 740). The median follow-up for the two cohorts was 32 months (range: 25–36). A significant median difference was detected in the monthly iron dose between the groups (1121 mg [range: 800–1274] in the HD group vs. 366 mg [range: 310–690] in the LD group; p < 0.05). The median dose of an erythropoiesis-stimulating agent was 26,323 IU/month (range: 17,596-44,712) in the HD group and 37,934 IU/month (range: 22,402-59,380) in the LD group (median difference: − 7901 IU/month; 95% CI: − 9632--5013; p = 0.000). A significant difference was detected in the secondary endpoints (266 events in 320 cases in the HD group vs. 344 events in 385 cases in the LD group) (HR: 0.62; 95% CI: 0.51–0.79; p < 0.001). A significant difference was not observed in death from any cause (HR: 0.57; 95% CI: 0.48–1.00; p = 0.361).ConclusionsFor individuals undergoing maintenance haemodialysis, high-dose iron sucrose that was proactively administered may be superior to low-dose iron sucrose that was reactively administered with low doses of erythropoiesis-stimulating agent.

Abstract 14959: Effect of Empagliflozin on Total Events of Myocardial Infarctions by Subtype in the EMPA-REG OUTCOME Trial

Introduction: In EMPA-REG OUTCOME®, the sodium-glucose transporter inhibitor, empagliflozin (EMPA), reduced the risk of first cardiovascular (CV) events primarily CV mortality and hospitalization for heart failure in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease. In analyses including total events, EMPA also reduced the risk of myocardial infarction (MI). Here we report the effects of EMPA on the total number of MIs by subtype. Methods: Patients were randomized to receive EMPA 10 mg, EMPA 25 mg, or placebo. We assessed the effect of pooled EMPA versus placebo on total (first plus recurrent) events of fatal and non-fatal MI using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post-hoc, we analyzed established subtypes of MI: Type 1: Typically related to plaque-rupture or thrombus; Type 2: Supply-demand; Type 3: Sudden-death related (i.e., fatal MI); Type 4: Percutaneous coronary intervention related; and Type 5: Coronary artery bypass graft related. Except type 3 MIs, MIs were non-fatal. The MIs, including subtypes, were centrally adjudicated and could be assigned to more than one subtype. Results: 7,020 patients were treated. Overall, there was 421 total events of MIs. Specifically, 299, 86, 26, 19, and 1 of the MIs were classified as type 1, 2, 3, 4, and 5 MIs, respectively (not mutually exclusive). Overall, EMPA reduced the risk of total events of MI by 21% versus placebo (rate ratio [95% CI], EMPA versus placebo: 0.79 [0.620; 0.998], p=0.0486; each MI only counted once). The overall reduction in total events of MIs by EMPA was driven by the effect on type 1 and 2 MIs, as well as type 3 MIs, with limited number of type 4 and 5 MIs (Figure). Conclusions: EMPA reduced the risk of total MI events with consistent effects across the most common etiologies, the type 1 (plaque-rupture or thrombus) and 2 (supply-demand) MIs.

Abstract 13636: Evolocumab Shows No Significant Cost-effectiveness for Myocardial Infarction in China

Introduction: The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab has been demonstrated to reduce the incidence of cardiovascular events. This study sought to evaluate the value of evolocumab in the healthcare perspective by conducting a long-term cost-effectiveness analysis in Chinese patients with myocardial infarction (MI). Hypothesis: We assessed the hypothesis that evolocumab was inefficient for the secondary prevention of MI. Methods: A Markov cohort state-transition model was developed in decision analysis software. The model subjects could have non-fatal MI and/or stroke events, as well as die from cardiovascular disease or other causes. We integrated Chinese population specific demographics and event rates with the risk reduction of evolocumab based on large trials and meta-analysis. Age-related change, event costs and utilities were included from published sources. The model had 1-year cycle and the time horizon was 25 years. The primary outcome was the incremental cost-effectiveness ratio (ICER), defined as cost per quality-adjusted life-year (QALY) saved. Results: At its current list price (33,748 CNY annually per person), the ICER was 927,713 CNY per QALY gained. In one-way deterministic sensitivity analyses, the ICER was closely associated with the utility of cardiovascular disease event free and the cost of cardiovascular death. Probabilistic sensitivity analyses demonstrated that the probability of the cost-effectiveness of evolocumab was 1.96% at the present willingness-to-pay threshold of 212,676 CNY per QALY gained. To achieve the cost-effectiveness threshold, a net value-based price of 10,255 CNY annually would be required, which is 70% lower than the present price. Alternative scenarios analyses of treatment benefit showed in MI patients with poorly controlled familial hypercholesterolemia (FH), the ICER for evolocumab was 187,736 CNY per QALY gained, which achieved the accepted cost-effectiveness threshold. Conclusions: In conclusion, the cost-effectiveness ratio of evolocumab is less favorable in MI; However, it showed good cost-effectiveness in MI patients with poorly controlled FH in China.

Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease.

This study examines the predictive value of a novel systemic immune-inflammation index (SII, platelet×neutrophil/lymphocyte ratio) in coronary artery disease (CAD) patients. A total of 5602 CAD patients who had undergone a percutaneous coronary intervention (PCI) were enrolled. They were divided into two groups by baseline SII score (high SII vs low SII) to analyse the relationship between SII groups and the long-term outcome. The primary outcomes were major cardiovascular events (MACE) which includes nonfatal myocardial infarction (MI), nonfatal stroke and cardiac death. Secondary outcomes included a composite of MACE and hospitalization for congestive heart failure. An optimal SII cut-off point of 694.3×109 was identified for MACE in the CAD training cohort (n=373) and then verified in the second larger CAD cohort (n=5602). Univariate and multivariate analyses showed that a higher SII score (≥694.3) was independently associated with increased risk of developing cardiac death (HR: 2.02; 95% CI: 1.43-2.86), nonfatal MI (HR: 1.42; 95% CI: 1.09-1.85), nonfatal stroke (HR: 1.96; 95% CI: 1.28-2.99), MACE (HR: 1.65; 95% CI: 1.36-2.01) and total major events (HR: 1.53; 95% CI: 1.32-1.77). In addition, the SII significantly improved risk stratification of MI, cardiac death, heart failure, MACE and total major events than conventional risk factors in CAD patients by the significant increase in the C-index (P<.001) and reclassification risk categories by significant NRI (P<.05) and IDI (P<.05). SII had a better prediction of major cardiovascular events than traditional risk factors in CAD patients after coronary intervention.

P5479Educational attainment is an independent predictor of adverse outcomes in patients with coronary artery disease

Abstract Background Educational attainment is an indicator of socioeconomic status and is inversely associated with cardiovascular risk factors and risk for incident coronary artery disease (CAD). Whether the level of educational attainment (EL) in patients with CAD influences outcomes remains understudied. Purpose To ascertain the relationship between EL and adverse outcomes in patients with CAD. We hypothesize that EL will be inversely associated with adverse outcomes in this high-risk patient population. Methods Subjects undergoing cardiac catheterization for known or suspected CAD were recruited in a cardiovascular biobank and had their highest level of educational attainment assessed using predefined options of elementary/middle school, high school, college, or graduate education. The primary outcome of interest was all-cause mortality and secondary outcomes included a composite of cardiovascular deaths and nonfatal myocardial infarction (MI) events, and nonfatal MI events during follow-up. Cox proportional hazards regression models were used to analyze the association between EL and adverse outcomes after adjustment for demographic characteristics, cardiovascular risk factors, cardiovascular medication use, and estimated zip code-based annual family income. Results Among the 6,318 subjects (mean age 64 years, 63% male, 23% black) enrolled, 998 (16%) had received graduate or a higher qualification, 2,689 (43%) had received a college education, 2,403 (38%) had received a high school education, and 228 (3%) had received elementary/middle school education. During a median follow-up of 3 years,there were 1,110 deaths from all causes, 851 cardiovascular deaths/nonfatal MI, and 286 nonfatal MI events. After adjusting for covariates and compared to patients with graduate education or higher, those with lower EL (elementary/middle school, high school, or college education) had a higher risk of all-cause mortality [hazard ratio 1.66, (95% CI 1.08, 2.54), 1.58 (95% CI 1.22, 2.04), and 1.45 (95% CI 1.13, 1.57), respectively]. Similar findings were observed for secondary outcomes. EL dichotomized at graduate education was associated with all-cause mortality (hazard ratio 1.48, 95% CI 1.16, 1.88), but this relationship was significantly modified by sex (p-interaction 0.023) and the association was attenuated among male patients (hazard ratio 1.23, 95% CI 0.94, 1.61) but not female patients (hazard ratio 2.70, 95% CI 1.53, 4.77). Conclusions Lower educational attainment is an independent predictor of adverse outcomes in patients with CAD. The causal link between low education level and increased CV risk needs further investigation. Acknowledgement/Funding Dr. Quyyumi is supported by NIH grants 5P01HL101398-02, 1P20HL113451-01, 1R56HL126558-01, 1RF1AG051633-01, R01 NS064162-01, R01 HL89650-01, HL095479-0

Long-term clinical outcomes in patients with untreated non-culprit intermediate coronary lesion and evaluation of predictors by using virtual histology-intravascular ultrasound; a prospective cohort study

BackgroundIt is uncertain whether the coronary lesion with intermediate stenosis is more likely to cause cardiovascular events than a normal or minimal lesion. We conducted a single-center, prospective cohort study to identify long-term clinical outcomes of patients with untreated non-culprit intermediate lesion and evaluate its predictor of cardiovascular events by using virtual histology-intravascular ultrasound (VH-IVUS).MethodsSubjects with non-culprit intermediate lesion underwent VH-IVUS were prospectively registered after percutaneous coronary intervention at the culprit lesion. Intermediate lesion was defined as 30 to 70% stenosis in coronary angiography and primary outcome was an occurrence of major adverse cardiovascular events (MACE) defined as all-cause death, intermediate lesion revascularization (InLR), minimal lesion revascularization (MnLR, unplanned revascularization elsewhere in the target vessel or in other coronary arteries which looked normal or minimal stenosis), cerebrovascular events, or non-fatal myocardial infarction (MI). The mean follow-up period was 4.2 years.ResultsTotal 25 MACE, approximately 7% incidence annually, were identified during a follow-up period in 86 patients with 89 intermediate lesions. InLR (n = 13) was a most common event followed by MnLR (n = 6), non-fatal MI (n = 4), all-cause death (n = 3), and cerebrovascular events (n = 1). Diameter stenosis (OR 1.07, 95% CI 1.01–1.12, p = 0.015), plaque burden (PB, OR 1.07, 95% CI 1.00–1.15, p = 0.040), fibrofatty area (FFA, OR 1.61, 95% CI 1.10–2.38, p = 0.016), PB ≥ 70% (OR 3.93, 95% CI 1.28–12.07, p = 0.018), and area stenosis ≥ 50% (OR 2.94, 95% CI 1.01–8.56, p = 0.042) showed significant relationships with an occurrence of MACE. In multivariable Cox-proportional hazard analysis, FFA in intermediate lesion was an only independent predictor of MACE (HR 1.36, 95% CI 1.05–1.77, p = 0.019).ConclusionsUntreated intermediate lesions had a significantly higher chance for requiring revascularization compared with a normal or minimal lesion. And also, a large FFA in intermediate lesion was a significant predictor of cardiovascular events and which finding was mainly driven by coronary-related events, in particularly intermediate lesion progression.

The Hypercholesterolemia Paradox in Percutaneous Coronary Intervention: An Analysis of a Multicenter PCI Registry.

Objective The aim of this study was to assess the relationship between hypercholesterolemia (HC) and clinical events through a percutaneous coronary intervention (PCI) registry. HC is a well-known independent risk factor for long-term cardiovascular events after PCI. However, it has been reported to be associated with a lower risk of adverse events in patients with cancer or acute coronary syndrome.Methods We analyzed the relationship between HC and adverse events in patients treated with everolimus-eluting stents (EESs) through the Tokyo-MD PCI study (an all-comer, multicenter, observational registry). The propensity score method was applied to select two groups with similar baseline characteristics.Results The unadjusted population included 1,536 HC patients and 330 non-HC patients. Propensity score matching yielded 314 matched pairs. After baseline adjustment, the outcomes of HC patients were significantly better than those of the non-HC patients with respect to the primary endpoint, which was a combination of mortality from all causes, nonfatal myocardial infarction (MI), nonfatal neurological events, and major bleeding [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.39-0.81; p=0.002], and the secondary endpoints, which included a combination of mortality from all causes, nonfatal MI, and nonfatal neurological events (HR 0.59, 95% CI 0.39-0.88; p=0.01), and major bleeding (HR 0.42, 95% CI 0.20-0.88; p=0.02). A subgroup analysis showed age as an interaction factor for the primary endpoint (interaction p=0.035).Conclusion HC was associated with better outcomes in patients who underwent EES implantation, even after baseline adjustment.

Higher event rate in patients with high-risk Duke Treadmill Score despite normal exercise-gated myocardial perfusion imaging.

This prospective study was carried out to find the negative predictive value of various Duke Treadmill Scores (DTSs) in patients with normal myocardial perfusion imaging (MPI). This study was conducted from August 2012 to July 2015, and 603 patients having normal exercise MPIs were included. Patients were followed for 2 years for fatal myocardial infarction (FMI) and nonfatal myocardial infarction (NFMI). Follow-up was not available in 23 patients, leaving a cohort of 583 participants. DTS was low risk (≥5) in 286, intermediate risk (between 4 and − 10) in 211, and high risk (≤−11) in 86 patients. Patients with high- and intermediate-risk DTS were significantly elder than low-risk DTS cohort. Patients with high-risk DTS had significantly higher body mass index with male preponderance compared to other groups. No significant difference was found among three groups regarding modifiable or nonmodifiable risk factors and left ventricular ejection fraction. On follow-up, single FMI was observed in high-risk DTS group (log-rank test value = 5.779, P = 0.056). Five NFMI events were observed in high-risk DTS (94.2% survival; log-rank test value = 19.398, P = 0.0001; significant) as compared to two events each in low- and intermediate-risk DTS (nonsignificant). We conclude that patients with normal exercise MPI and low-to-intermediate risk DTS have significantly low NFMI. High-risk DTS despite normal exercise MPI had high NFMI. Further, validation studies to find the predictive value of symptomatic and asymptomatic ST deviation resulting in high-risk DTS in patients with normal exercise MPI are warranted.

Impact of Calcified Target Lesions on the Outcome of Percutaneous Coronary Intervention for Acute Coronary Syndrome: Insights From the BASE ACS Trial.

We performed a post hoc analysis of outcome in patients with, versus those without, calcified target lesions from the BASE ACS trial. The outcome of contemporary stent implantation in patients with calcified lesions presenting with acute coronary syndrome is unknown. The BASE ACS trial randomized 827 patients (1:1) presenting with acute coronary syndrome to receive either titanium-nitride-oxide-coated stents or everolimus-eluting stents. Calcified lesions were defined as moderate or severe calcification in the vessel wall by coronary angiography. The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, non-fatal myocardial infarction or ischemia-driven target lesion revascularization. Follow-up was planned at 12 months, and yearly thereafter for up to 7 years. Of 827 patients enrolled in the trial, 352 (42.6%) had calcified target lesions. Median follow-up was 5.0 years. The incidence of MACE was higher in patients with, versus those without, calcified target lesions (19.6% vs. 12.2%, respectively, P = 0.004). This was driven by more frequent cardiac death and non-fatal myocardial infarction events (P < 0.05, both). The rates of ischemia-driven target lesion revascularization were comparable (P > 0.05). MACE and the other endpoints were comparable between the 2 propensity-score matched subgroups (P > 0.05 for all). Hypertension and smaller vessel size independently predicted MACE in patients treated for calcified lesions. Patients presenting with acute coronary syndrome who were treated for calcified lesions had worse long-term clinical outcome, compared with those treated for non-calcified lesions, mainly due to more frequent safety events. In the propensity score-matched analysis, the outcome was comparable.

Cardiorespiratory fitness and nonfatalcardiovascular events: A population-based follow-up study

To examine the prognostic value of cardiorespiratory fitness (CRF) with risk of first major nonfatal myocardial infarction (MI), stroke, and heart failure (HF) events. Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed at baseline in a prospective cohort of 2,089 men aged 42 to 61years. During a mean (SD) follow-up of 19.1(8.4) years, 522 nonfatal acute MI events, 198 acute all-cause nonfatal stroke events, and 221 nonfatal HF events were recorded. The hazard ratio per 1-metabolic-equivalent increase in CRF was 0.93 (95% CI 0.88-0.97) for nonfatal MI, 0.94 (95% CI0.87-1.01) for nonfatal stroke, and 0.84 (95% CI 0.78-0.91) for nonfatal HF events after adjustment for cardiovascular risk factors (age, systolic blood pressure, body mass index, history of cardiovascular disease, diabetes, smoking, alcohol use, serum creatinine, low-density lipoprotein levels, physical activity, and socioeconomic status). Further adjustment for left ventricular hypertrophy and resting heart rate did not attenuate these associations. Addition of CRF to conventional cardiovascular disease risk factors significantly improved both discrimination (C index) and category free net reclassification index (cf-NRI) for nonfatal MI (change in C index, 0.015 [95% CI 0.010-0.020] and change in cf-NRI 0.27, P<.01) and HF (change in C index 0.040 [95% CI 0.010-0.060] and change in cf-NRI 0.88, P<.01). In this Finnish population, there is a strong, inverse, and independent association between CRF and acute nonfatal MI and HF risk.

Usefulness of Post-coronary Dilation to Prevent Recurrent Myocardial Infarction in Patients Treated With Percutaneous Coronary Intervention for Acute Coronary Syndrome (from the BASE ACS Trial)

Stent underexpansion is associated with worse outcome after stent implantation. Whether post-dilation (PD) improves outcome in patients with acute coronary syndrome (ACS) remains unclear. We performed post hoc analysis of outcome in patients from the BASE ACS (A prospective randomized comparison of titanium-nitride-oxide-coated bioactive stents with everolimus-eluting stents in acute coronary syndrome) trial who underwent PD versus those who did not. The BASE ACS trial randomized 827 patients (1:1) with ACS to receive either titanium-nitride-oxide-coated bioactive stents or everolimus-eluting stents. The primary end point was major adverse cardiac events (MACE): a composite of cardiac death, nonfatal myocardial infarction (MI), or ischemia-driven target lesion revascularization. Follow-up was planned at 12months and yearly thereafter for up to 7years. Of 827 patients enrolled in the BASE ACS trial, 357 (43.2%) underwent PD. Median follow-up duration was 5years. Patients who underwent PD had less frequent nonfatal MI events at long-term follow-up, compared with those who did not (4.5% vs 8.5%, respectively, p= 0.02). The rates of MACE (15.7% vs 15.1%, respectively, p= 0.81), and the other endpoints, were not significantly different (p >0.5 for all). The results were consistent in propensity score-matched analysis (270 pairs). In patients treated with bioactive stents, those who underwent PD had a trend for a fewer nonfatal MI events (p= 0.076). Comparably, in patients treated with everolimus-eluting stents, MACE and all the individual end points were comparable (p >0.5 for all). In conclusion, patients treated with early percutaneous coronary intervention for ACS who underwent PD had less frequent nonfatal MI events at long-term follow-up, compared with those who did not; MACE rates were not significantly different.

Long-term clinical outcome of elderly patients with acute coronary syndrome treated with early percutaneous coronary intervention: Insights from the BASE ACS randomized controlled trial: Bioactive versus everolimus-eluting stents in elderly patients

BackgroundThe BASE ACS trial demonstrated an outcome of titanium–nitride–oxide-coated bioactive stents (BAS) that was non-inferior to everolimus-eluting stents (EES) in patients presenting with acute coronary syndrome (ACS). We performed a post hoc analysis of elderly versus non-elderly patients from the BASE ACS trial. MethodsWe randomized 827 patients (1:1) presenting with ACS to receive either BAS or EES. The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, non-fatal myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR). Follow-up was planned at 12months and yearly thereafter for up to 7years. Elderly age was defined as ≥65years. ResultsOf the 827 patients enrolled in the BASE ACS trial, 360 (43.5%) were elderly. Mean follow-up duration was 4.2±1.9years. MACE was more frequent in elderly versus younger patients (19.7% versus 12.0%, respectively, p=0.002), probably driven by more frequent cardiac death and non-fatal MI events (5.3% versus 1.5%, and 9.7% versus 4.5%, p=0.002 and p=0.003, respectively). The rates of ischemia-driven TLR were comparable (p>0.05). In propensity score-matched analysis (215 pairs), only cardiac death was more frequent in elderly patients (6% versus 1.4%, respectively, p=0.01). Diabetes independently predicted both MACE and cardiac death in elderly patients. ConclusionsElderly patients treated with stent implantation for ACS had worse long-term clinical outcome, compared with younger ones, mainly due to a higher death rate.

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. A global consortium of 19 studies identified by November 2014. Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

HbA1c below 7% as the goal of glucose control fails to maximize the cardiovascular benefits: a meta-analysis.

ObjectiveWhether lowering glycosylated haemoglobin (HbA1c) level below 7.0 % improves macro-vascular outcomes in diabetes remains unclear. Here, we aimed to assess the effect of relatively tight glucose control resulting in a follow-up HbA1c level of less or more than 7.0 % on cardiovascular outcomes in diabetic patients.Research design and methodsWe systematically searched Medline, Web of science and Cochrane Library for prospective randomized controlled trials published between Jan 1, 1996 and July 1, 2015 that recorded cardiovascular outcome trials of glucose-lowering drugs or strategies in patients with type 2 diabetes mellitus.ResultsData from 15 studies involving 88,266 diabetic patients with 4142 events of non-fatal myocardial infarction, 6997 of major cardiovascular events, 3517 of heart failure, 6849 of all-cause mortality, 2084 of non-fatal stroke, 3816 of cardiovascular death were included. A 7 % reduction of major cardiovascular events was observed only when relatively tight glucose control resulted in a follow-up HbA1c level above 7.0 % (OR 0.93, 95 % CI 0.88–0.98; I2 = 33 %), however, the patients can benefit from reduction incidence of non-fatal myocardial infarction only when the follow-up HbA1c value below 7.0 % (OR 0.85, 95 % CI 0.74–0.96). Apart from the HbA1c value above 7.0 % (OR 1.22, 95 % CI 1.06–1.40), the application of thiazolidinediones (OR 1.39, 95 % CI 1.14–1.69) also increased the risk of heart failure, while the gliptins shows neutral effects to heart failure (OR 1.14, 95 % CI 0.97–1.34).ConclusionsRelatively tight glucose control has some cardiovascular benefits. HbA1c below 7.0 % as the goal to maximize the cardiovascular benefits remains suspended.

The economic impact of implementing a multiple inflammatory biomarker-based approach to identify, treat, and reduce cardiovascular risk

Objectives:To develop an economic model to estimate the change in the number of events and costs of non-fatal myocardial infarction (MI) and non-fatal ischemic stroke (IS) as a result of implementing routine risk-stratification with a multiple inflammatory biomarker approach.Methods:Reductions in the numbers of non-fatal MI and non-fatal IS events and in related per-member-per-month (PMPM) and 5-year costs (excluding test costs) due to biomarker testing were modeled for a US health plan with one million beneficiaries. Inputs for the model included literature-based MI and IS incidence rates, healthcare costs associated with MI and IS, laboratory results of biomarker testing, MI and IS hazard ratios related to biomarker levels, patient monitoring and intervention costs and use/costs of preventative pharmacotherapy. Preventative pharmacotherapy inputs were based on an analysis of pharmacy claims data. Costs savings (2013 USD) were assessed for patients undergoing biomarker testing compared to the standard of care. Data from MDVIP and Cleveland Heart Lab supported two critical inputs: (1) treatment success rates and (2) the population distribution of biomarker testing. Incidence rates, hazard ratios, and other healthcare costs were obtained from the literature.Results:For a health plan with one million members, an estimated 21,104 MI and 22,589 IS events occurred in a 5-year period. Routine biomarker testing among a sub-group of beneficiaries ≥35 years old reduced non-fatal MI and IS events by 2039 and 1869, respectively, yielding cost savings of over $187 million over 5 years ($3.13 PMPM), excluding test costs. Results were sensitive to changes in treatment response rates. Nonetheless, cost savings were observed for all input values.Conclusions:This study suggests that health plans can realize substantial cost savings by preventing non-fatal MI and IS events after implementation of routine biomarker testing. Five-year cost savings before test costs could exceed $3.13 PMPM.

Sigmoidal Maximal Effect Modeling of Low‐Density Lipoprotein Cholesterol Concentration and Annual Incidence of Coronary Heart Disease Events in Secondary Prevention Trials

To evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) concentration and the annual incidence of combined coronary heart disease (CHD) events—death or nonfatal myocardial infarction (NFMI)—by using sigmoidal maximal effect (sEmax) modeling of published data in various populations at risk for CHD events, and to use the best performing sEmax model generated to calculate the number needed to treat (NNT) to prevent a single CHD death or NFMI event across a range of LDL-C concentrations. Literature-based modeling analysis. A total of 95,955 patients from 22 published cardiovascular secondary prevention trials. Four distinct sEmax models were created based on intervention approach and CHD event risk for each trial population. Model outputs included the following: Emax (maximum CHD death/NFMI rate), E0 (minimum CHD death/NFMI rate), and fit parameters. The best-fitting sEmax model was compared with linear, log-linear, and logit models, and it was used for calculation of annualized NNT to prevent one CHD death or NFMI event with statins. The best fitting sEmax model was constructed from nine statin intervention trials in 60,483 clinically stable patients with CHD or CHD risk equivalents (Emax = 4.84%/year [95% confidence interval (CI) 4.11–5.41%/year], E0 = 1.24%/year [95% CI 0.64–1.83%/year]) and was superior to linear, log-linear, and logit models. Reduction of CHD death/NFMI incidence diminished at an LDL-C level near 90 mg/dl and became near static at an LDL-C level of 60–70 mg/dl. Annual NNT for LDL-C reduction from a baseline of 130–100 mg/dl, 90, and 70 mg/dl was 129, 104, and 83, respectively, and from a baseline of 100–70 mg/dl was 232. An sEmax model fully characterized the relationship between LDL-C concentration and incidence of CHD death or NFMI in a high-risk population receiving statins, with diminishing event reduction at an LDL-C level less than 90 mg/dl, and limited projected event reduction beyond an LDL-C level of ~60–70 mg/dl. As baseline LDL-C level declines, the NNT sharply increases.

Systemic review/Meta-analysis Pregnancy-associated plasma protein A predicts adverse vascular events in patients with coronary heart disease: a systematic review and meta-analysis

IntroductionProspective studies about the association between elevated circulating pregnancy-associated plasma protein A (PAPP-A) and adverse vascular events in patients with coronary heart diseases (CHD) are inconsistent. We performed a meta-analysis to clarify this issue.Material and methodsWe identified prospective studies by searching MEDLINE. The vascular outcomes included all-cause mortality, combination of all-cause mortality and non-fatal myocardial infarction (MI), and combined cardiovascular events. Prospective studies providing multivariable adjusted relative risks (RRs) and their 95% confidence intervals (CIs) of pre-mentioned outcomes were included. A random-effects model was used to calculate the pooled RRs. Subgroup and sensitivity analyses were used to explore the potential sources of heterogeneity or modifiable factors.ResultsFourteen studies with a total of 12 830 participants were included. Elevated PAPP-A level was associated with all-cause mortality (pooled RR 1.74, 95% CI: 1.45 to 2.09, p < 0.001), combined all-cause mortality and non-fatal MI (RR 1.59, 95% CI: 1.37 to 1.85, p < 0.001) and combined cardiovascular events (RR 1.50, 95% CI: 1.22 to 1.85, p < 0.001). There was no significant heterogeneity. Subgroup and sensitivity analyses showed that the positive association was not affected by follow-up term, CHD type, different assay methods of PAPP-A, or studies with less than 5 adjusted variables.ConclusionsElevated serum PAPP-A level is associated with adverse vascular outcomes in patients with CHD.

Meta-Analysis of Multiple Primary Prevention Trials of Cardiovascular Events Using Aspirin

Several meta-analyses have focused on determination of the effectiveness of aspirin (acetylsalicylic acid) in primary prevention of cardiovascular (CV) events. Despite these data, the role of aspirin in primary prevention continues to be investigated. Nine randomized trials have evaluated the benefits of aspirin for the primary prevention of CV events: the British Doctors' Trial (BMD), the Physicians' Health Study (PHS), the Thrombosis Prevention Trial (TPT), the Hypertension Optimal Treatment (HOT) study, the Primary Prevention Project (PPP), the Women's Health Study (WHS), the Aspirin for Asymptomatic Atherosclerosis Trial (AAAT), the Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial, and the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial. The combined sample consists of about 90,000 subjects divided approximately evenly between those taking aspirin and subjects not taking aspirin or taking placebo. A meta-analysis of these 9 trials assessed 6 CV end points: total coronary heart disease, nonfatal myocardial infarction (MI), total CV events, stroke, CV mortality, and all-cause mortality. No covariate adjustment was performed, and appropriate tests for treatment effect, heterogeneity, and study size bias were applied. The meta-analysis suggested superiority of aspirin for total CV events and nonfatal MI, (p <0.05 for each), with nonsignificant results for decreased risk for stroke, CV mortality, and all-cause mortality. There was no evidence of a statistical bias (p >0.05). In conclusion, aspirin decreased the risk for CV events and nonfatal MI in this large sample. Thus, primary prevention with aspirin decreased the risk for total CV events and nonfatal MI, but there were no significant differences in the incidences of stroke, CV mortality, all-cause mortality and total coronary heart disease.

Adiponectin Multimeric Forms but not Total Adiponectin Levels are Associated with Myocardial Infarction in Non-Diabetic Men

Multimer complex formation of adiponectin is recognized as an important mechanism modulating the biological functions of this adipokine, but the role of adiponectin isoforms in myocardial infarction (MI) is still unclear. We quantified total adiponectin (TOTAL), high, middle, and low molecular weight adiponectin multimers (HMW, MMW, LMW) in a study of non-diabetic obese (BMI ≥ 30 kg/m(2)) and normal-weight (BMI ≤ 25 kg/m(2)) male subjects with MI and healthy controls (n=180). Subsequently, we designed a prospective nested-case-control study to investigate the association of the adiponectin multimers with fatal and non-fatal MI in n=1236 initially healthy non-diabetic men. Obesity was significantly related to lower levels of TOTAL, HMW, MMW, and LMW in subjects with and without MI (p < 0.01, each). In contrast, MI was strongly related to MMW/TOTAL (p < 0.0001), inversely to HMW/TOTAL (p < 0.0001), but not TOTAL or LMW levels. In particular, the median MMW/HMW ratios were markedly different in men with MI (1.71, interquartile range (1.08-2.40)) and without (0.72 (0.49-1.08), p < 0.0001). In the prospective study, 56 incident fatal and non-fatal MI events occured. The MMW/HMW ratio was associated with fatal and non-fatal MI up to 5 years before the event. The β-estimates for the relationship between MMW/HMW and incident MI decreased with increasing time to the event. Whereas total adiponectin and all isoforms are related to obesity, total adiponectin and LMW levels are not associated with MI in non-diabetic men. In contrast, the MMW/HMW-ratio correlated with incident MI up to 5 years before the event. These data imply that measurement of adiponectin multimers adds significant value in assessing cardiovascular risk compared to total adiponectin alone.