Greater Risk Of Myocardial Infarction Research Articles

Long-term use of proton pump inhibitors, dose-response relationship and associated risk of ischemic stroke and myocardial infarction.

Use of proton pump inhibitors (PPIs) has been associated with cardiovascular disease amongst patients not on antiplatelet therapy. The associations of PPI use, duration and dose, with risk of first-time ischemic stroke and myocardial infarction (MI) are poorly understood. All Danish individuals with no prior history of MI or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI use and its dose and used multiple cause-specific Cox regression and g-formula methods to analyze long-term use. Amongst 214998 individuals, during a median follow-up of 5.8years, there were 7916 ischemic strokes and 5608 MIs. Current PPI exposure was associated with significantly higher rates of both ischemic stroke (Hazard ratio (HR) 1.13; 95% confidence interval (CI) 1.08-1.19) and MI (HR 1.31, CI 1.23-1.39) after adjusting for age, sex, comorbidities and concomitant medication. High-dose PPI was associated with increased rates of ischemic stroke (HR 1.31, CI 1.21-1.42) and MI (HR 1.43, CI 1.30-1.57). Histamine H2 receptor antagonists (H2RAs) use was not significantly associated with ischemic stroke (HR 1.02, CI 0.84-1.24) or MI (HR 1.15, CI 0.92-1.43). Long-term users of PPIs, compared with nonusers, had a 29% (CI 5%-59%) greater absolute risk of ischemic stroke and a 36% (CI 7%-73%) greater risk of MI within a 6-month period. Use of PPIs was associated with increased risks of first-time ischemic stroke and MI, particularly amongst long-term users and at high doses.

Temporal Biomarker Profiling Reveals Longitudinal Changes in Risk of Death or Myocardial Infarction in Non-ST-Segment Elevation Acute Coronary Syndrome.

There are conflicting data on whether changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) concentrations between time points (delta NT-proBNP and hs-CRP) are associated with a change in prognosis. We measured NT-proBNP and hs-CRP at 3 time points in 1665 patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Cox proportional hazards was applied to the delta between temporal measurements to determine the continuous association with cardiovascular events. Effect estimates for delta NT-proBNP and hs-CRP are presented per 40% increase as the basic unit of temporal change. Median NT-proBNP was 370.0 (25th, 75th percentiles, 130.0, 996.0), 340.0 (135.0, 875.0), and 267.0 (111.0, 684.0) ng/L; and median hs-CRP was 4.6 (1.7, 13.1), 1.9 (0.8, 4.5), and 1.8 (0.8, 4.4) mg/L at baseline, 30 days, and 6 months, respectively. The deltas between baseline and 6 months were the most prognostically informative. Every +40% increase of delta NT-proBNP (baseline to 6 months) was associated with a 14% greater risk of cardiovascular death (adjusted hazard ratio (HR) 1.14, 95% CI, 1.03-1.27) and with a 14% greater risk of all-cause death (adjusted HR 1.14, 95% CI, 1.04-1.26), while every +40% increase of delta hs-CRP (baseline to 6 months) was associated with a 9% greater risk of the composite end point (adjusted HR 1.09, 95% CI, 1.02-1.17) and a 10% greater risk of myocardial infarction (adjusted HR 1.10, 95%, CI 1.00-1.20). Temporal changes in NT-proBNP and hs-CRP are quantitatively associated with future cardiovascular events, supporting their role in dynamic risk stratification of NSTEACS. ClinicalTrials.gov identifier NCT00699998.

Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data

Objective To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs).Design Systematic review followed by a one stage bayesian...

Diabetes as Cardiovascular Risk Factor: A Review

This study was conducted at Department of Zoology, University of Gujrat, Pakistan in 2017. The data regarding diabetes as cardiovascular risk factor was obtained and compiled through a thorough review of various published research articles of international reputed journals and relevant books. Cardiovascular disease is the leading cause of morbidity in diabetic patients. Diabetic patients have greater risk of myocardial infarction than non-diabetics. Hyperglycemia, dyslipidemia, hypertension, insulin resistance are considered as metabolic syndrome that causes coronary artery disease, cerebral vascular disease and peripheral arterial disease and ultimately leads to death. Cardiovascular diseases can be treated by changing lifestyle and by using different hypoglycemic agents and different therapies.

Soft drinks and sweetened beverages and the risk of cardiovascular disease and mortality: a systematic review and meta-analysis.

Soft drink consumption is associated with adverse health behaviours that predispose to adverse cardiovascular risk factor profiles; however, it is unclear whether their intake independently leads to an increased risk of cardiovascular events and mortality. We conducted a systematic review and meta-analysis to evaluate this. Medline and EMBASE were searched in July 2015 for studies that considered soft drink intake and risk of mortality, myocardial infarction (MI) or stroke. Pooled risk ratios (RRs) for adverse outcomes were calculated using inverse variance with a random effects model, and heterogeneity was assessed using the I2 statistic. A total of seven prospective cohort studies with 308,420 participants (age range 34-75 years) were included in the review. The pooled results suggest a greater risk of stroke (RR 1.13, 95% CI 1.02-1.24), and MI (RR 1.22, 95% CI 1.14-1.30), but not vascular events with incremental increase in sugar-sweetened beverage (SSB) consumption. With incremental increase in artificially sweetened beverage (ASB) consumption, there was a greater risk of stroke (RR 1.08, 95% CI 1.03-1.14), but not vascular events or MI. In the evaluation of high vs. low SSB, there was a greater risk of MI (RR 1.19, 95% CI 1.09-1.31) but not stroke, vascular events or mortality. For ASB, there was a significantly greater risk of stroke (RR 1.14, 95% CI 1.04-1.26) and vascular events (RR 1.44, 95% CI 1.02-2.03) but not MI or mortality. Our results suggest an association between consumption of sugar-sweetened and ASBs and cardiovascular risk, although consumption may be a surrogate for adverse health behaviours.

Circulation Research “In This Issue” Anthology

Circulation Research “In This Issue” Anthology

Role of methylenetetrahydrofolate reductase 677C→T polymorphism in the development of myocardial infarction: evidence from an original study and updated meta-analysis

The methylenetetrahydrofolate reductase (MTHFR) gene variant 677C→T is considered a risk factor for myocardial infarction (MI) in Caucasians, but it remains unclear whether this applies to Chinese or other Asian populations. A total of 551 controls and 304 age-matched Chinese MI patients were recruited. MTHFR genotypes were determined. A subsequent meta-analysis was performed to determine the association between MTHFR and MI in Asia. Conventional risk factors such as hypertension, diabetes mellitus and low-density lipoprotein exhibited no significant differences between the two groups. Genotype frequencies among cases and controls were compatible with Hardy–Weinberg equilibrium. The frequencies of CC, CT and TT genotypes were 28, 46 and 26 % for patients with MI and 31, 52 and 17 % for the matched control group (p = 0.006). T-allele frequency in MI patients was higher than in controls (49 vs. 43 %, odds ratio = 0.785, 95 % confidence interval = 0.644–0.958, p = 0.017). A total of 16 studies including ours were identified, involving 4053 patients and 6791 controls. A recessive genotype model of MTHFR 677C→T polymorphism, but not a dominant genotype model, was significantly associated with greater MI risk in Asians. MI risk increased 48, 37 and 47 % for the TT homozygote compared with the CC wild type, CT heterozygote and the combination of CT and CC. Thus, we conclude that the MTHFR gene variant 677C→T is a risk factor for MI in the Chinese population and the TT genotype is associated with a significant increase in MI risk in Asia.

Obesity or smoking: Which factor contributes more to the incidence of myocardial infarction?

ObjectiveComparing the contributions of smoking and obesity to the risk of myocardial infarction (MI) can help prioritize behavioral modifications. The objective of this study was to determine the relative risk of smoking, obesity and the joint burden on the risk of MI. MethodsThis is a retrospective cohort study of data accessed from electronic medical records of the largest health care organization in Israel. The study population included all 738,380 members of Clalit Health Services, with at least one smoking status and one BMI assessment recorded in 2009 or 2010, aged 40–74years, who were MI-free before 2009. Obesity was defined as BMI >30kg/m2. New and primary MI between January 1 and December 31, 2011 were recorded. ResultsRates of MI were: 0.18% for non-obese never smokers, 0.25% for obese never smokers, 0.40% for non-obese past smokers, 0.50% for obese past smokers, 0.53% for non-obese current smokers and 0.66% for obese current smokers. Among non-obese individuals, past smokers and current smokers had a greater risk of MI than did never smokers, after adjusting for age, gender and socioeconomic position (OR, 1.45; 95% CI, 1.23–1.70 and OR, 2.35; 95% CI, 2.10–2.63, respectively). The burden of obesity increased the risk of MI for never smokers but the burden of obesity did not elevate the risk of MI when combined with current or past smoking groups, after adjusting for comorbidities. ConclusionsPast and, more so, current smoking confers greater risk for MI than obesity.

Myocardial infarction and mortality following joint surgery in patients with rheumatoid arthritis: a retrospective cohort study.

BackgroundRheumatoid arthritis (RA) is associated with an increased risk of myocardial infarction (MI) and post-MI fatality compared with the general population. In a previous study examining post-MI treatment in RA compared with controls we noted that a higher proportion of the RA patients had experienced MI following a surgical procedure. The aim of this study was to compare the risk of MI and mortality at 6 weeks and 12 months following joint surgery in patients with RA compared with the general population.MethodsIndividuals who had undergone joint surgery in Victoria, Australia between 1 July 2000 and 30 June 2007 were identified from routinely collected hospital administrative data. Logistic regression analysis was performed to examine odds of 6 week and 12 month MI and mortality in RA versus non-RA patients with adjustment for age, sex, comorbidities, socioeconomic status, patient type and admission type. Subgroup analysis of total hip and knee arthroplasty episodes was undertaken.ResultsA total of 308,589 episodes of joint surgery occurred among 240,571 individuals, with 3654 (1.2 %) occurring among patients with RA. At 6 weeks post joint surgery the adjusted odds ratio (OR) for MI was 1.50 (95 % CI 0.96–2.33), all-cause death was 1.85 (95 % CI 1.09–3.13) and cardiovascular death was 1.90 (95 % CI 1.07–3.37). At 12 months post joint surgery the adjusted OR of MI was 1.70 (95 % CI 1.27–2.28), all-cause death was 2.18 (95 % CI 1.66–2.86) and cardiovascular death was 2.30 (95 % CI 1.65–3.22). On analysis of joint surgeries other than hip or knee arthroplasty, people with RA were at greater risk of MI within 6 weeks (adjusted OR 2.32; 95 % CI 1.24–4.34) and 12 months (adjusted OR 2.20; 95 % CI 1.47–3.30) compared to those without RA, but no difference in odds of short term mortality were found.ConclusionsFollowing an episode of joint surgery RA patients have a significantly increased risk of death at 6 weeks, and MI and death at 12 months, compared to the general population. The reasons for this remain to be elucidated but in the meantime RA patients should be considered at higher risk in the perioperative period.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0958-5) contains supplementary material, which is available to authorized users.

Reply

We reported an effect of proton pump inhibitors (PPIs) leading to vascular dysfunction (Circulation 2013;128:845–853). Based on that finding, we hypothesized that PPIs may be associated with an increased risk of myocardial infarction, and reapplied a validated data-mining method to examine for the presence of a drug safety signal in electronic medical records. With regard to the critique of our paper (PLoS One 2015;10:e0124653), the commentators have attributed many of the limitations of observational studies to our data-mining study. However, we believe that they fail to account for the unique merits of data mining methodology as a tool to identify safety signals with medications and to advance pharmacovigilance. First, let us review the difference between observational studies and data-mining studies. Data-mining studies (or algorithmic modeling as described by Breiman in Statistical Science 2001;16:199–231) treat the causal mechanism as an unknown and attempt to learn a function f(x) that operates on variables (x) to predict the responses (y). Therefore, the linking function f(x) in a data-mining study should not be interpreted as a causal regression model. The commentators have critiqued our work not appreciating the distinction between the two statistical approaches. The validation of data-mining approaches is performed by measuring predictive accuracy using a set of known true and false associations. In performing such validation of data-mining studies—using a set of known associations, rather than “adjusting” for specific hypothesized confounders on a case-by-case basis—the key idea is that if confounding is present, upon testing known negative associations, those will signal as positive (or vice versa a positive association will be missed). A poorly designed data-mining process will thus make the wrong call more often than a well-designed process. This approach, of estimating how likely are we to be wrong, thus depends on the breadth of the set of true and false associations used. In 2013, we validated our data-mining pipeline using a set of 28 true-positive and 165 negative associations (specificity of 97.5%, sensitivity of 39%, with an area under the curve of 80.4%; Clin Pharmacol Ther 2013;93:547–555), and earned an editorial describing the work as representative of the cutting edge of drug safety and pharmacovigilance science (Clin Pharmacol Ther 2013;93:474–475). As described in (Clin Pharmacol Ther 2013;93:547–555) and reproduced in Supplemental Figure 1 for the PLoS article, temporality is addressed. In fact, some of the situations speculated, such as confounding owing to PPI use as first-line stress ulcer prophylaxis are avoided by the flowchart described in Supplemental Figure 1. Finally, we also assessed the issue of outcome validity by evaluating 25 outcomes by manual review in our 2013 paper (Supplemental Figure 3; Clin Pharmacol Ther 2013;93:547–555). Second, the possible mechanism that we proposed has been experimentally tested—both in vitro and in vivo, with validation by a second investigative group using a different experimental approach to assess vascular function—and published in 2013 (Circulation 2013;128:845–853). In addition, there are several studies that raise concerns about the use of PPIs in patients with coronary artery disease, as well as in the general population (Ann Intern Med 2010;153:378–386; BMJ 2011;342:d2690; Circulation 2012;125:978–986; JAMA Intern Med 2013;173:518–523). Shih et al (Int J Cardiol 2014;177:292–297) examined this association in the general population, reporting a 1.58-fold greater risk of myocardial infarction with PPI use. Short-term use of PPIs probably has little adverse cardiovascular effect. Indeed, in a small, randomized trial in healthy volunteers, the short-term exposure to PPIs did not have a significant effect on plasma asymmetric dimethylarginine and vascular function (Vasc Med 2015;20:309–316). Overall, the cardiovascular risk from PPI use in the general population remains poorly studied. Therefore, given our findings that PPIs may adversely affect vascular function, given the association seen via data-mining in two unrelated datasets, given the association seen on reanalysis of a prospective dataset, and given a separate independent study (Int J Cardiol 2014;177:292–297), the issue of cardiovascular risk from PPI use in the general population needs further investigation. We did not conclude with a recommendation to change practice based on our findings; in fact, we explicitly say that the work presented provides provide an example of how a combination of experimental studies and data-mining approaches can prioritize drug safety signals for further investigation. Given that PPIs were approved by the US Food and Drug Administration for short-term use (weeks, rather than months or years) and the current standard of practice deviates from that, if further research confirms the risk, physicians and patients should assesses the risks and benefits of long-term PPI use. Is Proton Pump Inhibitor Use Associated With Risk of Myocardial Infarction?GastroenterologyVol. 150Issue 2PreviewShah NH, LePendu P, Bauer-Mehren A, et al. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS One 2015;10:e0124653. Full-Text PDF

Association Between Glycosylated Hemoglobin and Cardiovascular Events and Mortality in Older Adults without Diabetes Mellitus in the General Population: The Leiden 85-Plus Study.

To examine the association between glycosylated hemoglobin (HbA1c) and incident cardiovascular disease and mortality in 85-year-old individuals without diabetes mellitus from the general population. Population-based prospective follow-up study. General population. Individuals without known diabetes mellitus (N=445, n=291 female). HbA1c levels were categorized into three groups (<5.0% (31mmol/mol), 5.0-5.7% (31-39mmol/mol; reference), 5.7-6.5% (39-48mmol/mol)). At baseline, a history of myocardial infarction (MI) was more prevalent in subjects in the highest HbA1c group (18%) than in the reference group (7%) (P=.001). Prospectively, those with the highest level of HbA1c at baseline had a risk of incident MI during the 5-year follow-up that was 3.6 (95% confidence interval=1.5-8.3) times as great as that of the reference group. No association was found between HbA1c level and incident stroke, cardiovascular mortality, or all-cause mortality. In individuals aged 85 and older without diabetes mellitus, higher HbA1c is associated with greater risk of MI but not with stroke and mortality.

Disparities in cardiovascular disease risk in the United States.

This is a comprehensive narrative review of the literature on the current science and evidence of population-level differences in risk factors for heart disease among different racial and ethnic population in the United States (U.S.). It begins by discussing the importance of population-level risk assessment of heart disease in light of the growth rate of specific minority populations in the U.S. It describes the population-level dynamics for racial and ethnic minorities: a higher overall prevalence of risk factors for coronary artery disease that are unrecognized and therefore not treated, which increases their likelihood of experiencing adverse outcome and, therefore, potentially higher morbidity and mortality. It discusses the rate of Acute Coronary Syndrome (ACS) in minority communities. Minority patients with ACS are at greater risk of myocardial infarction (MI), rehospitalization, and death from ACS. They also are less likely than non-minority patients to receive potentially beneficial treatments such as angiography or percutaneous coronary intervention. This paper looks at the data surrounding the increased rate of heart disease in racial and ethnic minorities, where the risk is related to the prevalence of comorbidities with hypertension or diabetes mellitus, which, in combination with environmental factors, may largely explain CHF disparity. The conclusion is that it is essential that healthcare providers understand these various communities, including nuances in disease presentation, risk factors, and treatment among different racial and ethnic groups. Awareness of these communities’ attributes, as well as differences in incidence, risk factor burdens, prognosis and treatment are necessary to mitigate racial and ethnic disparities in heart disease.

In This Issue

HomeCirculation ResearchVol. 116, No. 5In This Issue Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published27 Feb 2015https://doi.org/10.1161/RES.0000000000000050Circulation Research. 2015;116:763Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis (p 789)Sortilin protein drives cholesterol uptake in macrophages and promotes atherosclerosis, report Patel et al.Download figureDownload PowerPointA characteristic feature of atherosclerosis is the formation of foam cells that arise from cholesterol-loaded macrophages. But exactly how macrophages take up cholesterol from transporter proteins such as low-density lipoprotein (LDL) is unclear, especially since the deletion of known macrophage lipoprotein receptors in mice does not prevent foam cell formation. Patel and colleagues thus turned their attention to a protein called sortilin. This protein mediates hepatic LDL uptake and, through genome-wide association studies, has been linked with coronary artery disease. The function of sortilin in macrophages, however, was unknown. The team found that atherosclerosis-prone mice lacking sortilin—either in all cells or just macrophages—showed a significant reduction in the number of atherolsclerotic lesions compared to mice with normal levels of the protein. They also discovered that sortilin-lacking macrophages exhibited a reduction in LDL uptake, while macrophages that over-expressed sortilin actually increased their LDL uptake. These results suggest that preventing the sortilin-driven uptake of LDL in macrophages might reduce foam cell formation and thus be a novel strategy for treating, and perhaps even preventing, atherosclerosis in the future.Transcriptional reversion of cardiomyocyte fate during mammalian cardiac regeneration (p 804)O’Meara et al describe the transcriptional signature of mammalian heart regeneration.Download figureDownload PowerPointThe adult mammalian heart has a limited capacity for regeneration. In contrast, neonatal mice, within the first week of life, can completely repair their hearts after injury. During this regeneration, neonatal heart cells lose their sarcomeric structures, adopt a less-differentiated state, and reenter the cell cycle. If this same regenerative process could be recapitulated in the adult hearts, full recovery from myocardial injury might be possible. Hence to understand the mechanism underlying the regenerative capacity of the neonatal heart, O’Meara and colleagues examined changes in the global gene expression profiles of the neonatal heart after injury and during regeneration. They also studied the expression profiles of normal neonatal and adult cardiomyocytes, mouse embryonic stem cells during differentiation into cardiomyocytes, and adult cardiomyocytes induced to de-differentiate. After cross-referencing these data, the team identified a reference panel of genes involved in the differentiation and regeneration of a normal heart. They found that injury to the neonatal heart essentially reversed the differentiation process such that seven days post-injury the genes encoding sarcomeric proteins were reduced, while the expression of cell cycle genes was elevated. The team highlighted IL-13, STAT3 and STAT6 as regulators of cell cycle re-entry, but their results provide a large number of additional candidates that could be examined in future regeneration studies.Effects of DNA damage in smooth muscle cells in atherosclerosis (p 816)DNA damage promotes atherosclerotic plaque instability report Gray et al.Download figureDownload PowerPointDNA damage occurs in the vascular smooth muscle cells (VSMCs) of atherosclerotic plaques and it becomes more pervasive with disease progression. But whether such damage is a cause or consequence of the condition is unclear. It is known that DNA damage reduces cell proliferation—because cells stop cycling to repair the DNA, and this could arguably slow down plaque growth. If, however, the damage is severe, senescence and apoptosis can occur, which induces proinflammatory cytokine production and immune cell recruitment, thus exacerbating plaque growth. To better define the relationship between plaque growth and DNA damage, Gray and colleagues studied the effects of accelerating or inhibiting DNA repair in human VSMC from normal aorta and atherosclerotic plaques. As expected, they found that VSMCs from plaques had significantly higher levels of DNA damage as well as increased activation of DNA repair pathways. By accelerating this repair in a mouse model of atherosclerosis, they found that while plaque size remained the same, there was an increase in the stability of the fibrous caps of the plaques. Inhibiting repair, on the other hand, promoted plaque instability. Because unstable plaques are associated with a greater risk of myocardial infarction and stroke, preventing DNA damage, or promoting DNA repair could be a novel therapeutic strategy for enhancing plaque stability in patients with atherosclerotic disease. Previous Back to top Next FiguresReferencesRelatedDetails February 27, 2015Vol 116, Issue 5 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000050 Originally publishedFebruary 27, 2015 PDF download Advertisement

Association of metabolic syndrome with coronary artery calcification.

Association of metabolic syndrome with coronary artery calcification.

Proton pump inhibitor use represents an independent risk factor for myocardial infarction

BackgroundThere is substantial debate regarding the development of acute coronary syndrome in patients using proton pump inhibitors (PPIs) combined with clopidogrel. However, data remain limited to address the effect of PPIs alone on the subsequent risk of myocardial infarction (MI). We aimed to explore the subsequent risk of MI in PPI users who had no previous history of MI. MethodsThe records of inpatients and outpatients with PPI prescriptions were retrieved from the Taiwan National Health Insurance Research Database between 2000 and 2009. We conducted two different study designs, the first using propensity score (PS)-matching analyses and the second using case-crossover analyses. The risk of developing MI for PPI users was analyzed in the PS-matched study. The association between risk of MI and prior PPI exposure was further validated in the case-crossover study. ResultsIn the PS-matched study, we included 126,367 PPI users and 126,367 PS-matched PPI non-users. After 120days of follow-up, PPI use was associated with a 1.58-fold greater risk of MI (adjusted hazard ratio [HR]=1.58, 95% confidence interval [CI]=1.11 to 2.25). In the case-crossover study, adjusted odds ratios of PPI for MI risk were 4.61 (95% CI=1.76 to 12.07) for the 7-day window and 3.47 (95% CI=1.76 to 6.83) for the 14-day window. ConclusionsUse of PPIs may be independently associated with an increased risk of MI. However, the benefits of PPIs may greatly outweigh the risks of adverse cardiovascular effects, with number needed to harm of 4357.

Population-based approaches to understanding disparities in cardiovascular disease risk in the United States.

This is a comprehensive narrative review of the literature on the current science and evidence of population-level differences in risk factors for heart disease among different racial and ethnic population in the US. It begins by discussing the importance of population-level risk assessment of heart disease in light of the growth rate of specific minority populations in the US. It describes the population-level dynamics for racial and ethnic minorities: a higher overall prevalence of risk factors for coronary artery disease that are unrecognized and therefore not treated, which increases their likelihood of experiencing adverse outcomes and, therefore, potentially higher morbidity and mortality. It discusses the rate of acute coronary syndrome (ACS) in minority communities. Minority patients with ACS are at greater risk of myocardial infarction, rehospitalization, and death from ACS. They also are less likely than nonminority patients to receive potentially beneficial treatments such as angiography or percutaneous coronary intervention. This paper looks at the data surrounding the increased rate of congestive heart failure in racial and ethnic minorities, where the risk is related to the prevalence of comorbidities with hypertension or diabetes mellitus, which, in combination with environmental factors, may largely explain congestive heart failure disparity. The conclusion is it is essential that health care providers understand these various communities, including nuances in disease presentation, risk factors, and treatment among different racial and ethnic groups. Awareness of these communities’ attributes as well as differences in incidence, risk factor burdens, prognosis, and treatment are necessary to mitigate racial and ethnic disparities in heart disease.

Effects of Combination Antiretroviral Therapies on the Risk of Myocardial Infarction Among HIV Patients

Cohort studies have demonstrated greater risk of myocardial infarction (MI) associated with specific antiretroviral use, while meta-analyses of randomized controlled trials (RCTs) have not. These differences may be due to inherent biases in the observational study design or to the limited duration of randomized trials. We conducted a new-user, active-comparator cohort study emulating an RCT comparing the initiation of several antiretrovirals as part of combination antiretroviral therapy (cART) and MI. We included North Carolina (NC) Medicaid beneficiaries infected with human immunodeficiency virus between 2002 and 2008 who were previously untreated with cART. We compared hazard ratios (HRs) and 95% confidence intervals (CIs) of MI between abacavir and tenofovir recipients, and lopinavir-ritonavir or atazanavir recipients and nonnucleoside reverse transcriptase inhibitor (NNRTI) recipients. We adjusted for confounding through inverse probability weighting methods. There were 3481 NC Medicaid new cART recipients who contributed 6399 person-years and experienced 38 MI events. Receiving abacavir compared with tenofovir as part of cART was associated with an increased rate of MI (unadjusted HR = 2.70 [95% CI = 1.24-5.91]; adjusted HR = 2.05 [0.72-5.86]). Point estimates also suggest a relationship between receipt of atazanavir or lopinavir-ritonavir compared with an NNRTI and MI, although estimates were imprecise. We found an increased rate of MI among patients initiating abacavir compared with tenofovir, although the association was decreased after confounding adjustment. Without a very large prospective comparative clinical trial, a much larger observational study of patients initiating cART would be needed to better define this apparent association.

Varespladib and Cardiovascular Events in Patients With an Acute Coronary Syndrome

Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes. A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. clinicaltrials.gov Identifier: NCT01130246.

Total sitting time and risk of myocardial infarction, coronary heart disease and all-cause mortality in a prospective cohort of Danish adults

BackgroundEvidence suggests that sitting time is adversely associated with health risks. However, previous epidemiological studies have mainly addressed mortality whereas little is known of the risk of coronary heart disease. This study aimed to investigate total sitting time and risk of myocardial infarction, coronary heart disease incidence and all-cause mortality.MethodsIn the Danish Health Examination Survey (DANHES) conducted in 2007-2008 we tested the hypothesis that a higher amount of daily total sitting time is associated with greater risk of myocardial infarction, coronary heart disease and all-cause mortality. The study population consisted of 71,363 men and women aged 18-99 years without coronary heart disease. Participants were followed for myocardial infarction, coronary heart disease and mortality in national registers to August 10, 2012. Cox regression analyses were performed with adjustment for potential confounders and multiple imputation for missing values.ResultsDuring a mean follow-up period of 5.4 years 358 incident cases of myocardial infarction, 1,446 of coronary heart disease, and 1,074 deaths from all causes were registered. The hazard ratios associated with 10 or more hours of daily sitting compared to less than 6 hours were 1.38 (95% CI: 1.01, 1.88) for myocardial infarction, 1.07 (95% CI: 0.91, 1.27) for coronary heart disease and 1.31 (95% CI: 1.09, 1.57). Compared to sitting less than 6 hours per day and being physically active in leisure time, the hazard ratios of sitting more than 10 hours per day and also being physically inactive in leisure time were 1.80 (95% CI: 1.15, 2.82) for myocardial infarction, 1.42 (95% CI: 1.11, 1.81) for coronary heart disease, and 2.29 (95% CI: 1.82, 2.89) for all-cause mortality.ConclusionsThe results suggest that a higher amount of daily total sitting time is associated with all-cause mortality, particularly among inactive adults. In relation to coronary heart, disease results were less clear. This paper adds new evidence to the limited data on the evidence of sitting time and cardiovascular disease and mortality.

PPAR-Gamma in Ulcerative Colitis: A Novel Target for Intervention

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor, originally described in adipose tissue, that controls the expression of a large number of regulatory genes in lipid metabolism and insulin sensitization. Well known by endocrinologists, thiazolidinediones (TZDs) are classical PPARγ synthetic agonists which were currently used as insulin-sensitizing agents in the treatment of type 2 diabetes. While the clinical benefits of TZDs in treating metabolic disorders have been clearly demonstrated, new studies performed in animal models of colitis and in patients with ulcerative colitis have also revealed the key roles of PPARγ activation in the regulation of inflammation and immune response, notably in the colon through epithelial cells. During inflammation, PPAR acts directly to negatively regulate gene expression of proinflammatory genes in a ligand-dependent manner by antagonizing the activities of other transcription factors such as members of the NF-κB and AP-1 families. A major mechanism that underlies the ability of PPARs to interfere with the activities of these transcription factors has been termed transrepression. PPARγ acts by inhibiting signaldependent transcription factors that mediate inflammatory programs of gene activation. However, due to safety issues concerning particularly the greater risk of myocardial infarction, use of TZDs has been severely limited for the treatment of type 2 diabetes and/or inflammatory diseases, justifying the development of a new family of PPARγ agonists with major transrepressive effects and without toxicity. By the demonstration that the anti-inflammatory effects of 5- aminosalicylic acid (5-ASA) in patients with ulcerative colitis were mediated by PPARγ activation, several molecules having 5-ASA similarities have been developed and screened leading to the selection of a aminophenyl-alpha-methoxypropionic acids named GED-0507-34-Levo (GED). This compound activating PPARγ has 100-to 150-fold higher anti-inflammatory activity than 5-ASA. This new PPAR modulator is giving promising results both in vitro and in vivo, without toxicity and is currently evaluated in a phase 2 clinical trial. The aim of this review is to present and discuss the evidence suggesting that PPARγ targeting is of therapeutic interest in the treatment of UC.