Health-related quality-of-life up to one year after myocardial infarction with non-obstructive coronary arteries.

AIMS: Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) are a heterogenous group and previous studies indicate a decreased Health-related quality-of-life (HRQoL) compared with patients with myocardial infarction with obstructive coronary artery disease and healthy individuals. However, longitudinal data are scarce. Therefore, the aim was to explore HRQoL among patients with MINOCA during a one-year period after the acute event in comparison with a group of healthy individuals and to describe HRQoL in patients with Takotsubo Syndrome (TTS). METHODS AND RESULTS: Patients with MINOCA were recruited from five hospitals in the Stockholm region (SMINC-2 study, clinical trials: NCT2318498). Patients responded to the HRQoL questionnaire RAND-36 between days 2-4, after 6 and 12 months respectively. A sample of population-based individuals was used as a comparison group. A total of 142 MINOCA patients, (70% women) mean age of 56 years, responded. A population-based sample of 317 volunteers (66% women) mean age of 57 years. Patients with MINOCA scored lower than the comparison group in the domains role functioning physical, social functioning, and role functioning emotional (P = 0.01-0.02) at 12 months. In these domains of HRQoL there was no improvement in MINOCA patients during 12 months follow-up. In the domains of energy/fatigue vitality and emotional well-being the scores improved and were similar to the comparison group at 12 months. Patients with TTS scored generally lower on RAND-36 than MINOCA patients without TTS. CONCLUSION: Physical, social, and emotional functioning did not improve during the first year after MINOCA, indicating a need for increased follow-up including psychological support.

Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries.

BACKGROUND: Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). OBJECTIVES: To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C-protein C inhibitor (APC-PCI) complex. METHODS: Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case-control study. Autoantibodies (IgA/G/M) targeting cardiolipin and ß2 glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC-PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. RESULTS: Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-ß2 glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC-PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. CONCLUSIONS: aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability-measured by increased levels of the APC-PCI complex-were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.

Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries.

BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD). METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age- and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses. RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-κ-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls. CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts.

Plasma biomarker levels and non-obstructive coronary artery disease determined by coronary computed tomography angiography.

PURPOSE: Coronary computed tomography angiography (CTA) and several circulating biomarkers have prognostic value regarding cardiovascular disease (CVD) events, but their association is incompletely studied. We aimed to investigate whether markers of lipid metabolism, inflammation and kidney function could predict non-obstructive coronary artery disease (CAD) determined by coronary CTA, in a low-to-intermediate-risk group. METHODS: Coronary CTA and laboratory testing were performed for 115 subjects (45-70 years), with low prevalence of CVD risk factors, predominantly low-to-intermediate Framingham risk and normal or mildly reduced kidney function. RESULTS: Forty-nine (43%) had no CAD at coronary CTA, and 66 (57%) had CAD in ≥1 segment (stenosis < 50%). Adiponectin was inversely associated with CAD, and lipoprotein(a) and cystatin C were associated with CAD at coronary CTA. In multivariable logistic regression, cystatin C remained an independent predictor of CAD (OR: 2·50, 95% CI: 1·12-5·59). Cystatin C also correlated to the number of diseased segments (rs  = 0·25, P<0·01). CONCLUSION: Higher plasma levels of cystatin C were associated with non-obstructive CAD at coronary CTA in subjects with low-to-intermediate CVD risk and normal to mildly reduced kidney function.

Prevalence of Myocardial Bridging in Patients With Myocardial Infarction and Nonobstructed Coronary Arteries.

Mechanisms of acute myocardial infarction and nonobstructed coronary arteries (MINOCA) are incompletely understood. Myocardial bridging (MB) is usually considered a benign congenital variant, but serious complications have been reported. MB has also been proposed as a cause of takotsubo syndrome (TS). We aimed to examine whether MB was more frequent in patients with MINOCA or TS than in age- and gender-matched controls and to compare the MB detection rates of coronary computed tomography angiography (CTA) and invasive coronary angiography (ICA). Patients with MINOCA (n = 57) and age- and gender-matched controls (n = 58), aged 45 to 70 were enrolled. Myocarditis was excluded by cardiovascular magnetic resonance imaging. Patients with TS (n = 15) were considered as a subgroup and therefore not excluded. Patients with MINOCA underwent ICA and all study participants underwent coronary CTA. All examinations were reviewed with focus on MB. Among 57 MINOCA patients, 15 MINOCA patients with TS and 58 controls, MB was demonstrated in 28 patients (49%), 8 patients (53%), and 26 patients (45%), respectively. There were no statistically significant differences regarding the prevalence of MB or the type, location, length, or thickness of MB. There was a statistically significant difference (p <0.01) between the detection rates of coronary CTA and ICA that demonstrated MB in 54 subjects (47%) and 13 subjects (23%), respectively. In conclusion, MB was frequent with a similar prevalence in patients with MINOCA, patients with TS and controls. This suggests that there is no causal link between MB and MINOCA or TS. Furthermore, coronary CTA detects MB at a significantly higher rate than ICA.

Risk Factors and Markers for Acute Myocardial Infarction With Angiographically Normal Coronary Arteries.

Myocardial Infarction with normal coronary arteries (MINCA) is common with a prevalence of 1% to 12% of all myocardial infarctions. The pathogenic mechanisms of MINCA are still unknown, but endothelial dysfunction has been suggested as a possible cause. To investigate risk factors and markers for MINCA, we conducted a case-control study. Considering the reported low prevalence of classical risk factors for coronary heart disease (CHD) in some but not all studies, our hypothesis was that endothelial function and intima-media thickness (IMT) were better, respectively lower, than CHD controls. One hundred patients with MINCA fulfilling diagnostic criteria according to the European Society of Cardiology/American Collage of Cardiology/American Heart Association universal definition of myocardial infarction with myocarditis excluded by cardiac magnetic resonance imaging were investigated. Risk factors, endothelial function (EndoPAT), and IMT were compared to gender- and age-matched patients with myocardial infarction and CHD, respectively healthy controls. Smoking, hypertension, impaired glucose tolerance and diabetes mellitus, inflammatory disease, and psychiatric disorders were more common in patients with MINCA than in healthy controls. In contrast to patients with CHD, the lipid profile was antiatherogenic with low low-density lipoprotein and high high-density lipoprotein cholesterol. There were no major differences between the groups regarding endothelial function and IMT that were in the normal range. In conclusion, the present study showed that MINCA was associated with many established cardiovascular risk factors without major differences in atherosclerosis markers. MINCA patients recalled a high prevalence of emotional stress before admission that together with previous psychiatric vulnerability and female gender speaks strongly in favor of Takotsubo syndrome being an important cause of MINCA.

Neither endothelial function nor carotid artery intima-media thickness predicts coronary computed tomography angiography plaque burden in clinically healthy subjects: a cross-sectional study.

BACKGROUND: Cardiovascular risk assessment is usually based on traditional risk factors and risk assessment algorithms. However, a number of risk markers that might provide additional predictive power have been identified. Endothelial function determined by digital reactive hyperemia peripheral arterial tonometry (RH-PAT) and carotid artery intima-media thickness (IMT) have both been proposed as surrogate markers for coronary artery disease (CAD). We aimed to examine the ability of RH-PAT and IMT to predict coronary computed tomography angiography (CTA) plaque burden in clinically healthy subjects. METHODS: Fifty-eight clinically healthy volunteers (50-73 years old) underwent testing for RH-PAT and IMT as well as coronary CTA, including coronary artery calcium (CAC) scoring. Coronary CTA was analyzed with respect to any atheromatous plaques, stenotic as well as non-stenotic. The Mann-Whitney U-test was used to compare the groups with and without CAD and the Spearman test was used to test for correlation between variables. RESULTS: Twenty-five (43 %) subjects had normal coronary arteries, without any signs of atherosclerosis. The median (range) number of diseased segments was 1 (0-10), RH-PAT index 2.2 (1.4-4.9), IMT 0.70 (0.49-0.99) mm and CAC 4 (0-1882). There was no association between presence or extent of CAD and RH-PAT index (Spearman correlation coefficient rs = 0.13) or IMT (rs = 0.098). As expected, CAC was strongly correlated to presence and extent of CAD by coronary CTA (rs =0.86; p < 0.0001). CONCLUSIONS: Neither evaluation of endothelial function by RH-PAT nor assessment of carotid artery IMT can reliably be used to predict coronary CTA plaque burden in clinically healthy subjects.

Coronary plaque burden, as determined by cardiac computed tomography, in patients with myocardial infarction and angiographically normal coronary arteries compared to healthy volunteers: a prospective multicenter observational study.

OBJECTIVES: Patients presenting with acute myocardial infarction and angiographically normal coronary arteries (MINCA) represent a diagnostic and a therapeutic challenge. Cardiac computed tomography (CT) allows detection of coronary artery disease (CAD) even in the absence of significant stenosis. We aimed to investigate whether patients suffering from MINCA had a greater coronary plaque burden, as determined by cardiac CT, than a matched group of healthy volunteers. METHODS: Consecutive patients, aged 45 to 70, with MINCA were enrolled in the Stockholm metropolitan area. Patients with myocarditis were excluded using cardiovascular magnetic resonance imaging. Remaining patients underwent cardiac CT, as did a reference group of healthy volunteers matched by age and gender, with no known cardiovascular disease. Plaque burden was evaluated semi-quantitatively on a per patient and a per segment level. RESULTS: Despite a higher prevalence of smoking and hypertension, patients with MINCA did not have more CAD than healthy volunteers. Among 57 MINCA patients and 58 volunteers no signs of CAD were found in 24 (42%) and 25 (43%) respectively. On a per segment level, MINCA patients had less segments with stenosis ≥ 20% (2% vs. 5%, p<0.01), as well as a smaller proportion of large (2% vs. 4%, p<0.05) and mixed type plaques (1% vs. 4%, p<0.01). The median coronary calcium score did not differ between MINCA patients and healthy volunteers (6 vs. 8, ns). CONCLUSIONS: MINCA patients with no or minimal angiographic stenosis do not have more coronary atherosclerosis than healthy volunteers, and a large proportion of these patients do not have any signs of CAD, as determined by cardiac CT. The MINCA patient group is probably heterogeneous, with a variety of different underlying mechanisms. Non-obstructive CAD is most likely not the most prevalent cause of myocardial infarction in this patient group.