Aspirin for primary prevention of ST segment elevation myocardial infarction in persons with diabetes and multiple risk factors

Controversy exists as to whether low-dose aspirin use may give benefit in primary prevention of cardiovascular (CV) events. We hypothesized that the benefits of aspirin are underevaluated. We investigated 12,123 Caucasian patients presenting to hospital with acute coronary syndromes as first manifestation of CV disease from 2010 to 2019 in the ISACS-TC multicenter registry (ClinicalTrials.gov, NCT01218776). Individual risk of ST segment elevation myocardial infarction (STEMI) and its association with 30-day mortality was quantified using inverse probability of treatment weighting models matching for concomitant medications. Estimates were compared by test of interaction on the log scale. The risk of STEMI was lower in the aspirin users (absolute reduction: 6·8%; OR: 0·73; 95%CI: 0·65-0·82) regardless of sex (p for interaction=0·1962) or age (p for interaction=0·1209). Benefits of aspirin were seen in patients with hypertension, hypercholesterolemia, and in smokers. In contrast, aspirin failed to demonstrate a significant risk reduction in STEMI among diabetic patients (OR:1·10;95%CI:0·89-1·35) with a significant interaction (p: <0·0001) when compared with controls (OR:0·64,95%CI:0·56-0·73). Stratification of diabetes in risk categories revealed benefits (p interaction=0·0864) only in patients with concomitant hypertension and hypercholesterolemia (OR:0·87, 95% CI:0·65-1·15), but not in smokers. STEMI was strongly related to 30-day mortality (OR:1·93; 95%CI:1·59-2·35) Low-dose aspirin reduces the risk of STEMI as initial manifestation of CV disease with potential benefit in mortality. Patients with diabetes derive substantial benefit from aspirin only in the presence of multiple risk factors. In the era of precision medicine, a more tailored strategy is required

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Sex Differences in Acute Heart Failure and Cardiovascular Outcomes After Myocardial Infarction

Introduction: ST-Segment Elevation Myocardial Infarction (STEMI) complicated by symptoms of acute \u201cde novo\u201d heart failure is associated with excess mortality. Yet whether development of heart failure and its outcomes differ by sex is unknown Hypothesis: We postulated that men and women have distinct cardiovascular responses to acute myocardial ischemia and hypothesized that women are at higher risk to develop acute heart failure and carry a concomitant worse survival compared with their male counterparts Methods: We examined the relationship among sex, acute heart failure and related outcomes after STEMI in patients with no prior history of heart failure recorded at baseline. Patients were recruited from a network of hospitals in the ISACS-TC registry (NCT01218776). Main outcome measures were incidence of Killip class 2 or higher at hospital presentation and risk-adjusted 30-day mortality rates estimated using inverse probability of weighting (IPW) and logistic regression models. Results: The study population consisted of 10,443 patients (3,112 women). After covariate adjustment and matching for age, cardiovascular risk factors, comorbidities, disease severity and delay to hospital presentation, the incidence of \u201cde novo\u201d heart failure at hospital presentation was significantly higher for women than for men (25.1% vs 20.0%, OR, 1.34; 95%CI: 1.21- 1.48). Women with \u201cde novo\u201d heart failure had higher 30-day mortality compared with their male counterparts (25.1% vs. 20.6%: OR, 1.29; 95%CI, 1.05 - 1.58). The sex-related difference in mortality rates were still apparent in patients with \u201cde novo\u201d heart failure undergoing reperfusion therapy after hospital presentation (21.3% vs.15.7%; OR, 1.45; 95% CI, 1.07 - 1.96). Conclusions: Women are at higher risk to develop \u201cde novo\u201d heart failure after STEMI and women with \u201cde novo\u201d heart failure have worse survival compared with their male counterparts. As so, \u201cde novo\u201d heart failure is a key feature to explain mortality gap after STEMI among women and me

Risk factors, revascularization therapies and cardiovascular mortality in countries with middle and low public health expenditure

Background: Studies from countries with high public health expenditure (PHE) have reported a decline of the rates of mortality from cardiovascular disease (CVD).Given that most mortality from CVD occurs in countries with low and middle PHE, there is a need for broader information on the relationship between variability in disease burden and outcomes in such countries. Purpose: The aim of this study was to evaluate the relation among risk factors, revascularization therapies and short-term mortality from acute coronary syndromes (ACS) in patient admitted to hospitals in middle versus low PHE countries. Methods: Data were derived from 18,704 patients admitted to 41 hospitals referring data to the ISACS-TC registry (NCT0128776). Patients were divided in two groups:low and middle PHE. Bosnia and Herzegovina,Croatia,Hungary,Italy,and Serbia have high PHE values, whereas Macedonia, Romania, Lithuania, Russian Federation, Kosovo,Moldova, and Montenegro, have low values. Main outcome measure was 30-day mortality. We used logistic-regression models to assess the effect of variables on the associations of interest. Results: There were 18,704 patients admitted to hospital for an ACS. Of these patients, 45% were in the low PHE group and 55% in the middle PHE group. Patients in middle PHE group were older (64% vs 61%), had higher prevalence of traditional risk factors, namely hypertension (75% vs 66%), hypercholesterolemia (55% vs 31%), diabetes (28.58% vs 23.10%), and positive family history of coronary artery disease (45.66% vs 17.56) as compared with patients in the low PHE group.Furthermore, patients in the middle PHE group had more frequently history of prior ischemic heart disease and higher rate of ST segment elevation myocardial infarction (STEMI) as clinical presentation (63.91 vs 61.98). The crude 30-day mortality rate was 6.97% in the middle PHE and 5,82% in the low PHE group. After multivariable adjustment for comorbidities and treatment covariates, patients in the middle PHE group had a better outcome compared with those in the low PHE group (OR 0.64; 95% CI 0.45\u20130.93).As most patients presented to hospital with STEMI we performed separate analyses for such patients and stratified outcomes in function of time to hospital presentation from initial symptom onset. The odds of mortality were still lower in patients in the middle PHE group (OR 0.41; 95% CI 0.22\u20130.76) if they presented within 6 hours from symptom onset.In contrast there were no difference in outcomes between middle and low PHE groups (OR 0.69; 95% CI 0.34\u20131.44) in patients with delayed presentation.This held true even in patients undergoing primary percutaneous intervention (OR 1.02; 95% CI 0.43\u20132.39). Conclusions: There are significant costs and infrastructure limitations that prohibit most countries with low PHE from having timely admission to hospital of patients with suspected ACS. Currently, many of the Eastern European countries are facing an enormous burden of mortality from CVD

Sex-Related Differences in Heart Failure After ST-Segment Elevation Myocardial Infarction

Background: ST-segment elevation myocardial infarction (STEMI) complicated by symptoms of acute de novo heart failure is associated with excess mortality. Whether development of heart failure and its outcomes differ by sex is unknown. Objectives: This study sought to examine the relationships among sex, acute heart failure, and related outcomes after STEMI in patients with no prior history of heart failure recorded at baseline. Methods: Patients were recruited from a network of hospitals in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776). Main outcome measures were incidence of Killip class 65II at hospital presentation and risk-adjusted 30-day mortality rates were estimated using inverse probability of weighting and logistic regression models. Results: This study included 10,443 patients (3,112 women). After covariate adjustment and matching for age, cardiovascular risk factors, comorbidities, disease severity, and delay to hospital presentation, the incidence of de novo heart failure at hospital presentation was significantly higher for women than for men (25.1% vs. 20.0%, odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.21 to 1.48). Women with de novo heart failure had higher 30-day mortality than did their male counterparts (25.1% vs. 20.6%; OR: 1.29; 95% CI: 1.05 to 1.58). The sex-related difference in mortality rates was still apparent in patients with de novo heart failure undergoing reperfusion therapy after hospital presentation (21.3% vs. 15.7%; OR: 1.45; 95% CI: 1.07 to 1.96). Conclusions: Women are at higher risk to develop de novo heart failure after STEMI and women with de novo heart failure have worse survival than do their male counterparts. Therefore, de novo heart failure is a key feature to explain mortality gap after STEMI among women and men

Machine learning in critical care: the role of diabetes and age in acute coronary syndromes

Background Patients with diabetes and non-ST elevation acute coronary syndrome (NSTE-ACS) have an increased risk of mortality and adverse outcomes following percutaneous coronary intervention (PCI). Purpose We aimed to investigate the impact of early, within 24 hours PCI compared with only routine medical treatment on clinical outcomes in a large international cohort of patients with NSTE-ACS and diabetes. Methods We identified 1,250 patients with diabetes and NSTE-ACS from a registry-based population between October 2010 and April 2016. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite outcome of 30-day all-cause mortality and left ventricular dysfunction (ejection fraction &lt;40%). We undertook analyses to explore the heterogeneity of treatment effects using meta-classification (MC) algorithms followed by propensity score matching and inverse-probability-of-treatment weighting (IPTW) from a landmark of 24 hours from hospitalization. Results Of 1,250 NSTE-ACS first-day survivors with diabetes (median age 67 years; 59%, men), 470 (37.6%) received early PCI and 780 routine medical treatment. The overall 30-day all-cause mortality rates were higher in the routine medical treatment than the early PCI group (6.3% vs. 2.5%). The prediction results of the MC algorithms accounted for only one interaction term that was statistically significant: age 6565 years. After propensity-matched analysis as well as IPTW, early PCI was associated with reduced 30-day all-cause mortality in the older age (OR: 0.35; 95% CI: 0.14 to 0.92 and 0.43; 95% CI: 0.21 to 0.86, respectively), whereas younger age had no association with the primary endpoint. Similar results were also obtained for the secondary endpoint. Conclusions Among patients with diabetes hospitalized for NSTE-ACS, an early, within 24 hours, PCI strategy is associated with reduced odds of 30-day mortality only for patients aged 65 years or over. MC algorithms provide accurate identification of treatment effect modifiers

Pharmacokinetic profile of atorvastatin in relation to SLCO1B1 C.521T>C and C.388A> variants in healthy volunteers

OATP1B1 is an influx transporter known to be implicated as important determinant of the intestinal absorption and hepatobiliary clearance of hydrophilic statins, such as atorvastatin. Several sequence variations have been discovered in the SLCO1B1 gene encoding OATP1B1, with some of them, such as c.388A>G (p.Asn130Asp) and c.521T>C (Val174Ala) associated with increased and reduced OATP1B1 activity, respectively. The aim of the study was to investigate the effects of these two SLCO1B1 SNPs on the pharmacokinetics of atorvastatin. Twenty three healthy Macedonian volunteers were genotyped for these two SNPs using TaqMan allelic discrimination assay. After ingestion of a single dose of 80 mg, the plasma concentrations of atorvastatin were measured for 48 h using LC-MS-MS and the Cmax, Tmax, t1/2, kel, MRT, Vd, CL, AUC0-48h and AUC0-~ were determined. Allele frequencies of the variants were in Hardy-Weinberg Equilibrium, with 39 and 15% for c.388A>G and c.521T>C, respectively. Low correlation between this SNP pair (R2=0.137; D’=0.700) was observed. No significant differences in the kel, t1/2, Cmax, Tmax, AUC0-48h, AUC0-~, MRT, Vd and CL between the carriers of different c.388A>G genotypes were observed. Subject with a c.521CC genotype had markedly higher values for Cmax and AUC0-48h, 140 and 67% respectively, in comparison with the carriers of the c.521TT genotype. These differences lacked statistical significance due to the size of the sample. In addition, the effects of SLCO1B1 diplotypes on pharmacokinetic parameters were investigated comparing the effects of *15 non-carriers (n=17) and *15 heterozygotes (n=6), as *15 homozygotes were not identified in the study. The dominant effect of the c.521T>C SNP was confirmed. Marginal statistical differences were observed in Cmax, AUC0-48h, AUC0-~ and CL, with Cmax and AUC0-~ 45% (p=0.062) and 38% (n=0.09) higher, and CL 30% (p=0.07) lower in *15 heterozygotes/carriers of c.521C allele. Additional studies, with a large sample size are needed to confirm this finding

Sex difference in the impact of delay to reperfusion on coronary blood flow and outcomes in ST-segment elevation myocardial infarction

Background: Delay from symptom onset to reperfusion by primary percutaneous coronary intervention (PCI) is longer in women and has been linked to increased mortality and worse clinical outcome. The mechanism underlying this association is still unclear. Purpose: We sought to investigate the impact of delay from symptom onset to hospital presentation on sex difference in TIMI flow grades and 30-day mortality after primary PCI for STEMI. Methods: The current study evaluated 2596 patients with STEMI who underwent primary PCI within 12 hours from symptom onset and had a stent implantation between 2010 and 2016 in the ISACS-TC registry (ClinicalTrials.gov, NCT01218776). Main outcomes measures were adjusted 30-day mortality rates and suboptimal post-PCI TIMI (Thrombolysis In Myocardial Infarction) flow (grades 642) estimated using inverse probability of treatment weighted (IPTW) models. Time from symptom onset to hospital presentation was classified as <2 hours, <6 hours, and <12 hours Results: Early reperfusion (<2 hours) was not associated with significant sex differences in the rates of mortality and final flow post-PCI TIMI flow (grades 642). Sex differences in outcomes differed if analyzing patients with 652-hour delay. Mortality rates were 4.0% for women versus 2.1% for men with an OR of 1.94 (95% CI: 1.09 to 3.47) in patients with <6 hours delay, and 4.6% for women versus 2.3% for men with an OR of 2.02 (95% CI: 1.24 to 3.27) in patients with <12 hours delay. The odds of TIMI 642 in women versus men were 1.40 (95% CI: 0.85 to 2.31) in patients with <6 hours delay, and 1.49 (95% CI: 0.99 to 2.24) in patients with <12 hours delay. Conclusions: Longer delays to reperfusion are associated with sex differences in the rates of 30-day mortality and worse outcome in women. Women are more vulnerable to prolonged untreated ischemia. This effect appears not to be mediated by less successful reperfusion

STATINS AND SEVERITY OF CLINICAL MANIFESTATIONS AMONG WOMEN AND MEN WITH INCIDENT CORONARY HEART DISEASE

Background: Controversies persist about the role of statins in primary prevention of atherosclerotic cardiovascular disease (ASCVD). We sought to determine whether initiation of statin therapy for primary prevention of cardiovascular disease may lead to a reduction in cardiovascular outcomes across age, sex, and risk factors. Methods: We investigated 14,542 patients aged 6540 years presenting to hospitals with ACS as first manifestation of cardiovascular disease from 2010 to 2019 in the ISACS Archives network of registries (NCT04008173). Individual risk of STEMI, acute heart failure (HF) on hospital admission and all-cause 30-day mortality were assessed using inverse probability of treatment weighting models matching for concomitant medications. Acute HF was defined as Killip class 65 2. Estimates were compared by test of interaction on the log scale. Results: Among the study population 12.5% of patients were on statin therapy. Mean (SD) estimated 10-year risk for ASCVD was 25.8 (17.9) in statin users vs 22.5 (17.1) in non-users. The risk of STEMI was much lower in the statin-users than in the non-users (relative risk [RR] ratio 0.64; 95%CI 0.58-0.71). This effect persisted in both sexes, but was substantially stronger in men (absolute reduction: 11.5%; RR ratio: 0.61, 95%CI: 0.54-0.69) than in women (absolute reduction: 6.3%; RR ratio: 0.76, 95% CI: 0.64-0.90, p interaction=0.02). These benefits translated into reductions in acute HF on hospital admission with statin therapy for both women (RR ratio 0.66, 95%CI: 0.53-0.83) and men (RR ratio 0.74, 95%CI 0.62-0.89; p interaction=0.22). No effect on the rates of STEMI or acute HF was noted in patients with 10-year ASCVD risk lower than 10% for either sex. Acute HF was predictive of mortality at 30 days both in women and in men. Conclusion: Preventive statin therapy reduces the risk of STEMI as initial manifestation of cardiovascular disease and acute HF with potential benefits in mortality. The most gain is attained in male subjects with 10-year CV risk equal or more than 10%