Health effects of e-cigarettes and their use for smoking cessation from a vascular perspective.

Tobacco consumption is one of the most important risk factors for cardiovascular disease. Despite all efforts to curb any form of smoking, the number of e-cigarette users is still rising more than tabacco smoking decreases. E-cigarettes are often advertised as less harmful than regular cigarettes and helpful for smoking cessation. But e-cigarettes are not risk-free and their use causes vascular damage. There is concern about long-term health risks of e-cigarettes or when non-smokers use them as first nicotine contact. Furthermore, their use for smoking cessation is discussed controversially. To optimize treatment and medical counselling of current smokers and e-cigarette users, we present an evidence-based overview of the most important issues of e-cigarette use from a vascular medicine point of view. The key messages are presented as a position statement of the German Society of Vascular Medicine and endorsed by the European Society of Vascular Medicine.

Tayside Screening For Cardiac Events (TASCFORCE) study: a prospective cardiovascular risk screening study.

PURPOSE: Risk factor-based models struggle to accurately predict the development of cardiovascular disease (CVD) at the level of the individual. Ways of identifying people with low predicted risk who will develop CVD would allow stratified advice and support informed treatment decisions about the initiation or adjustment of preventive medication, and this is the aim of this prospective cohort study. PARTICIPANTS: The Tayside Screening for Cardiac Events (TASCFORCE) study recruited men and women aged≥40 years, free from known CVD, with a predicted 10-year risk of coronary heart disease<20%. If B-type natriuretic peptide (BNP) was greater than their gender median, participants were offered a whole-body contrast-enhanced MRI (WBCE-MRI) scan (cardiac imaging, whole-body angiography to determine left ventricular parameters, delayed gadolinium enhancement, atheroma burden). Blood, including DNA, was stored for future biomarker assays. Participants are being followed up using electronic record-linkage cardiovascular outcomes. FINDINGS TO DATE: 4423 (1740, 39.3% men) were recruited. Mean age was 52.3 years with a median BNP of 7.50 ng/L and 15.30 ng/L for men and women, respectively. 602 had a predicted 10-year risk of 10%-19.9%, with the remainder<10%. Age, female sex, ex-smoking status, lower heart rate, higher high-density lipoprotein and lower total cholesterol were independently associated with higher log10 BNP levels. Mean left ventricular mass was 129.2 g and 87.0 g in men and women, respectively. FUTURE PLANS: The TASCFORCE study is investigating the ability of a screening programme, using BNP and WBCE-MRI, at the time of enrolment, to evaluate prediction of CVD in a population at low/intermediate risk. Blood stored for future biomarker analyses will allow testing/development of novel biomarkers. We believe this could be a new UK Framingham study allowing study for many years to come. CLINICAL TRIAL REGISTRATION: ISRCTN38976321.

Management of chronic peripheral artery disease patients with indication for endovascular revascularization.

With an increasing global burden of patients with chronic peripheral artery disease (PAD) the safe and effective provision of lower limb revascularisation is a growing medical need. Endovascular procedures for the treatment of PAD have become a crucial cornerstone of modern vascular medicine, and the first line revascularisation approach if technically feasible and taking patient choice into consideration. With the increasing age of patients with PAD and the increasing number of comorbidities open vascular surgery is also often not feasible. We outline a framework of key messages, endorsed by the board of the European Society of Vascular Medicine for pre-, peri- and post procedural management of patients requiring endovascular arterial procedures of the lower limbs. These key messages emphasize the important and increasing role of interventional vascular physicians.

Lipid-lowering and anti-thrombotic therapy in patients with peripheral arterial disease: European Atherosclerosis Society/European Society of Vascular Medicine Joint Statement.

Patients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and <1.4 mmol/L (<55 mg/dL) in PAD patients. As demonstrated by randomized controlled trials, lowering LDL-C not only reduces cardiovascular events but also major adverse limb events (MALE), including amputations, of the order of 25%. Addition of ezetimibe or a PCSK9 inhibitor further decreases the risk of cardiovascular events, and PCSK9 inhibition has also been associated with reduction in the risk of MALE by up to 40%. Furthermore, statin-based treatment improved walking performance, including maximum walking distance, and pain-free walking distance and duration. This Task Force recommends strategies for managing statin-associated muscle symptoms to ensure that PAD patients benefit from lipid-lowering therapy. Antiplatelet therapy, either daily clopidogrel 75 mg or the combination of aspirin 100 mg and rivaroxaban (2 × 2.5 mg) is also indicated to prevent cardiovascular events. Dual antiplatelet therapy (aspirin and rivaroxaban) may be considered following revascularization, taking into account bleeding risk. This Joint Task Force believes that adherence with these recommendations for lipid-lowering and antithrombotic therapy will improve the morbidity and mortality in patients with PAD.

Lipid-lowering and anti-thrombotic therapy in patients with peripheral arterial disease.

Patients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and <1.4 mmol/L (<55 mg/dL) in PAD patients. As demonstrated by randomized controlled trials, lowering LDL-C not only reduces cardiovascular events but also major adverse limb events (MALE), including amputations, of the order of 25%. Addition of ezetimibe or a PCSK9 inhibitor further decreases the risk of cardiovascular events, and PCSK9 inhibition has also been associated with reduction in the risk of MALE by up to 40%. Furthermore, statin- based treatment improved walking performance, including maximum walking distance, and pain-free walking distance and duration. This Task Force recommends strategies for managing statin-associated muscle symptoms to ensure that PAD patients benefit from lipid-lowering therapy. Antiplatelet therapy, either daily clopidogrel 75 mg or the combination of aspirin 100 mg and rivaroxaban (2×2.5 mg) is also indicated to prevent cardiovascular events. Dual pathway inhibition (aspirin and rivaroxaban) may be considered following revascularization, taking into account bleeding risk. This Joint Task Force believes that adherence with these recommendations for lipid-lowering and antithrombotic therapy will improve the morbidity and mortality in patients with PAD.

An 18 year data-linkage study on the association between air pollution and acute limb ischaemia.

Background: There is limited information regarding the effects of air pollutants, such as nitrogen oxides (NOx), nitric oxide (NO2), nitrous oxide (NO) and particulate matter with a diameter smaller than 10 µm (PM10), on acute limb ischaemia (ALI), a peripheral arterial disease (PAD) often with a poor clinical outcome. Patients and methods: We conducted an 18-year retrospective cohort study using routinely collected healthcare records from Ninewells Hospital, Dundee, and Perth Royal Infirmary, in Tayside, Scotland, UK from 2000 to 2017. ALI hospitalisation events and deaths were linked to daily NOx, NO2, NO and PM10 levels extracted from publicly available data over this same time period. Distributed lag models were used to estimate risk ratios for ALI hospitalisation and for ALI mortality, adjusting for temperature, humidity, day of the week, month and public holiday. Results: 5,608 hospital admissions in 2,697 patients were identified over the study period (mean age 71.2 years, ±11.1). NOx and NO were associated with an increase of ALI hospital admissions on days of exposure to pollutant (p=.018), while PM10 was associated with a cumulative (lag 0-9 days) increase (p=.027) of ALI hospital admissions in our study. There was no increase of ALI mortality associated with pollution levels. Conclusions: ALI hospital admissions were positively associated with ambient NOx and NO on day of high measured pollution levels and a cumulative effect was seen with PM10.

Mitogen and Stress-Activated Kinases 1 and 2 Mediate Endothelial Dysfunction.

Inflammation promotes endothelial dysfunction, but the underlying mechanisms remain poorly defined in vivo. Using translational vascular function testing in myocardial infarction patients, a situation where inflammation is prevalent, and knock-out (KO) mouse models we demonstrate a role for mitogen-activated-protein-kinases (MAPKs) in endothelial dysfunction. Myocardial infarction significantly lowers mitogen and stress kinase 1/2 (MSK1/2) expression in peripheral blood mononuclear cells and diminished endothelial function. To further understand the role of MSK1/2 in vascular function we developed in vivo animal models to assess vascular responses to vasoactive drugs using laser Doppler imaging. Genetic deficiency of MSK1/2 in mice increased plasma levels of pro-inflammatory cytokines and promoted endothelial dysfunction, through attenuated production of nitric oxide (NO), which were further exacerbated by cholesterol feeding. MSK1/2 are activated by toll-like receptors through MyD88. MyD88 KO mice showed preserved endothelial function and reduced plasma cytokine expression, despite significant hypercholesterolemia. MSK1/2 kinases interact with MAPK-activated proteins 2/3 (MAPKAP2/3), which limit cytokine synthesis. Cholesterol-fed MAPKAP2/3 KO mice showed reduced plasma cytokine expression and preservation of endothelial function. MSK1/2 plays a significant role in the development of endothelial dysfunction and may provide a novel target for intervention to reduce vascular inflammation. Activation of MSK1/2 could reduce pro-inflammatory responses and preserve endothelial vasodilator function before development of significant vascular disease.

Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts: the BiomarCaRE project.

BACKGROUND: Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts. METHODS: The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality. RESULTS: The overall prevalence of CKD stage 3-5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts. CONCLUSION: CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.

Morbidity and mortality associated with atherosclerotic peripheral artery disease: A systematic review.

BACKGROUND AND AIMS: It is unclear whether improvements in the detection/treatment of peripheral artery disease (PAD) affect overall survival and morbidity. We undertook a systematic review to describe survival and morbidity in contemporary PAD cohorts. METHODS: Electronic databases were searched for randomised and observational studies reporting mortality/morbidity events between 1 May 2003 and 31 December, 2017 in patients with PAD, diagnosed by intermittent claudication (IC), critical limb ischaemia (CLI), or an ankle brachial index (ABI) < 0.9. Pooled event rates for all-cause and cardiovascular (CV) mortality, non-fatal myocardial infarction (MI), non-fatal stroke, major CV events (MACE; non-fatal MI/stroke, CV death), and major amputation were calculated per 1000 person-years. RESULTS: 124 eligible studies were identified (570,856 patients; 855,894 person-years of follow-up). Statin use was reported in 67% of the overall cohort and antiplatelet use in 79%. Pooled event rates for all-cause and CV mortality, MI, stroke, MACE, and major amputation were 113, 39, 20, 12, 71, and 70 per 1000 person-years, respectively. Compared with patients with an ABI <0.9, the presence of CLI was associated with increased rates of all-cause and CV mortality, MI, MACE, and major amputation. Event rates for stroke were similar between patients with an ABI <0.9 and CLI. CONCLUSIONS: Our data show PAD patients have a high risk of all-cause and CV mortality, and imply the risk of stroke or MI is at least equivalent to the risk in patients with coronary artery disease. Moreover, our data underline the need for improved treatments to attenuate CV risk in PAD patients.

A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. METHODS: A randomized, double-blind, placebo-controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P < 0.05. RA patients age >50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. RESULTS: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient-years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low-density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C-reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI -14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. CONCLUSION: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists' Collaboration meta-analysis of statin effects in other populations.

Prevalence and Distribution of Atherosclerosis in a Low- to Intermediate-Risk Population: Assessment with Whole-Body MR Angiography.

Purpose To quantify the burden and distribution of asymptomatic atherosclerosis in a population with a low to intermediate risk of cardiovascular disease. Materials and Methods Between June 2008 and February 2013, 1528 participants with 10-year risk of cardiovascular disease less than 20% were prospectively enrolled. They underwent whole-body magnetic resonance (MR) angiography at 3.0 T by using a two-injection, four-station acquisition technique. Thirty-one arterial segments were scored according to maximum stenosis. Scores were summed and normalized for the number of assessable arterial segments to provide a standardized atheroma score (SAS). Multiple linear regression was performed to assess effects of risk factors on atheroma burden. Results A total of 1513 participants (577 [37.9%] men; median age, 53.5 years; range, 40-83 years) completed the study protocol. Among 46 903 potentially analyzable segments, 46 601 (99.4%) were interpretable. Among these, 2468 segments (5%) demonstrated stenoses, of which 1649 (3.5%) showed stenosis less than 50% and 484 (1.0%) showed stenosis greater than or equal to 50%. Vascular stenoses were distributed throughout the body with no localized distribution. Seven hundred forty-seven (49.4%) participants had at least one stenotic vessel, and 408 (27.0%) participants had multiple stenotic vessels. At multivariable linear regression, SAS correlated with age (B = 3.4; 95% confidence interval: 2.61, 4.20), heart rate (B = 1.23; 95% confidence interval: 0.51, 1.95), systolic blood pressure (B = 0.02; 95% confidence interval: 0.01, 0.03), smoking status (B = 0.79; 95% confidence interval: 0.44, 1.15), and socioeconomic status (B = -0.06; 95% confidence interval: -0.10, -0.02) (P < .01 for all). Conclusion Whole-body MR angiography identifies early vascular disease at a population level. Although disease prevalence is low on a per-vessel level, vascular disease is common on a per-participant level, even in this low- to intermediate-risk cohort. © RSNA, 2018 Online supplemental material is available for this article.

Epicardial adipose tissue is related to arterial stiffness and inflammation in patients with cardiovascular disease and type 2 diabetes.

BACKGROUND: Epicardial adipose tissue (EAT) is an emerging cardio-metabolic risk factor and has been shown to correlate with adverse cardiovascular (CV) outcome; however the underlying pathophysiology of this link is not well understood. The aim of this study was to evaluate the relationship between EAT and a comprehensive panel of cardiovascular risk biomarkers and pulse wave velocity (PWV) and indexed left ventricular mass (LVMI) in a cohort of patients with cardiovascular disease (CVD) and diabetes compared to controls. METHODS: One hundred forty-five participants (mean age 63.9 ± 8.1 years; 61% male) were evaluated. All patients underwent cardiovascular magnetic resonance (CMR) examination and PWV. EAT measurements from CMR were performed on the 4-chamber view. Blood samples were taken and a range of CV biomarkers was evaluated. RESULTS: EAT measurements were significantly higher in the groups with CVD, with or without T2DM compared to patients without CVD or T2DM (group 1 EAT 15.9 ± 5.5 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, p = 0.001; group 3 EAT 15.1 ± 4.3 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, p = 0.024). EAT was independently associated with IL-6 (beta 0.2, p = 0.019). When added to clinical variables, both EAT (beta 0.16, p = 0.035) and IL-6 (beta 0.26, p = 0.003) were independently associated with PWV. EAT was significantly associated with LVMI in a univariable analysis but not when added to significant clinical variables. CONCLUSIONS: In patients with cardio-metabolic disease, EAT was independently associated with PWV. EAT may be associated with CVD risk due to an increase in systemic vascular inflammation. Whether targeting EAT may reduce inflammation and/or cardiovascular risk should be evaluated in prospective studies.

Systemic arteriosclerosis is associated with left ventricular remodeling but not atherosclerosis: a TASCFORCE study.

BACKGROUND: Arteriosclerosis (arterial stiffening) is associated with future cardiovascular events, with this effect postulated to be due to its effect on cardiac afterload, atherosclerosis (plaque formation) progression or both, but with limited evidence examining these early in disease formation. The aim of the current study is to examine the association between arteriosclerosis, atherosclerosis and ventricular remodelling in a population at low-intermediate cardiovascular risk. METHODS: One thousand six hundred fifty-one subjects free of clinical cardiovascular disease and with a < 20% 10 year cardiovascular risk score underwent a cardiovascular magnetic resonance (CMR) study and whole body CMR angiogram. Arteriosclerosis was measured using total arterial compliance (TAC) - calculated as the indexed stroke volume divided by the pulse pressure. Atherosclerosis was quantified using a standardised atheroma score (SAS) which was calculated by scoring 30 arterial segments within the body based on the degree of stenosis, summating these scores and normalising it to the number of assessable segments. Left ventricular remodelling was measured using left ventricular mass to volume ratio (LVMVR). RESULTS: One thousand five hundred fifteen (38% male, 53.8 ± 8.2 years old) completed the study. On univariate analysis TAC was associated with SAS but this was lost after accounting for cardiovascular risk factors in both males (B = - 0.001 (- 0.004-0.002),p = 0.62) and females (B = 0.000(95%CI -0.002--0.002),p = 0.78). In contrast compliance correlated with LVMVR after accounting for cardiovascular risk factors (B = - 0.12(95%CI -0.16--0.091),p < 0.001 in males; B = - 0.12(95%CI -0.15--0.086),p < 0.001 in females). CONCLUSION: Systemic arteriosclerosis is associated with left ventricular remodelling but not atherosclerosis. Future efforts in cardiovascular risk prevention should thus seek to address both arteriosclerosis and atherosclerosis individually.

Twenty-Year Predictors of Peripheral Arterial Disease Compared With Coronary Heart Disease in the Scottish Heart Health Extended Cohort (SHHEC).

BACKGROUND: Coronary heart disease and peripheral arterial disease (PAD) affect different vascular territories. Supplementing baseline findings with assays from stored serum, we compared their 20-year predictors. METHODS AND RESULTS: We randomly recruited 15 737 disease-free men and women aged 30 to 75 years across Scotland between 1984 and 1995 and followed them through 2009 for death and hospital diagnoses. Of these, 3098 developed coronary heart disease (19.7%), and 499 PAD (3.2%). Hazard ratios for 45 variables in the Cox model were adjusted for age and sex and for factors in the 2007 ASSIGN cardiovascular risk score. Forty-four of them were entered into parsimonious predictive models, tested by c-statistics and net reclassification improvements. Many hazard ratios diminished with adjustment and parsimonious modeling, leaving significant survivors. The hazard ratios were mostly higher in PAD. New parsimonious models increased the c-statistic and net reclassification improvements over ASSIGN variables alone but varied in their components and ranking. Coronary heart disease and PAD shared 7 of the 9 factors from ASSIGN: age, sex, family history, socioeconomic status, diabetes mellitus, tobacco smoking, and systolic blood pressure (but neither total nor high-density lipoprotein cholesterol); plus 4 new ones: NT-pro-BNP, cotinine, high-sensitivity C-reactive protein, and cystatin-C. The highest ranked hazard ratios for continuous factors in coronary heart disease were those for age, total cholesterol, high-sensitivity troponin, NT-pro-BNP, cotinine, apolipoprotein A, and waist circumference (plus 10 more); in PAD they were age, high-sensitivity C-reactive protein, systolic blood pressure, expired carbon monoxide, cotinine, socioeconomic status, and lipoprotein (a) (plus 5 more). CONCLUSIONS: The mixture of shared with disparate determinants for arterial disease in the heart and the legs implies nonidentical pathogenesis: cholesterol dominant in the former, and inflammation (high-sensitivity C-reactive protein, diabetes mellitus, smoking) in the latter.

Prevalence of unrecognized myocardial infarction in a low-intermediate risk asymptomatic cohort and its relation to systemic atherosclerosis.

AIMS: Unrecognized myocardial infarctions (UMIs) have been described in 19-30% of the general population using late gadolinium enhancement (LGE) on cardiac magnetic resonance. However, these studies have focused on an unselected cohort including those with known cardiovascular disease (CVD). The aim of the current study was to ascertain the prevalence of UMIs in a non-high-risk population using magnetic resonance imaging (MRI). METHODS AND RESULTS: A total of 5000 volunteers aged >40 years with no history of CVD and a 10-year risk of CVD of <20%, as assessed by the ATP-III risk score, were recruited to the Tayside Screening for Cardiac Events study. Those with a B-type natriuretic peptide (BNP) level greater than their gender-specific median were invited for a whole-body MR angiogram and cardiac MR including LGE assessment. LGE was classed as absent, UMI, or non-specific. A total of 1529 volunteers completed the imaging study; of these, 53 (3.6%) were excluded because of either missing data or inadequate LGE image quality. Ten of the remaining 1476 (0.67%) displayed LGE. Of these, three (0.2%) were consistent with UMI, whereas seven were non-specific occurring in the mid-myocardium (n = 4), epicardium (n = 1), or right ventricular insertion points (n = 2). Those with UMI had a significantly higher BNP [median 116 (range 31-133) vs. 22.6 (5-175) pg/mL, P = 0.015], lower ejection fraction [54.6 (36-62) vs. 68.9 (38-89)%, P = 0.007], and larger end-systolic volume [36.3 (27-61) vs. 21.7 (5-65) mL/m2, P = 0.014]. Those with non-specific LGE had lower diastolic blood pressure [68 (54-70) vs. 72 (46-98) mmHg, P = 0.013] but no differences in their cardiac function. CONCLUSION: Despite previous reports describing high prevalence of UMI in older populations, in a predominantly middle-aged cohort, those who are of intermediate or low cardiovascular risk have a very low risk of having an unrecognized myocardial infarct.