The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

Improved metabolic fitness, but no cardiovascular health effects, of a low-frequency short-term combined exercise programme in 50-70-year-olds with low fitness: A randomized controlled trial.

We evaluated the cardiometabolic effects of a 15-week combined exercise programme, implemented in sports clubs, for 50-70-year-olds with low aerobic fitness. In a randomized controlled trial, 45 participants (26 women) with low fitness were randomly assigned (2:1-ratio) to a training group (TG, n = 30) or inactive control group (CG, n = 15). TG had 15 weeks with one weekly 90-min supervised group-based session in a recreational sports club with combined aerobic exercise and strength training and were encouraged to perform home-based training 30 min/wk. Evaluations of relative VO2max (mLO2/min/kg), blood pressure, resting heart rate (HR), echocardiography, peripheral arterial tonometry, body composition, lipid profile and HbA1c were performed at 0 and 15 wks. Average HR during supervised training was 113 ± 13 bpm (68.6 ± 7.0%HRmax), with 4.3 ± 6.6% spent >90%HRmax. At 15-wk follow-up, intention-to-treat analyses revealed no between-group difference for VO2max/kg (0.4 mLO2/min/kg, 95%CI -0.8-1.5, P = 0.519; -3 mL/min, 95%CI -123-118, P = 0.966) or other cardiovascular outcomes (all P > 0.05). Compared to CG, total fat mass (-1.9 kg; 95%CI -3.2 to -0.5, P = 0.005), total fat percentage (-1.3%, 95%CI -2.2 to -0.3, P = 0.01) and total/HDL cholesterol ratio (P = 0.032) decreased in TG. Regular adherence to supervised training was high (81%), but 0% for home-based exercise. In conclusion, the group-based supervised training was associated with high adherence and moderate exercise intensity, whereas insufficiently supported home-based training was not feasible. Together, 15 wks of combined exercise training did not improve aerobic fitness or affected cardiovascular function in 50-70-yr-olds with low aerobic fitness, whereas some positive effects were observed in metabolic parameters.Highlights Combined exercise training implemented in a sports club elicited moderate aerobic intensity in 50-70-year-old untrained individuals.Supervised group-based training had high adherence whereas unsupported home-based training had very low adherence.15 weeks of low-frequency combined moderate intensity exercise training improved lipid profile and fat mass, but had no effect on cardiovascular fitness.

Importance of Risk Assessment in Timing of Invasive Coronary Evaluation and Treatment of Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome: Insights From the VERDICT Trial.

Background The optimal timing of invasive examination and treatment of high-risk patients with non-ST-segment-elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard-care invasive coronary angiography on the risk of all-cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non-ST-segment-elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48-72 hours) invasive strategy. The primary outcome of the present study was all-cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow-up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16-3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63-1.10]) (Pinteraction=0.006). Conclusions In patients with non-ST-segment-elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high-risk and low-risk patients with non-ST-segment-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02061891.

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Myocardial CT perfusion compared with transthoracic Doppler echocardiography in evaluation of the coronary microvascular function: An iPOWER substudy.

BACKGROUND: A significant number of women with angina and no obstructive coronary artery disease (CAD; <50% stenosis) have coronary microvascular dysfunction (CMD) which carries an adverse cardiovascular prognosis. Coronary microvascular function can be evaluated by transthoracic Doppler echocardiography (TTDE) as a coronary flow velocity reserve (CFVR) and by static CT myocardial perfusion (CTP) as a myocardial perfusion reserve (MPR). Whether these methods are correlated is not known. We assessed the correlation between CFVR and MPR and investigated whether women with angina, CMD and no obstructive CAD have reduced MPR compared with asymptomatic women. METHODS: Static CTP with adenosine-induced vasodilation and TTDE of the left anterior descending artery with dipyridamole-induced vasodilation were successfully performed and analysed in 99 women with stable angina and no obstructive CAD and 33 asymptomatic women with no obstructive CAD. CMD was defined as CFVR < 2. RESULTS: Correlation between rate-pressure product corrected MPR and CFVR was weak but significant (r = .23; p = .007). MPR was highest among asymptomatic women with normal CFVR (median [interquartile range; IQR] 158 [145-181] %). Symptomatic women with normal CFVR had reduced MPR (148 [134-162] %; age-adjusted p < .001); however, the lowest MPR was found in symptomatic women with CMD (140 [129-164] %; age-adjusted p < .001), independent of cardiovascular risk factors and haemodynamic parameters (p = .017). CONCLUSION: Women with angina, CMD and no obstructive CAD had markedly diminished MPR compared with asymptomatic women. Correlation between CFVR and MPR was weak, suggesting that CTP and TTDE are not interchangeable for detection of CMD.

Resilience of HPV vaccine uptake in Denmark: Decline and recovery.

BACKGROUND: Immunization programs' resilience to shocks is central to their success, but little empirical evidence documents resilience in action. We sought to characterize the decline of HPV vaccination in Denmark after negative media coverage and recovery during a national information campaign. METHODS: We conducted a population-based retrospective cohort study of all girls born in Denmark from 1997 to 2006 (N = 328,779), aged 12-15. The outcome measure was HPV vaccine uptake (first dose), as reported to the Danish national health registry from 2009 to 2019, when HPV vaccine was freely available to girls in primary care clinics in Denmark. Events that created 4 natural time periods for study were HPV vaccine reaching the uptake of other vaccines in the national program (2009), some negative media coverage of HPV vaccination (2013), extensive negative media coverage (2015), and a national information campaign about the vaccine's safety and effectiveness (2017-2019). RESULTS: In the period with some negative media coverage, HPV vaccine uptake fell to 83.6% (95% CI:78.0%-89.7%) of baseline uptake. In the period with extensive negative media coverage, uptake fell even further to 49.6% (95% CI:44.5%-55.2%) of baseline uptake. After the information campaign, HPV vaccine uptake recovered to its baseline level (109.2%, 95% CI:90.1%-132.4%) due in part to catch-up doses. Despite the recovery, an estimated 26,000 fewer girls initiated the vaccine than if uptake had not declined. CONCLUSIONS: The experience in Denmark offers one of the first opportunities to document how a nation grappled with negative media coverage of HPV vaccination and the steadying impact of action by national authorities.

Feasibility and Health Effects of a 15-Week Combined Exercise Programme for Sedentary Elderly: A Randomised Controlled Trial.

There is strong evidence that considerable health benefits can be achieved even with small amounts of physical activity. However, getting people to exercise regularly is a major challenge not least in the elderly population. This study investigated the feasibility and physiological health effects of a pragmatic 15-week exercise programme for sedentary elderly. In a single-blind randomised controlled trial, 45 sedentary 60-83-year-olds (25 women, 20 men) were randomly assigned (2:1 ratio) to a training group (TG, n=30) or a control group (CG, n=15). The training in TG consisted of a combination of exercise modalities (i.e., strength, aerobic fitness, stability, and flexibility training) performed once a week as supervised group-based training and a weekly home-based training for 15 weeks. Feasibility outcomes were exercise intensity, adherence, and adverse events. The primary outcome was change in aerobic fitness (VO2max/kg). Adherence was high (81%) for the supervised exercise and low (0%) for the home-based exercise. No acute injuries occurred in TG, but 4 subjects (13%) reported considerable joint pain related to training. Average heart rate (HR) during the supervised training was 104±12 beats/min (69.3±8.0%HRmax), with 3.9±7.3% of training time >90%HRmax. Intention-to-treat analyses revealed no between-group differences for aerobic fitness (P=0.790) or any secondary cardiovascular outcomes at 15-week follow-up (resting HR or blood pressure; P>0.05). Compared to CG, bodyweight (-2.3 kg, 95% CI -4.0 to -7.0; P=0.006), total fat mass (-2.0 kg, 95% CI -3.5 to -0.5; P=0.01), and total fat percentage (-1.6%, 95% CI -2.8 to -0.3; P=0.01) decreased in TG. The group-based supervised training had high adherence and moderate exercise intensity, whereas the home-based training was not feasible in this study population. This exercise programme performed once a week did not improve aerobic fitness. Thus, supervised training with more vigorous intensity control appears advisable. Clinical Study registration number is H-15016951.

Prognostic role of genetic polymorphisms of the interleukin-6 signaling pathway in patients with severe heart failure.

Heart failure (HF) is associated with perturbations of the interleukin-6 (IL-6) signaling pathway. A total of 559 Danish subjects with severe chronic HF enrolled in the previously reported Echocardiography and Heart Outcome Study were genotyped for three SNPs in IL6, nine in the IL-6 receptor gene (IL6R), and two in the IL-6 signal transducer gene (IL6ST). After a mean follow-up of 5.0 years, 5 SNPs in IL6R introns (rs12083537, rs6684439, rs4845622, rs4537545, and rs7529229) and a SNP in the IL6R coding region (rs2228145, also known as Asp358Ala) were associated with adverse outcomes, e.g., hazard ratios (HRs) for cardiovascular death and all-cause death 1.38 (CI: 1.09-1.76; P = 0.008) and 1.37 (CI: 1.10-1.70; P = 0.004) for rs6684439 heterozygotes, and 1.39 (CI: 1.09-1.77; P = 0.007) and 1.37 (CI: 1.10-1.70; P = 0.005) for rs4845622 heterozygotes, respectively. We conclude that SNPs in the IL-6 signaling pathway may be independent predictors of fatal outcomes in patients with severe HF.

Ten-year clinical outcome of patients treated with a drug-eluting stent in the proximal left anterior descending artery segment compared with patients stented in other non-left main coronary segments.

AIMS: The aim of the study was to determine whether patients treated with drug-eluting stents in the proximal left anterior descending artery (LAD) carried a different long-term prognosis from patients treated in other coronary artery segments. METHODS AND RESULTS: Ten-year clinical outcome expressed as all-cause mortality and major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, or target vessel revascularisation) was determined for 1,479 patients with a single non-left main coronary stenosis treated with a first-generation drug-eluting stent in the SORT OUT II trial. The outcome of patients treated with stents in the proximal LAD (n=365) was compared with that of patients treated in a non-proximal LAD segment (n=1,114). Follow-up was 99.3% complete. All-cause mortality was 24.9% in the proximal LAD group vs. 26.3% in the non-proximal LAD group (p=0.60). MACE occurred less frequently in the proximal LAD group, 24.6% vs. 31.0% with a hazard ratio of 0.77 (95% confidence interval [CI]: 0.61-0.97, p=0.024). After multivariate analysis which included baseline characteristics that were unevenly distributed between the groups, the hazard ratio for MACE was 0.82 (95% CI: 0.65-1.03, p=0.09). CONCLUSIONS: Patients treated with a drug-eluting stent in the proximal LAD have similar, if not better, long-term clinical outcome compared with patients stented in other coronary artery segments.

Imiquimod-Induced Psoriasis-Like Skin Lesions Do Not Accelerate Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice.

Psoriasis is a chronic inflammatory skin disorder associated with several comorbidities, including atherosclerosis. Disease mechanisms that may affect both psoriasis and atherosclerosis include activation of T helper 1 and T helper 17 cells. Imiquimod application is an established mouse model of psoriasis-like skin inflammation. The cardiac glycoside digoxin inhibits the master transcription factor of T helper 17 differentiation, retinoid acid receptor-related orphan nuclear receptor γt, and attenuates IL-17-dependent pathologies in mice. We investigated whether cyclic imiquimod-induced psoriasis-like skin inflammation affects atherosclerosis in low-density lipoprotein receptor-deficient mice and whether digoxin modifies either disease. Topical imiquimod application increased ear thickness, keratinocyte proliferation, and accumulation of CD3+ T cells in the skin of low-density lipoprotein receptor-deficient mice. Also, imiquimod affected the mice systemically with induction of splenomegaly as well as increased plasma levels of IL-17A and serum amyloid A. Overall, imiquimod reduced atherosclerosis in the aortic arch en face, but it did not affect atherosclerosis in the aortic root. Digoxin significantly reduced the imiquimod-induced ear thickening, had divergent effects on imiquimod-induced systemic inflammation, and did not affect atherosclerosis. In conclusion, cyclic imiquimod applications can be used for long-term induction of psoriasis-like skin lesions, but they attenuate atherosclerosis in low-density lipoprotein-deficient mice. In this model, digoxin reduces skin inflammation, but it has no effect on atherosclerosis.

Incident Heart Failure in Patients With Rheumatoid Arthritis: A Nationwide Cohort Study.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with a wide range of comorbidities, including cardiovascular disease, but its association with heart failure (HF) is not fully clear. We investigated the risk of incident HF in a nationwide cohort of patients with RA. METHODS AND RESULTS: The study comprised the entire Danish population aged ≥18 years followed from January 1, 2008 until first hospitalization for HF, emigration, December 31, 2012, or death. Information on comorbidity, medication, and socioeconomic status was identified by individual-level linkage of administrative registers. Patients with a rheumatologist diagnosis of RA between 1978 and 2008 were included. The primary study outcome was incident HF defined as first hospital admission for HF. Incidence rates of HF per 1000 person-years were calculated and incidence rate ratios adjusted for age, sex, calendar year, comorbidity, medications, socioeconomic status, smoking, and alcohol consumption were estimated. A total of 4 305 225 subjects with no history of HF were eligible for analysis at the study start. Of these subjects, 24 343 developed RA and 50 623 were hospitalized for HF. Overall incidence rates of incident HF were 2.43 and 6.64 for the reference population (n=49 879) and patients with RA (n=744), respectively. Correspondingly, the fully adjusted incidence rate ratio for incident HF was increased in patients with RA with incidence rate ratio 1.30 (95% confidence interval, 1.17-1.45). CONCLUSIONS: In this cohort study, RA was associated with an increased hospitalization for HF. These findings add significantly to the existing evidence of RA as a clinically relevant risk factor for HF.

Ventricular repolarization alterations in women with angina pectoris and suspected coronary microvascular dysfunction.

OBJECTIVES: CMD could be the explanation of angina pectoris with no obstructive CAD and may cause ventricular repolarization changes. We compared T-wave morphology and QTc interval in women with angina pectoris with a control group as well as the associations with CMD. METHODS: Women with angina pectoris and no obstructive coronary artery disease (n=138) and age-matched controls were compared in regard to QTc interval and morphology combination score (MCS) based on T-wave asymmetry, flatness and presence of T-wave notch. CMD was assessed as a coronary flow velocity reserve (CFVR) by transthoracic echocardiography. RESULTS: Women with angina pectoris had significantly longer QTc intervals (429±20ms) and increased MCS (IQR) (0.73 [0.64-0.80]) compared with the controls (419±20ms) and (0.63 [(0.53-0.73]), respectively (both p<0.001). CFVR was associated with longer QTc interval (p=0.02), but the association was attenuated after multivariable adjustment (p=0.08). CONCLUSION: This study suggests that women with angina pectoris have alterations in T-wave morphology as well as longer QTc interval compared with a reference population. CMD might be an explanation.

Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy following alcohol septal ablation.

Aims: The HCM Risk-SCD model for prediction of sudden cardiac death (SCD) in hypertrophic cardiomyopathy recommended by the 2014 European Society of Cardiology (ESC) guidelines has not been validated after septal reduction therapy. The aim of this study was to validate the HCM Risk-SCD model in patients undergoing alcohol septal ablation (ASA) and to compare its performance to previous models. Methods and result: A total of 844 ASA patients without prior SCD event were included. The primary endpoint was a composite of SCD and appropriate implantable cardioverter defibrillator (ICD) therapy, identical to the HCM Risk-SCD endpoint. A distinction between periprocedural (≤30 days) and long-term (>30 days) SCD was made to discern procedure-related adverse arrhythmic events caused by the ASA-induced myocardial infarction from long-term SCD risk. Twenty patients reached the SCD endpoint within the first 30 days. During a follow-up of 6.5 ± 4.2 years, another 46 patients reached the SCD endpoint. The predicted 5-year SCD risk according to the HCM Risk-SCD model was 5.1%, and the observed 5-year SCD risk was 4.0%. The C-statistics for the use of the HCM Risk-SCD model was 0.61 (P = 0.02), the C-statistics for the use of the 2003 American College of Cardiology/ESC guidelines was 0.59 (P = 0.051), and the C-statistic for the use of the 2011 American College of Cardiology Foundation/American Heart Association guidelines was 0.58 (P = 0.054). Maximal left ventricular wall thickness, syncope after ASA, and fulfilling the 2014 ESC recommendations for primary ICD implantation according to the HCM Risk-SCD model, respectively, predicted SCD during long-term follow-up. Conclusion: The HCM Risk-SCD model can be used for SCD prediction in patients undergoing ASA.

Effects of recreational football on women's fitness and health: adaptations and mechanisms.

The review describes the fitness and health effects of recreational football in women aged 18-65 years. The review documents that 2 × 1 h of recreational football training for 12-16 weeks causes marked improvements in maximal oxygen uptake (5-15%) and myocardial function in women. Moreover, mean arterial blood pressure was shown to decrease by 2-5 mmHg in normotensive women and 6-8 mmHg in hypertensive women. This review also show that short-term (< 4 months) and medium-term (4-16 months) recreational football training has major beneficial impact on metabolic health profile in women, with fat losses of 1-3 kg and improvements in blood lipid profile. Lastly, 2 × 1 h per week of recreational football training for women elevates lower extremity bone mineralisation by 1-5% and whole-body bone mineralization by 1-2% within 4-12-month interventions. These training adaptations are related to the high heart rates, high number of fast runs, and multiple changes of direction and speed occurring during recreational football training for untrained women. In conclusion, regular small-sided football training for women is an intense and versatile type of training that combines elements of high-intensity interval training (HIIT), endurance training and strength training, thereby providing optimal stimuli for cardiovascular, metabolic and musculoskeletal fitness. Recreational football, therefore, seems to be an effective tool for prevention and treatment of lifestyle diseases in young and middle-aged women, including hypertension, type 2 diabetes and osteopenia. Future research should elucidate effects of football training for elderly women, and as treatment and rehabilitation of breast cancer patients and other women patient groups.

Coronary microvascular dysfunction and myocardial contractile reserve in women with angina and no obstructive coronary artery disease.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a potential cause of myocardial ischemia and may affect myocardial function at rest and during stress. We investigated whether CMD was associated with left ventricular diastolic and systolic function at rest and during pharmacologically induced hyperemic stress. METHODS: In a prospective cohort study, we included 963 women with angina, left ventricular ejection fraction (LVEF) >45%, and an invasive coronary angiogram without significant stenosis (<50%). Parameters of left ventricular diastolic function, LVEF, speckle tracking-derived global longitudinal strain (GLS), and coronary flow velocity reserve (CFVR) were assessed by transthoracic echocardiography at rest and during dipyridamole stress. The GLS and LVEF reserves were defined as the absolute increases in GLS and LVEF during stress. RESULTS: Coronary flow velocity reserve (CFVR) was measured in 919 women of whom 26% had CMD (defined as CFVR < 2). Coronary microvascular dysfunction (CMD) was associated with higher age and a higher resting heart rate. Women with CMD had a reduced GLS reserve (P = .005), while we found no association between CFVR and LVEF at rest, GLS at rest, or the LVEF reserve, respectively. Global longitudinal strain (GLS) reserve remained associated with CFVR (P = .002) in a multivariable regression analysis adjusted for age, hemodynamic variables, and GLS at rest. In age-adjusted analysis, women with low CFVR had no signs of left ventricular diastolic dysfunction measured by echocardiography at rest. CONCLUSION: The GLS reserve was significantly lower in women with CMD. The mechanisms underlying the association between CMD and GLS reserve warrant further study.

Return to Work and Risk of Subsequent Detachment From Employment After Myocardial Infarction: Insights From Danish Nationwide Registries.

BACKGROUND: Limited data are available on return to work and subsequent detachment from employment after admission for myocardial infarction (MI). METHODS AND RESULTS: Using individual-level linkage of data from nationwide registries, we identified patients of working age (30-65 years) discharged after first-time MI in the period 1997 to 2012, who were employed before admission. To assess the cumulative incidence of return to work and detachment from employment, the Aalen Johansen estimator was used. Incidences were compared with population controls matched on age and sex. Logistic regression was applied to estimate odds ratios for associations between detachment from employment and age, sex, comorbidities, income, and education level. Of 39 296 patients of working age discharged after first-time MI, 22 394 (56.9%) were employed before admission. Within 1 year 91.1% (95% confidence interval [CI], 90.7%-91.5%) of subjects had returned to work, but 1 year after their return 24.2% (95% CI, 23.6%-24.8%) were detached from employment and received social benefits. Detachment rates were highest in patients aged 60 to 65 and 30 to 39 years, and significantly higher in patients with MI compared with population controls. Predictors of detachment were heart failure (odds ratio 1.20 [95% CI, 1.08-1.34]), diabetes mellitus (odds ratio 1.13 [95% CI, 1.01-1.25]), and depression (odds ratio 1.77 [95% CI, 1.55-2.01]). High education level and high income favored continued employment. CONCLUSIONS: Despite that most patients returned to work after first-time MI, about 1 in 4 was detached from employment after 1 year. Several factors including age and lower socioeconomic status were associated with risk of detachment from employment.