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Suspected myocardial infarction with non-obstructive coronary arteries (MINOCA) has received increasing attention over the past decade. Given the heterogeneity in the mechanisms underlying acute myocardial infarction in the absence of obstructive coronary arteries, the syndrome of MINOCA is considered a working diagnosis that requires further investigation after diagnostic angiography studies have been performed, including coronary magnetic resonance angiography and functional angiography. Although once considered an infrequent and low-risk form of myocardial infarction, recent data have shown that the prognosis of MINOCA is not as benign as previously assumed. However, despite increasing awareness of the condition, many questions remain regarding the diagnosis, risk stratification and treatment of MINOCA. Women seem to be more susceptible to MINOCA, but studies on the sex-specific differences of the disease are scarce. Similarly, ethnicity-specific factors might explain discrepancies in the observed prevalence or underlying pathophysiological mechanisms of MINOCA but data are also scarce. Therefore, in this Review, we provide an update on the latest evidence available on the sex-specific and ethnicity-specific differences in the clinical features, pathophysiological mechanisms, treatment and prognosis of MINOCA., (© 2023. Springer Nature Limited.)

Background: There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are at higher risk for the development of coronary artery disease (CAD) later in life. We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM, and risk of premature CAD (PCAD). Methods: This research project involved a data linkage approach merging three databases of South Australian cohorts by using a retrospective, age-matched case-control study design. Cases ( n  = 721) were ascertained from the Coronary Angiogram Database of South Australia (CADOSA). Women <60 years from CADOSA were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain their prior pregnancy outcomes. Controls ( n  = 194) were selected from North West Adelaide Health Study (NWAHS) and comprised women who were healthy or had other health conditions unrelated to CAD, age-matched to CADOSA (±5 years), and linked to SAPSC to determine their pregnancy outcomes. PCAD was defined as >50% stenosis in one or more coronary arteries at coronary angiography. Results: Compared with women without a history of PCAD, women who were diagnosed with PCAD were more likely to have experienced the placenta-mediated pregnancy complications of preterm birth (adjusted odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.21-5.00) or low-birth weight (adjusted OR = 2.44, 95% CI: 1.22-4.88), or have been diagnosed with active asthma during pregnancy (adjusted OR = 3.52, 95% CI: 1.05-11.76). Conclusion: Placenta-mediated pregnancy complications should be recognized as clear risk markers for future PCAD.

Background: We aimed to systematically examine literature on the prevalence of known modifiable and nonmodifiable risk factors for premature coronary heart disease (PCHD) in women compared with men. Materials and Methods: PubMed, CINAHL, Embase, and Web of Science databases were searched. Review protocol is registered in PROSPERO (CRD42020173216). Quality was assessed using the National Heart, Lung, and Blood Institute tool. Review Manager 5.3 was used for meta-analysis. Effect sizes were expressed as odds ratio (OR) and mean differences/standardized mean differences (SMD) with 95% confidence intervals (CIs) for categorical and continuous variables. Results: In this PCHD cohort (age <65 years), the mean age of presentation in women was 3 years older than men. Women had higher total cholesterol (SMD 0.11; 95% CI 0.00 to 0.23) and higher high-density lipoprotein cholesterol (SMD 0.49; 95% CI 0.29 to 0.69). Women were more likely to have hypertension (OR 1.51, 95% CI 1.42 to 1.60), diabetes mellitus (OR 1.78, 95% CI 1.55 to 2.04), obesity (OR 1.33, 95% CI 1.24 to 1.42), metabolic syndrome (OR 3.73, 95% CI 1.60 to 8.69), stroke (OR 1.63, 95% CI 1.51 to 1.77), peripheral vascular disorder (OR 1.67, 95% CI 1.43 to 1.96), and depression (OR 2.29, 95% CI 1.96 to 2.67). Women were less likely to be smokers (OR 0.60, 95% CI 0.55 to 0.66), have reported alcohol intake (OR 0.36, 95% CI 0.33 to 0.40), and reported use of illicit drug (OR 0.32, 95% CI 0.16 to 0.62). Conclusions: Risk factor profile in PCHD has a clear sex difference that supports early, aggressive, holistic, but sex-specific, approach to prevention.

Obstructive sleep apnoea (OSA) is increasingly recognized to be a risk factor for cardiovascular disease. This study assessed the prevalence and clinical predictors of OSA in patients undergoing coronary angiography. Consecutive patients undergoing coronary angiography in South Australian public hospitals from 2015 to 2018 were included. Clinical details for consecutive patients undergoing coronary angiography in South Australian public hospitals were captured by the Coronary Angiogram Database of South Australia (CADOSA) registry staff, with OSA identified by patient report. Among the 9,885 patients undergoing coronary angiography for the investigation of chest pain, 11% (n = 1,089) were documented as having OSA. Independent clinical predictors of OSA included male gender (OR 2.22, 1.86-2.65, P < 0.001), diabetes mellitus (OR 1.84, 1.58-2.14, P < 0.001), depression (OR 1.81, 1.55-2.12, P < 0.001), prior heart failure (OR 1.63, 1.22-2.18, P = 0.001), hypertension (OR 1.61, 1.32-1.95, P ≤ 0.001), asthma (OR 1.61, 1.34-1.93, P < 0.001), not a current smoker (OR 1.60, 1.30-1.96, P < 0.001), dyslipidaemia (OR 1.46, 1.22-1.76, P < 0.001), non-acute coronary syndrome presentation (OR 1.45, 1.25-1.69, P < 0.001), chronic lung disease (OR 1.40, 1.12-1.73, P = 0.003), cerebrovascular disease (OR 1.36, 1.07-1.73, P = 0.012), non-obstructive coronary artery disease (NOCAD) (OR 1.30, 1.10-1.55, P = 0.003) and atrial fibrillation/flutter (OR 1.30, 1.06-1.60, P = 0.012). Finally, stable angina (32.1% vs 22.7%) and NOCAD (29.1% vs 26.3%, P = 0.051) were trended more common in patients with OSA versus no OSA. In addition to established risk factors for OSA, this study found NOCAD to be independent predictor of OSA; especially in those presenting with a stable angina presentation. This suggests that coronary vasomotor disorders may be associated with OSA, although further detailed studies are required., (Copyright © 2021 Elsevier Inc. All rights reserved.)

PCAD possesses a public health challenge resulting in years of productive life lost and an escalating burden on health systems. Objective of this review is to compare modifiable and non-modifiable risk factors for PCAD compared to those without PCAD. This review will include all comparative observational studies conducted in adults aged >18 years with confirmed diagnosis of PCAD (on angiography) compared to those without PCAD. Databases to be searched include; PubMed, CINAHL, Embase, Web of Science, and grey literature (Google Scholar). All identified studies will be screened for title and abstract and full-text against the inclusion criteria on Covidence software. Data relevant to exposures and outcomes will be extracted from all included studies. All studies selected for data extraction will be critically appraised for methodological quality. Meta-analysis using random-effects model will be performed using Review Manager 5.3. Effect sizes for categorical risk factors will be expressed as odds ratios with 95% confidence intervals. For risk factors measured in continuous form, mean difference (if units are consistent) otherwise standardized mean difference (if units are different across studies) will be reported. Heterogeneity between studies will be assessed using I 2 test statistics. GRADE will be used to assess the certainty of the findings. Systematic review registration number: PROSPERO Registration # CRD42020173216., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Khoja A et al.)

Up to half of patients undergoing elective coronary angiography for the investigation of chest pain do not present with evidence of obstructive coronary artery disease. These patients are often discharged with a diagnosis of non-cardiac chest pain, yet many could have an ischaemic basis for their symptoms. This type of ischaemic chest pain in the absence of obstructive coronary artery disease is referred to as INOCA (ischaemia with non-obstructive coronary arteries). This comprehensive review of INOCA management looks at why these patients require treatment, who requires treatment based on diagnostic evaluation, what clinical treatment targets should be considered, how to treat patients using a personalised medicine approach, when to initiate treatment, and where future research is progressing., Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none. Provenance and peer review: Commissioned; externally peer reviewed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Suspected myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) occurs in ≈5% to 10% of patients with MI referred for coronary angiography. The prognosis of these patients may differ to those with MI and obstructive coronary artery disease (MI-CAD) and those without a MI (patients without known history of MI [No-MI]). The primary objective of this study is to evaluate the 12-month all-cause mortality of patients with MINOCA., Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the terms "MI," "nonobstructive," "angiography," and "prognosis" were searched in PubMed and Embase databases from inception to December 2018, including original, English language MINOCA studies with >100 consecutive patients. Publications with a heterogeneous cohort, unreported coronary stenosis, or exclusively focusing on MINOCA-mimicking conditions, were excluded. Unpublished data were obtained from the MINOCA Global Collaboration. Data were pooled and analyzed using Paule-Mandel, Hartung, Knapp, Sidik & Jonkman, or restricted maximum-likelihood random-effects meta-analysis methodology. Heterogeneity was assessed using Cochran's Q and I 2 statistics. The primary outcome was 12-month all-cause mortality in patients with MINOCA, with secondary comparisons to MI-CAD and No-MI., Results: The 23 eligible studies yielded 55 369 suspected MINOCA, 485 382 MI-CAD, and 33 074 No-MI. Pooled meta-analysis of 14 MINOCA studies accounting for 30 733 patients revealed an unadjusted 12-month all-cause mortality rate of 3.4% (95% CI, 2.6%-4.2%) and reinfarction (n=27 605; 10 studies) in 2.6% (95% CI, 1.7%-3.5%). MINOCA had a lower 12-month all-cause mortality than those with MI-CAD (3.3% [95% CI, 2.5%-4.1%] versus 5.6% [95% CI, 4.1%-7.0%]; odds ratio, 0.60 [95% CI, 0.52-0.70], P <0.001). In contrast, there was a statistically nonsignificant trend towards increased 12-month all-cause mortality in patients with MINOCA (2.6% [95% CI, 0%-5.9%]) compared with No-MI (0.7% [95% CI, 0.1%-1.3%]; odds ratio, 3.71 [95% CI, 0.58-23.61], P =0.09)., Conclusions: In the largest contemporary MINOCA meta-analysis to date, patients with suspected MINOCA had a favorable prognosis compared with MI-CAD, but statistically nonsignificant trend toward worse outcomes compared to those with No-MI. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42020145356.

Aims: The prognosis of patients with MINOCA (myocardial infarction with non-obstructive coronary arteries) is poorly understood. We examined major adverse cardiac events (MACE) defined as all-cause mortality, re-hospitalization for acute myocardial infarction (AMI), heart failure (HF), or stroke 12-months post-AMI in patients with MINOCA versus AMI patients with obstructive coronary artery disease (MICAD)., Methods and Results: Multicentre, observational cohort study of patients with AMI (≥65 years) from the National Cardiovascular Data Registry CathPCI Registry (July 2009-December 2013) who underwent coronary angiography with linkage to the Centers for Medicare and Medicaid (CMS) claims data. Patients were classified as MICAD or MINOCA by the presence or absence of an epicardial vessel with ≥50% stenosis. The primary endpoint was MACE at 12 months, and secondary endpoints included the components of MACE over 12 months. Among 286 780 AMI admissions (276 522 unique patients), 16 849 (5.9%) had MINOCA. The 12-month rates of MACE (18.7% vs. 27.6%), mortality (12.3% vs. 16.7%), and re-hospitalization for AMI (1.3% vs. 6.1%) and HF (5.9% vs. 9.3%) were significantly lower for MINOCA vs. MICAD patients (P < 0.001), but was similar between MINOCA and MICAD patients for re-hospitalization for stroke (1.6% vs. 1.4%, P = 0.128). Following risk-adjustment, MINOCA patients had a 43% lower risk of MACE over 12 months (hazard ratio = 0.57, 95% confidence interval 0.55-0.59), in comparison to MICAD patients. This pattern was similar for adjusted risks of the MACE components., Conclusion: This study confirms an unfavourable prognosis in elderly patients with MINOCA undergoing coronary angiography, with one in five patients with MINOCA suffering a major adverse event over 12 months., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Many studies have demonstrated the prevalence of depression in patients with coronary artery disease (CAD), but few have examined this relation in those with chest pain who do not have obstructive CAD on angiography. The aim of this study was to compare the prevalence of depression amongst patients with chest pain in the presence or absence of obstructive CAD and a healthy control group without chest pain. This prospectively designed, observational cohort study used 2 independent data sets: (1) The Queen Elizabeth Hospital Coronary Angiogram Database (n = 1,144), consisting of 819 patients with obstructive CAD and 325 patients with nonobstructive CAD (NoCAD), all of whom had chest pain and (2) the North West Adelaide Health Study (NWAHS; n = 3,168), a population-based biomedical cohort, from which patients with chest pain were excluded. The presence of depression was determined by a previously validated method using the Short Form 36. The prevalence of depression differed among the 3 groups, with 63% in those with NoCAD, 53% in those with CAD, and only 24% in the healthy NWAHS cohort. Analysis of the angiography cohort revealed age, gender, antidepressant medication, previous myocardial infarction, previous airway disease, Short Form 36 physical summary score, Seattle Angina Questionnaire physical limitation score, and NoCAD on angiography to be independent predictors of depression. In conclusion, these findings highlight the importance of screening for depression in patients with NoCAD., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Background: With our aging communities and the increased prevalence of coronary heart disease (CAD) with age, the impact of this disease in the very old warrants further investigation., Objective: To assess health outcomes and the attainment of guideline-based secondary prevention targets in the very old (>80 years, n=482) as compared to young (<65 years, n=582) and elderly (between 65 and 80 years, n=932) patients, all of whom had chronic stable angina., Design: The coronary artery disease in general practice (CADENCE) study was a cluster-stratified cross-sectional survey. This study reports on health outcomes quantitated using the Seattle Angina Questionnaire and guideline targets achieved for blood pressure, smoking, lipids, diabetic control and body habitus., Settings and Participants: 2031 stable angina patients were recruited from 207 primary care practices., Results: Despite similar angina frequency scores, the very old were more physically impaired by their angina than both the young and elderly [76±25 (Young) vs. 70±26 (Elderly) vs. 63±28 (Very old), p<0.05 for both comparisons]. However, the very old had better quality of life scores than young stable angina patients [72±24 vs. 65±25, p<0.05] and were similar to the elderly [72±24 vs. 72±23, p>0.05]. Also blood pressure, lipid, diabetic and body habitus targets were more often achieved in the very old and elderly patients compared to young stable angina patients., Conclusion: Despite similar symptomatic status and greater physical limitations, the very old reported a better quality of life and more often achieved treatment targets than young stable angina patients. Failure to improve secondary prevention measures in younger age groups may potentially contribute to increased morbidity in older age, and failure to achieve 'Healthy Ageing'., (Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Improvements in patient-reported health-related quality of life (HRQoL) are important goals of cardiac rehabilitation (CR). In patients undergoing coronary angiography for angina and with documented coronary artery disease (CAD), the present study compared HRQoL over 6 months in CR participants and non-participants. Clinical predictors of CR participants were also assessed., Methods: A total of 221 consecutive patients undergoing angiography for angina with documented CAD and who were eligible for a CR program were recruited. CR participants were enrolled in a six-week Phase II outpatient CR course (31%, n = 68) within 2 months following angiography and the non-participants were included as a control. At baseline (angiography), one and six months post angiography, clinical and HRQoL data were obtained including the Short Form-36 (SF-36) and the Seattle Angina Questionnaire (SAQ). The response rate for the HRQoL assessment was 68% (n = 150). Cross sectional comparisons were age-adjusted and performed using logistic or linear regression as appropriate. Longitudinal changes in HRQoL were assessed using least squares regression. Finally, a multiple logistic regression was fitted with CR participant as the final outcome., Results: At angiography, the CR non-participants were older, and age-adjusted analyses revealed poorer physical (angina limitation: 54 ± 25 versus 64 ± 22, p <0.05) and mental HRQoL (significant psycho-social distress: 62%, n = 95 versus 47%, n = 32, p <0.05) compared to the CR participants. In addition, the CR participants were more likely to have undergone angiography for myocardial infarction (OR = 2.8, 95% CI 1.5-5.3, p = 0.001). By six months, all patients showed an improvement in HRQoL indices, however the rate of improvement did not differ between the controls and CR participants., Conclusion: Following angiography, CAD patients reported improvements in both generic and disease-specific HRQoL, however CR participation did not influence this outcome. This may be explained by biases in CR enrollment, whereby acute patients, who may be less limited in HRQoL compared to stable, chronic patients, are targeted for CR participation. Further investigation is required so CR programs maximize the quality of life benefits to all potential CR patients.