Risk Of MI Research Articles

PP.35.04

Objective: A relationship between blood pressure reduction and the prevention of MI has been established by previous studies. However, large differences of benefit have been reported in randomized clinical trials with RAAS blockers and we decided to explore if there was a different impact of lowering BP with ACE inhibitors and ARBs regarding the rate of MI. Design and method: This analysis included 22 major randomized clinical trials that enrolled 216 715 patients with hypertension and/or high cardiovascular risk, receiving a RAAS blocker in the active treatment (losartan, candesartan, valsartan, telmisartan, olmesartan, irbesartan, enalapril, ramipril, trandolapril, quinapril or perindopril) and reporting the rate of MI. Relative risk reduction was plotted against differences in SBP between active treatment and control for each trial and the relation between BP reduction and MI was evaluated for ACE inhibitors and ARBs with a linear regression. Results: When evaluated according to the slope of linear regressions, the correlation between the risk of MI and blood pressure reduction was similar between ARBs and ACE inhibitors. Consistently with previous studies, for every 10 mm Hg reduction of SBP, a 15% relative risk reduction for MI was observed. However, the intrinsic cardioprotective effects appeared to be different among classes. Below a minimal SBP difference of 10 mm Hg, the risk of MI was actually elevated in the ARB group with a 13% increase of MI vs comparator for a similar BP effect. Inversely, a beyond BP effect was confirmed for ACE inhibitors with a -9% reduction of MI (-13% for perindopril) vs comparator for a similar BP decrease.Conclusions: Our study confirmed a relationship of the rate of MI to the extent of SBP reduction. However, there is an apparent excess of MI below a BP difference of 10 mm Hg with ARBs while ACE inhibitors have a beyond BP benefit.

Abstract 110: Cumulative Negative Life Events and Risk of Myocardial Infarction: The Women’s Health Study

Background: Although psychosocial stressors such as negative life events predict adverse physical and mental health outcomes, significant gaps remain in the literature regarding whether such associations appear with cardiovascular disease (CVD) in middle-aged and older women, a demographic at higher risk for CVD than younger women. Hence, we investigated the relationship of cumulative negative life events and risk of myocardial infarction in the Women’s Health Study (WHS). Methods and Results: We performed a prospective, nested case-control study of apparently healthy post-menopausal women participating in the ongoing follow-up cohort of the Women’s Health Study; 26,763 women were followed for an average of 9 years to ascertain MI risk. Participants answered 12 standardized questions about negative life events within 5 years of survey completion (e.g. death/illness/accidental injury of someone close, fired from job, legal trouble, unemployment, marital infidelity, serious financial problems), and 3 questions about lifetime traumatic events (life-threatening illness, accident involving child or spouse, or victim of serious assault). Our cumulative life events score (CLES) was the count of items endorsed on all 15 questions, whereas our traumatic life events score counted positive responses to the 3 traumatic event questions. Women with a CLES score of zero were compared to women with scores >0 who were divided into tertiles; thus defining 4 categories. Among 267 women with a history of MI and 281 age and smoking matched controls, the median age of participants was 56.0 years old (Interquartile range: 51.3 - 60.6). Logistic regression analyses revealed that while increasing CLES was associated with increasing MI risk [Odds Ratio: OR unadjusted model: 1.00, 1.21, 1.52, 1.87; p-trend 0.16], the trend did not reach statistical significance. In models adjusted for CVD risk factors, there was a significant interaction with household income: CLES was associated with MI only in women with household income < $50,000 yearly (OR = 1.24, 95% CI: 1.05-1.49. The odds of MI was significantly higher in women who reported traumatic life events compared to women who did not (ORtraumatic life event score =1.65: 95% CI: 1.02, 2.68); women with traumatic life event(s) had a 65% increase in odds of MI when compared to women without, after adjusting for CVD risk factors and socio-economic status. In question specific analyses, women reporting serious financial problems as a life event had significantly higher odds of MI than women who did not (OR=2.60, 95% CI: 1.20 - 5.64). Conclusion: In this analysis among middle aged and older women, we found supportive evidence that negative cumulative life events were associated with MI risk, especially in low-income women and those suffering major traumatic life events. Further research is warranted particularly in women who also have limited socioeconomic resources.

Psoriasis and Cardiometabolic Traits: Modest Association but Distinct Genetic Architectures

Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4.185) and a prospective cohort of German Health Insurance beneficiaries (n=1.811.098). A potential genetic overlap was explored using genome-wide data from >22.000 coronary artery disease (CAD) and >4.000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3.717 controls. Controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odd’s ratio OR=2.36; 95% confidence interval CI=1.26–4.41) and myocardial infarction (MI, OR=2.26, 95% CI=1.03–4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk RR=1.11; 95%CI=1.08–1.14) and MI (RR=1.14; 95%CI=1.06–1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the MHC, there was no evidence for genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.

New oral anticoagulants versus vitamin K antagonists for treatment of acute venous thromboembolism: do they really increase the incidence of myocardial infarction?

Venous thromboembolism (VTE) is the third commonest cause of cardiovascular disease in the Western countries after coronary artery disease and stroke with 28 days mortality rate of 11 % for all VTE, and 25 % for cancerassociated VTE [1]. It is estimated that up to one-fifth of patients may have a fatal pulmonary embolism before diagnosis, or on the first day after diagnosis [2, 3]. The novel oral anticoagulants (NOACs), which include the direct thrombin inhibitor (DTI) dabigatran and the factor Xa inhibitors (FXaI) rivaroxaban, apixaban and edoxaban, are at least as effective as warfarin for the treatment of acute VTE [4–10]. Loffredo et al. in this issue, have confirmed these findings in their recent meta-analysis of these RCTs, and showed similar rates of recurrent VTE and all-cause mortality, but significantly lower rates of major bleeding with NOACs as compared with warfarin [11]. Their findings are in keeping with other meta-analyses that have examined the efficacy and safety of NOACs for the treatment of acute VTE [12–17]. The authors also found that NOACs increased the risk of MI in this cohort. However, the estimates were not significant when analyzed separately according to the drug class: DTI [risk ratio (RR) 2.49; 95 % CI 0.82–7.55] and FXaI (RR 2.62; 95 % CI 0.82–8.39). Furthermore, these trials were not designed to compare the rates of MI in the NOACs and warfarin treatment arms, and MI was a secondary safety outcome. The majority of the included trials did not describe the baseline cardiovascular disease status and concomitant use of antiplatelet drugs [4–9]. Finally, the event rates for MI were relatively small in these trials. We agree with the authors that their finding of a ‘MI signal’ among NOAC-treated patients with VTE is hypothesisgenerating, but the overall question of an association between NOACs, in particular dabigatran, and MI is debatable. Our objective is to chart the course of this controversy, to summarize past and emerging data, and to discuss planned studies that, taken together, should inform readers about this issue. A possible association between NOACs and MI was first raised in the RE-LY trial, which showed that dabigatran 150 mg b.i.d. was associated with a higher risk for MI in patients with atrial fibrillation (AF) than warfarin [hazard ratio (HR) 1.38; 95 % CI 1.00–1.91). However, a re-analysis of the RE-LY trial that was supplemented by additional data, showed no significant increase in MI risk with dabigatran (RR 1.27; 95 % CI 0.94–1.71) [18], and no significant effect on fatal MI (HR 0.76; 95 % CI 0.31–1.89) [19]. More recently, several meta-analyses have assessed an association between DTIs and MI and, overall, provide conflicting results. Atang et al. in a meta-analysis of 11 trials, showed that DTIs (dabigatran, ximelagatran, and AZD0837) significantly increase MI risk [odds ratio (OR) 1.35; 95 % Cl 1.10–1.66] [20]. Mak showed a significant increase composite risk of unstable angina, MI or cardiac death with dabigatran as compared with either placebo, enoxaparin or warfarin (OR 1.30; 95 % CI 1.04–1.63) [21]. Loffredo et al. in a separate meta-analysis, found that, compared with warfarin, the MI rate was significantly & James Douketis jdouket@mcmaster.ca

Testosterone products: increased risk of stroke and MI?

Testosterone products: increased risk of stroke and MI?

Association of Matrix Metalloproteinase 9 C-1562T Polymorphism with Genetic Susceptibility to Myocardial Infarction: A Meta-Analysis

BackgroundMyocardial infarction (MI) is the major cause of death by disease in the world. Many studies have identified the associations between matrix metalloproteinase 9 (MMP9) C-1562T polymorphisms and MI. However, the results remain inconclusive. To clarify the role of MMP9 C-1562T polymorphism in MI risk, we conducted a systematic review and large-scale meta-analysis. MethodsStudies published between January 2005 and March 2014 were obtained from the electronic databases PubMed, Medline, and Embase. The odds ratios (ORs) with 95% CIs were calculated for comparisons of the alleles and genotypes in the overall population and in ethnicity subgroups to measure the strength of genetic associations. ResultsA total of 7 related studies, including 3952 MI cases and 4977 healthy control subjects were included in our meta-analysis. Our results show a statistically significant association between T allele and MI in the overall population (OR = 1.23; 95% CI, 1.02–1.48; P = 0.03). The risk of MI was also significantly higher in patients carrying the T allele (TC + TT genotypes) than in those with the CC genotype (P < 0.05). In stratified analysis by ethnicity, we found the T allele was strongly associated with MI in white populations, whereas in Asian populations there appeared no significant association. ConclusionsOur data show that the MMP9 C-1562T polymorphism is a risk factor associated with increased MI susceptibility in the total population and white populations, although no significant association was observed in Asians populations. Further studies with larger sample sizes and assessing gene–gene and gene–environment interactions are required.

Comparison among drug-eluting balloon, drug-eluting stent, and plain balloon angioplasty for the treatment of in-stent restenosis: a network meta-analysis of 11 randomized, controlled trials.

A Bayesian network meta-analysis was performed comparing the efficacy and safety of drug-eluting balloons (DEB), drug-eluting stents (DES), or plain old balloon angioplasty (POBA) for treatment of in-stent restenosis (ISR). Optimal treatment options for ISR have not been well established. Randomized, controlled trials comparing DEB, DES, and POBA for the treatment of ISR after percutaneous coronary intervention with bare metal stent or DES were included. The primary outcome was target lesion revascularization (TLR). The pairwise posterior median odds ratio (OR) with 95% credible interval (CrI) was the effect measure. This analysis included 2,059 patients from 11 RCTs. The risk of TLR was markedly lower in patients treated with DEB (OR: 0.22, 95% CrI: 0.10 to 0.42) or DES (OR: 0.24, 95% CrI: 0.11 to 0.47) than in those treated with POBA in a random-effects model. In a comparison of DEB and DES, the risk of TLR (OR: 0.92, 95% CrI: 0.43 to 1.90) was similar. The risk of MI or all-cause mortality was lowest in the DEB group compared with the DES and POBA groups, which did not meet statistical significance. The risk of major adverse cardiac events, which was mainly driven by TLR, was also significantly lower in the DEB or and DES group (OR: 0.28, 95% CrI: 0.14 to 0.53) than in the POBA group, but it was similar between the DEB and DES groups (OR: 0.84, 95% CrI: 0.45 to 1.50). The probability of being ranked as the best treatment was 59.9% (DEB), 40.1% (DES), and 0.1% (POBA) in terms of TLR, whereas it was 63.0% (DEB), 35.3% (POBA), and 1.7% (DES) in terms of MI. Local drug delivery by DEB or DES for ISR lesions was markedly better than POBA in preventing TLR, but not for MI or mortality. Among the 2 different strategies of drug delivery for ISR lesions, treatment with DEB showed a trend of less development of MI than did treatment with DES.

Genetic variants in the DNA repair gene NEIL3 and the risk of myocardial infarction in a nested case–control study. The HUNT Study

Enhanced generation of reactive oxygen species and increased oxidative-induced DNA damage have been identified as possible contributors to atherosclerosis. The base excision repair (BER) pathway is the principal mechanism by which mammalian cells repair oxidative DNA damage. BER deficiency can potentially accelerate atherogenesis. We evaluated the association of Single Nucleotide Polymorphisms (SNPs) in genes encoding four different BER proteins (NEIL3, OGG1, APEX1 and XRCC1) with the incidence of myocardial infarction in a nested case-control study among participants of the second survey of the HUNT Study. The study population included 1624 cases and 4087 age- and sex-matched controls. For the NEIL3 SNP rs12645561, the TT genotype was associated with increased risk of MI (OR 1.47, 95% CI 1.02-2.12, p uncorrected for multiple comparisons = 0.04) both in the genotypic test (compared to the CC genotype) and in the recessive genetic model (compared to the CC and CT genotypes combined). For the other two NEIL3 SNPs (rs10013040 and rs1395479) and for the SNPs of OGG1 (rs1052133), APEX1 (rs1878703) and XRCC1 (rs25489) we observed no association with risk of myocardial infarction. We found that the NEIL3 rs12645561 SNP TT genotype was associated with increased risk of myocardial infarction. If confirmed in other studies, this association may suggest a possible role of attenuated DNA repair, and NEIL3 in particular, in atherogenesis.

Homocysteine and risk of periprocedural myocardial infarction in patients undergoing coronary stenting

Despite improvements in pharmacological and mechanical devices, the risk of periprocedural myocardial infarction (PMI) is still high, particularly in prothrombotic conditions. Hyperhomocysteinemia has been associated with enhanced platelet function, impaired endothelial function and prothrombotic status, thus increasing the risk of cardiovascular events. No study has, so far, investigated the relationship between homocysteine levels and the risk of periprocedural MI in patients undergoing percutaneous coronary intervention (PCI), and this is therefore the aim of the current study. In 1150 patients undergoing PCI, homocysteinemia was assessed at admission. Cardiac biomarkers were measured at intervals from 8 to 48 h after PCI. Periprocedural myonecrosis was defined by a troponin I increase to three times the upper limit of normal (ULN) or by 50% if elevated at the time of the procedure. PMI was defined as a CK-MB increase to three times the ULN or of 50% if elevated at the time of the procedure. We grouped patients according to tertile values of homocysteine. Higher homocysteine levels were associated with older age (P < 0.001), male sex (P = 0.02), arterial hypertension (P = 0.007), diabetes (P = 0.04), renal failure (P < 0.001), higher creatinine levels (P = 0.01), previous MI (P = 0.02), previous PCI (P = 0.04) and previous cerebrovascular accidents (P = 0.01). Homocysteine was associated with lower ejection fraction (P < 0.001), treatment with angiotensin-receptor blockers (P < 0.001), nitrates (P = 0.008) and diuretics (P < 0.001) and acetylsalicylic acid (P = 0.01). Homocysteine levels were directly related with the extent of coronary disease (P = 0.04) and coronary calcifications (P < 0.001) but inversely with type C lesions (P = 0.001), TIMI 3 flow pre-PCI (P = 0.02), stenosis severity (P = 0.01) and thrombus (P = 0.004). In addition, they are associated with higher rates of balloon predilatation (P = 0.02), lower use of thrombectomy (P = 0.01) and periprocedural administration of GPIIbIIIa inhibitors (P = 0.02). Ageing, male sex, diabetes, renal failure, creatinine levels, diuretics use, coronary calcifications and type C lesions were independently related to homocysteine. Homocysteine did not affect the risk of PMI [adjusted odds ratio (OR) 1.14 (0.91-1.42), P = 0.26], or periprocedural myonecrosis [adjusted OR 1.17 (0.98-1.39), P = 0.08]. Similar results were found after propensity score adjustment [adjusted OR 1.19 (0.95-1.48), P = 0.14 for PMI and adjusted OR 1.18 (0.99-1.4), P = 0.07 for myonecrosis] and at subgroup analysis in higher risk subsets of patients. In patients undergoing PCI, the risk of PMI is not influenced by hyperhomocysteinemia.

A second look with prone SPECT myocardial perfusion imaging reduces the need for angiography in patients at low risk for cardiac death or MI

BackgroundCorrection for soft tissue signal attenuation can improve the diagnostic accuracy of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). The aim of this study was to correlate SPECT-MPI findings with clinical outcomes in patients who underwent stress imaging in the supine position, who also underwent “second look” stress imaging in the prone position. MethodsPatients without perfusion abnormalities were considered Normal (N = 270). Those with apparent supine stress perfusion abnormalities which all resolved during prone imaging formed the Normal-Prone group (N = 309). Patients with matched perfusion abnormalities during both supine and prone stress imaging were considered Abnormal (N = 169). ResultsDuring follow-up (187 ± 96 days), utilization rates for invasive coronary angiography were similar for Normal vs Normal-Prone patients (3.5% vs 3.8%; P = NS), but were significantly higher in Abnormal patients (42.4%, P < .0001). Coronary revascularization occurred in 0.78%, 0.64%, and 17.7% of Normal, Normal-Prone, and Abnormal patients, respectively (P < .001). Cardiac death or myocardial infarction occurred in 2.2%, 2.3%, and 6.3% of Normal, Normal-Prone, and Abnormal patients, respectively (P = .02). ConclusionsSecond look SPECT-MPI identifies patients at low risk for death or myocardial infarction, who infrequently require invasive coronary angiography.

Fatty acids linked to cardiovascular mortality are associated with risk factors

BackgroundAlthough saturated fatty acids (FAs) have been linked to cardiovascular mortality, it is not clear whether this outcome is attributable solely to their effects on low-density lipoprotein cholesterol (LDL-C) or whether other risk factors are also associated with FAs. The Western Alaskan Native population, with its rapidly changing lifestyles, shift in diet from unsaturated to saturated fatty acids and dramatic increase in cardiovascular disease (CVD), presents an opportunity to elucidate any associations between specific FAs and known CVD risk factors.ObjectiveWe tested the hypothesis that the specific FAs previously identified as related to CVD mortality are also associated with individual CVD risk factors.MethodsIn this community-based, cross-sectional study, relative proportions of FAs in plasma and red blood cell membranes were compared with CVD risk factors in a sample of 758 men and women aged ≥35 years. Linear regression analyses were used to analyze relations between specific FAs and CVD risk factors (LDL-C, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, systolic blood pressure, diastolic blood pressure, heart rate, body mass index, fasting glucose and fasting insulin, 2-hour glucose and 2-hour insulin).ResultsThe specific saturated FAs previously identified as related to CVD mortality, the palmitic and myristic acids, were adversely associated with most CVD risk factors, whereas unsaturated linoleic acid (18:2n-6) and the marine n-3 FAs were not associated or were beneficially associated with CVD risk factors.ConclusionsThe results suggest that CVD risk factors are more extensively affected by individual FAs than hitherto recognized, and that risk for CVD, MI and stroke can be reduced by reducing the intake of palmitate, myristic acid and simple carbohydrates and improved by greater intake of linoleic acid and marine n-3 FAs.

Comparison of long-term safety and efficacy outcomes after drug-eluting and bare-metal stent use across racial groups: Insights from NHLBI Dynamic Registry

BackgroundLong-term data on outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and bare-metal stent (BMS) across racial groups are limited, and minorities are under-represented in existing clinical trials. Whether DES has better long-term clinical outcomes compared to BMS across racial groups remains to be established. Accordingly, we assessed whether longer-term clinical outcomes are better with DES compared to BMS across racial groups. MethodsUsing the multicenter National Heart, Lung, and Blood Institute (NHLBI)-sponsored Dynamic Registry, 2-year safety (death, MI) and efficacy (repeat revascularization) outcomes of 3326 patients who underwent PCI with DES versus BMS were evaluated. ResultsWith propensity-score adjusted analysis, the use of DES, compared to BMS, was associated with a lower risk for death or MI at 2years for both blacks (adjusted Hazard Ratio (aHR)=0.41, 95% CI 0.25–0.69, p<0.001) and whites (aHR=0.67, 95% CI 0.51–0.90, p=0.007). DES use was associated with a significant 24% lower risk of repeat revascularization in whites (aHR=0.76, 95% CI 0.60–0.97, p=0.03) and with nominal 34% lower risk in blacks (aHR=0.66, 95% CI 0.39–1.13, p=0.13). ConclusionThe use of DES in PCI was associated with better long-term safety outcomes across racial groups. Compared to BMS, DES was more effective in reducing repeat revascularization in whites and blacks, but this benefit was attenuated after statistical adjustment in blacks. These findings indicate that DES is superior to BMS in all patients regardless of race. Further studies are needed to determine long-term outcomes across racial groups with newer generation stents.

Towards Understanding the Clinical Signi􀏐icance of QT Peak Prolongation- A Novel Marker of Myocardial Ischemia Independently Demonstrated in Two Prospective Studies

Background: QT peak prolongation identiied patients at risk of death or non-fatal MI. We tested the hypothesis that QT peak prolongation might be associated with signiicant myocardial ischaemia in two separate cohorts to see how widely applicable the concept was. Methods and Results: In theirst study, 134 stroke survivors were prospectively recruited and had 12-lead ECGs and Nuclear myocardial perfusion scanning. QT peak was measured in lead I of a 12-lead ECG and heart rate corrected by Bazett's formula (QTpc). QTpc prolongation to 360ms or more was 92% speciic at diagnosing severe myocardial ischaemia. This hypothesis-generating study led us to perform a second prospective study in a different cohort of patients who were referred for dobutamine stress echocardiography. 13 of 102 patients had signiicant myocardial ischaemia. Signiicant myocardial ischaemia was associated with QT peak prolongation at rest (mean 354ms, 95% CI 341-367ms, compared with mean 332ms, 95% CI 327-337ms in those without signiicant ischaemia; p=0.002). QT peak prolongation to 360ms or more was 88% speciic at diagnosing signiicant myocardial ischaemia in the stress echocardiography study. QT peak prolongation to 360ms or more was associated with over 4-fold increase odds ratio of signiicant myocardial ischaemia. The Mantel- Haenszel Common Odds Ratio Estimate=4.4, 95% CI=1.2-16.0, p=0.023. Conclusion: QT peak (QTpc) prolongation to 360ms or more should make us suspect the presence of signiicant myocardial ischaemia. Such patients merit further investigations for potentially treatable ischaemic heart disease to reduce their risk of subsequent death or non-fatal MI.

Lipid and lipoprotein measurements and the risk of ischemic vascular events: Framingham Study.

To examine the relationship between plasma lipid measurements and incident ischemic vascular events (ischemic stroke [IS], and as a positive control, myocardial infarction [MI]) in a community cohort. In 6,276 stroke-free Framingham participants (aged 64 ± 10 years, 56% female), we related plasma lipid levels (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and TC/HDL-C ratio) measured at the original cohort 15th (1977-1979) and 20th examination cycles (1986-1990) and (TC, HDL-C, TC/HDL-C ratio, triglycerides [TG], and low-density lipoprotein cholesterol [LDL-C]) measured at the offspring fourth examination (1995-1998), to 10-year risk of incident IS and MI. Utilizing genome-wide genotyping in the same subjects, we used mendelian randomization methods to assess whether observed associations were incidental or causal. During a mean follow-up of 9 years, 301 participants experienced incident IS. In multivariable-adjusted analyses, HDL-C ≤40 mg/dL and TC/HDL ratio ≥5 were associated with increased risk of IS (hazard ratio [95% confidence interval]: 1.59 [1.23-2.05], p < 0.001 and 1.47 [1.15-1.87], p < 0.001), but not TC or LDL-C. In adjusted analysis, a strong association between TG and IS was diminished. In the MI-free sample (n = 5,875, aged 64 ± 10 years, 58% female; 403 MI events), all lipid markers were associated with MI risk. A genetic risk score comprising 47 known determinants of circulating HDL-C was not associated with IS. In a middle-aged to elderly community sample, we observed that low HDL-C and high TC/HDL-C ratio, but not LDL-C or TG were associated with risk of incident IS. We observed the usual associations between lipids and risk of MI. Our findings suggest an important, but less likely causal, role of HDL-C over other lipid biomarkers for optimal stroke risk stratification.

PTSD and Risk of Incident Cardiovascular Disease in Aging Veterans

To determine if late-life posttraumatic stress disorder (PTSD) is associated with cardiovascular disease in a sample of older veterans, and whether the association is independent of medical and psychiatric comorbities. Retrospective cohort study conducted using the Department of Veterans Affairs (VA) National Patient Care Database (2000-2011). VA medical centers in the United States. A total of 138,341 veterans 55 years and older without cardiovascular disease at study baseline (2000-2003). PTSD and cardiovascular disease (as defined by diagnoses of: cerebrovascular disease [CVD], congestive heart failure [CHF], myocardial infarction [MI], and peripheral vascular disease [PVD]) were identified by ICD-9 codes during study baseline (2000-2003) and follow-up (2004-2011), respectively. 3% of veterans (N= 4,041) had a baseline diagnosis of PTSD. Unadjusted increased risk of incidence of CVD was 80%, CHF was 56%, MI was 82%, and PVD was 60% in veterans with PTSD compared with those without PTSD. After adjustment for demographics, medical comorbidities, substance use, and psychiatric comorbidities, veterans with late-life PTSD were at a 45% increased risk for incident CVD, 26% increased risk for incident CHF, 49% increased risk for incident MI, and 35% increased risk for PVD compared with veterans without late-life PTSD. Findings highlight the longitudinal impact of PTSD on increasing the incidence of cardiovascular disease in older adults. This study implies the need for greater monitoring and treatment of PTSD in older persons, particularly older veterans, to assist in preventing adverse outcomes, such as cardiovascular disease, over the long term.

Sitagliptin and cardiovascular outcomes in diabetic patients with chronic kidney disease and acute myocardial infarction: A nationwide cohort study

BackgroundThe cardiovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, in type 2 diabetic patients with chronic kidney disease (CKD) after acute myocardial infarction (AMI) are unclear. MethodsWe analyzed data from the Taiwan National Health Insurance Research Database between March 1st, 2009 and December 31st, 2011. A total of 1025 AMI patients with diabetes with chronic kidney disease were selected as the study cohort. The study evaluated the cardiovascular safety and efficacy of sitagliptin by comparing 205 subjects (20%) who use sitagliptin to 820 matched subjects (80%) who do not. The primary outcomes included myocardial infarction, ischemic stroke or cardiovascular death. ResultsPrimary composite outcomes occurred in 54 patients in the sitagliptin group (26.3%) and in 164 patients in the comparison group (20.0%) (HR, 1.32; 95% CI, 0.97–1.79; P=0.079) during the mean follow-up of 1.02years (SD=0.71years). The sitagliptin group had similar risks of ischemic stroke, all-cause mortality or hospitalization for heart failure (HF) compared to the non-sitagliptin group (P=0.938, 0.523 and 0.795 respectively). However, sitagliptin use was associated with increased risks of recurrent myocardial infarction (HR, 1.73; 95% CI, 1.15–2.58; P=0.008) and percutaneous coronary revascularization (HR, 1.43; 95% CI, 1.04–1.95; P=0.026). ConclusionsAmong type 2 diabetic patients with CKD after AMI, the use of sitagliptin was not associated with an increased risk of cardiovascular death, ischemic stroke or hospitalization for HF but was associated with increased risks of recurrent MI and percutaneous coronary revascularization.

Sex-specific differences in the effects of local androgen metabolism in the heart as an indicator for the risk of myocardial infarction

Aim Testosterone influences cardiovascular risk and disease in a sex-specific manner. The more potent androgen 5α-dihydrotestosterone (DHT) can be formed through conversion of testosterone by the enzyme 5α-reductase. We hypothesized that, because of the presence of DHT in coronary and myocardial tissues, a sexually dimorphic effect can be observed if differences exist in genetics or mRNA expression in androgen-metabolizing enzymes. Materials and methods mRNA levels of steroidogenic enzymes and the androgen receptor (AR) were investigated in human myocardial tissue samples. Subsequently, all participants in the baseline cohort of the Rotterdam Study (RSI) with successful genotyping and without prevalent myocardial infarction (MI, N=5199) were recruited to study the association between single nucleotide polymorphisms (SNPs) within SRD5A1, SRD5A2, and AKR1C3 and incident MI using Cox regression models. Significant results were replicated within the Atherosclerosis Risk in Communities cohort and the second cohort of the RSII. Results The expression of SRD5A1, AKR1C3, and AR was found in all myocardial samples, whereas HSD17B3 and SRD5A2 expression levels were low and undetectable, respectively. Myocardial SRD5A1 expression was higher in women than in men. Within SRD5A1, SNP rs248805G>A was significantly associated with incident MI in western European women (hazard ratio 1.49; 95% confidence interval 1.19-1.87). This SNP is tightly linked to the HinfI polymorphism in SRD5A1 (rs248793G>C), of which the minor allele has been associated with a higher DHT/T ratio. Conclusion Genetic variation in SRD5A1 is associated with an increased risk of MI in western European women, possibly because of the sex-specific potential of local androgen conversion and effect.

Interaction of type 2 diabetes mellitus with chromosome 9p21 rs10757274 polymorphism on the risk of myocardial infarction: a case-control study in Chinese population.

BackgroundMyocardial infarction (MI) is a serious complication of Coronary Artery Disease (CAD). Previous studies have identified genetic variants on chromosome 9p21 and 6p24 that are associated with CAD, but further studies need to be conducted to investigate whether these genetic variants are associated with the pathogenesis of MI. We therefore performed this study to assess the association between the risk of MI and SNP rs10757274 on chromosome 9p21 and SNP rs6903956 on chromosome 6p24, and to explore the gene-environment interactions in a Chinese population.MethodsA hospital-based case–control study, consisting of 502 MI patients and 308 controls, was conducted in a Chinese population. Demographic, behavioral information and clinical characteristics were collected, and genotyping of the two SNPs was performed using single base primer extension genotyping technology. The unconditional logistic regression (ULR) method was adopted to assess the association of the two SNPs with MI risk. Both generalized multifactor dimensionality reduction (GMDR) and ULR methods were applied to explore the effect of gene-environment interactions on the risk of MI.ResultsAfter adjusting for covariates, it was observed that SNP rs10757274 on chromosome 9p21 was significantly associated with MI. Compared with subjects carrying the AA genotype, subjects carrying the GA or GG genotypes had a higher MI risk (ORa = 1.52, 95% CI:1.06–2.19, pa = 0.0227; ORa = 2.40, 95% CI:1.51–3.81, pa = 0.0002, respectively). Furthermore, a two-factor gene-environment interaction model of CDKN2A/B (rs10757274) and type 2 diabetes mellitus (T2DM) was identified to be the best model by GMDR (p = 0.0107), with a maximum prediction accuracy of 59.18%, and a maximum Cross-validation Consistency of 10/10. By using the ULR method, additive interaction analysis found that the combined effect resulted in T2DM-positive subjects with genotype GG/GA having an MI risk 4.38 times that of T2DM-negative subjects with genotype AA (ORadd = 4.38, 95% CI:2.56–7.47, padd < 0.0001).ConclusionsThese results show that gene polymorphism of CDKN2A/B (rs10757274) is associated with MI risk in a Chinese population. Furthermore, T2DM is likely to have an interaction with CDKN2A/B (rs10757274) that contributes to the risk of MI.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2261-14-170) contains supplementary material, which is available to authorized users.

Abstract 12693: Influence of Resting Heart Rate and Changes in Resting Heart Rate on Cardiovascular Outcomes From the Atherosclerosis Risk in Communities Study

Background: Resting heart rate (HR) and change in resting heart rate (ΔHR) over time are associated with increased risk of adverse outcome in patients with established heart failure (HF). We assessed whether the most recent HR and ΔHR are associated with cardiovascular (CV) outcomes in participants enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Methods: We studied 15,680 participants with HR recorded at baseline (age 54±6 years, women 55%, African American 27%) and over 3 follow-up visits with a median time interval between visits of 3.0 (IQR 2.9-4.0) years. ΔHR from the preceding visit was calculated. Participants were followed up for a median of 22.7 (19.8-23.7) years. We related baseline and most recent resting HR and ΔHR to all cause mortality and CV outcomes adjusting for established baseline and time-updated risk factors and medications. Results: Baseline and most recent HR and ΔHR were associated with all-cause mortality and CV outcomes (table), however most recent HR and ΔHR were more strongly associated with outcomes compared to baseline HR. Every 10bpm increase in HR from the preceding visit was associated with a 29%, 30% 22% and 15% increase risk of all-cause mortality, incident HF, incident MI and stroke respectively. Every 10 bpm higher most recent HR was associated with a 34%, 41% 23% and 14% increase risk of all-cause mortality, incident HF, incident MI and stroke respectively. Conclusion: In a community-based cohort, the most recent resting HR and ΔHR are strongly associated with outcomes; higher resting HR and increases in HR over time are associated with the greatest magnitude of risk.

Is there any difference between the early age myocardial infarction and late age myocardial infarction in terms of psychiatric morbidity in patients who have survived acute myocardial infarction?

ObjectiveWe aimed to compare the rates of psychiatric morbidity in patients who had early age and late age MI in patients who have survived acute myocardial infarction? MethodsOne hundred sixteen patients who were hospitalized in the coronary care unit were included in the study. Psychiatric assessment of the patients was carried out within 1–6months post-MI. Psychiatric interviews were conducted with the Structured Clinical Interview for DSM-IV (SCID-I). Also used were the Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Inventory (STAI), and Health Anxiety Inventory (HAI). ResultsA total of 116 patients were divided into two groups according to age as an early age myocardial infarction group (EA-MI) and a late age myocardial infarction group (LA-MI). The EA-MI group included 24 patients 45years of age and under. The LA-MI group included 92 patients over 45years of age. Current psychiatric disorders, lifetime psychiatric disorders and lifetime depressive disorders were significantly more frequent in the EA-MI group than in the LA-MI group. ConclusionEA-MI patients have experienced a depressive episode prior to the onset of the MI, whereas in the LA-MI group, the patients typically experienced depressive episodes after MI. Our findings suggest that depression may increase the risk of MI at an early age.