Inflammatory biomarkers and long-term outcome in young patients three months after a first myocardial infarction.

BACKGROUND: Studies on predictive value of circulating inflammatory biomarkers after myocardial infarction (MI) have often been limited by blood sampling only in an acute setting and short follow-up time. We aimed to compare the long-term predictive value of nine inflammatory biomarkers, known to be involved in atherosclerosis, in young patients investigated three months after a first-time MI. METHODS: Nine biomarkers (high-sensitivity C-reactive protein, interleukin (IL)-6, IL-18, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, serum amyloid A and tumor necrosis factor-alfa) were sampled in 382 young (<60 years) patients and in age and sex-matched controls, three months after a first-time MI between 1996 and 2000. Swedish national patient registers were used to determine cardiovascular (CV) outcomes during 20 years of follow-up. RESULTS: In cases, random forest models identified IL-6 as the most important predictor of the primary composite endpoint of death, heart failure (HF) or MI hospitalization, and the separate endpoints death and HF hospitalization. IL-18 was the most important predictor of MI hospitalization. In a Cox regression, the highest tertile of IL-6 was associated with the composite endpoint (HR (95% CI) 1.91 (1.31-2.79)), death (2.38 (1.42-3.98)) and HF hospitalization (2.70 (1.32-5.50)), when adjusting for age, sex and CV risk factors. The highest tertile of IL-18 was associated with MI hospitalization (2.31 (1.08-4.91)) when severity of coronary atherosclerosis was added to the same type of model. CONCLUSIONS: When nine inflammatory markers involved in atherosclerosis were analyzed three months after the acute event in young MI patients, IL-6 and IL-18 were the most important biomarkers to predict long-term CV outcomes during 20 years of follow-up.

Iron deficiency in new onset heart failure: association with clinical factors and quality of life.

AIMS: The prevalence of iron deficiency (ID) in newly diagnosed heart failure (HF) and the progression of ID in patients after initiation of HF therapy are unknown. We aimed to describe the natural trajectory of ID in patients with new onset HF during the first year after HF diagnosis, assessing associations between ID, clinical factors, and quality of life (QoL). METHODS AND RESULTS: A prospective cohort of patients with new onset HF in hospitals or outpatient clinics at five major hospitals in Stockholm, Sweden, during 2015-2018 were analysed with clinical assessment, electrocardiogram, blood samples including iron levels, Minnesota living with heart failure questionnaire (MLHFQ), and echocardiogram at baseline and after 12 months. Of 547 patients with new-onset HF, 482 (88%) had complete iron data at baseline. Mean age was 70 years (interquartile range 61-77) and 311 (65%) were men; 55% of patients had ejection fraction (EF) ≤ 40%, 19% had EF 41-49%, and 26% had HF with preserved EF (HFpEF). At baseline, 163 patients (34%) had ID defined as ferritin <100 µg/L or ferritin 100-299 µg/L and transferrin saturation <20%. After 12 months of follow-up, 119 (32%) had ID of the 368 patients who had complete iron data both at baseline and after 12 months and did not receive intravenous (i.v.) iron during follow-up. During the first year after HF diagnosis, 19% had persistent ID, 13% developed ID, 11% resolved ID, and 57% never had ID, consequently 24% changed their classification. Anaemia at baseline was the strongest independent predictor of ID 1 year after diagnosis [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.88-8.13, P < 0.001], followed by HF hospitalization (OR 2.21, 95% CI 1.24-3.95, P < 0.01), female sex (OR 2.04, 95% CI 1.25-3.32, P < 0.01), HFpEF (OR 1.96, 95% CI 1.13-3.39, P < 0.05), and diabetes mellitus (OR 1.92, 95% CI 1.06-3.48, P < 0.05). ID was associated with low QoL at baseline (MLHFQ score mean difference 7.4 points, 95% CI 3.1-11.7, P < 0.001), but not at follow-up. CONCLUSIONS: About one third of patients with new onset HF had ID both at the time of HF diagnosis and after 1 year, though a quarter of the patients changed their ID status. Patients with anaemia, HF hospitalization, female gender, HFpEF, or diabetes mellitus at baseline were more likely to have ID after 1 year implying that these should be carefully screened for ID to find those in need of i.v. iron treatment.

Reduced stress perfusion in myocardial infarction with nonobstructive coronary arteries.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) has several possible underlying causes, including coronary microvascular dysfunction (CMD). Early cardiovascular magnetic resonance imaging (CMR) is recommended, however cannot provide a diagnosis in 25% of cases. Quantitative stress CMR perfusion mapping can identify CMD, however it is unknown if CMD is present during long-term follow-up of MINOCA patients. Therefore, this study aimed to evaluate presence of CMD during long-term follow-up in MINOCA patients with an initial normal CMR scan. MINOCA patients from the second Stockholm myocardial infarction with normal coronaries study (SMINC-2), with a normal CMR scan at median 3 days after hospitalization were investigated with comprehensive CMR including stress perfusion mapping a median of 5 years after the index event, together with age- and sex-matched volunteers without symptomatic ischemic heart disease. Cardiovascular risk factors, medication and symptoms of myocardial ischemia measured by the Seattle Angina Questionnaire 7 (SAQ-7), were registered. In total, 15 patients with MINOCA and an initial normal CMR scan (59 ± 7 years old, 60% female), and 15 age- and sex-matched volunteers, underwent CMR. Patients with MINOCA and an initial normal CMR scan had lower global stress perfusion compared to volunteers (2.83 ± 1.8 vs 3.53 ± 0.7 ml/min/g, p = 0.02). There were no differences in other CMR parameters, hemodynamic parameters, or cardiovascular risk factors, except for more frequent use of statins in the MINOCA patient group compared to volunteers. In conclusion, global stress perfusion is lower in MINOCA patients during follow-up, compared to age- and sex-matched volunteers, suggesting that CMD may be a possible pathophysiological mechanism in MINOCA.Clinical Trial Registration: Clinicaltrials.gov identifier NCT02318498. Registered 2014-12-17.

Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function.

BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction. METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 ml/min/1.73 m2 was tested. RESULTS: Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 ml/min/ 1.73 m2. CONCLUSIONS: Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.

Risk for Acute Myocardial Infarction After Ophthalmologic Procedures.

BACKGROUND: Preoperative cardiovascular evaluations are frequently done before ambulatory ophthalmologic procedures. However, whether these procedures can trigger an acute myocardial infarction (AMI) is unknown. OBJECTIVE: To assess the short-term risk for AMI associated with ophthalmologic procedures. DESIGN: Case-crossover design. SETTING: Population-based nationwide study from Norway and Sweden. PARTICIPANTS: First-time patients with AMI, aged 40 years and older, identified via inpatient registries and linked to outpatient surgical procedures in Norway (2008 to 2014) and Sweden (2001 to 2014), respectively. MEASUREMENTS: Using self-matching, for each participant, exposure to ophthalmologic procedures in the 0 to 7 days before AMI diagnosis (hazard period) was compared with an 8-day period 30 days earlier, that is, days 29 to 36 before AMI (control period) to estimate the relative risk for an AMI the week after an ophthalmologic procedure. The odds ratios (ORs) with 95% CIs were calculated, using conditional logistic regression. Only patients who had a procedure of interest during either the hazard or control period were included. RESULTS: For the 806 patients with AMI included in this study, there was a lower likelihood of AMI in the week after an ophthalmologic procedure than during the control week (OR, 0.83; 95% CI, 0.75 to 0.91). Furthermore, there was no evidence of increased risk for AMI when analyses were stratified by surgery subtype, anesthesia (local or general), duration, invasiveness (low, intermediate, or high), patient's age (<65 years or ≥65 years), or comorbidity (none vs. any). LIMITATION: Potential bias from time-varying confounders between the hazard and the control periods. CONCLUSION: Ophthalmologic procedures done in an outpatient setting did not seem to be associated with an increased risk for AMI. PRIMARY FUNDING SOURCE: Central Norway Regional Health Authority and the Swedish Research Council.

Plasma catecholamine levels in the acute and subacute stages of takotsubo syndrome: Results from the Stockholm myocardial infarction with normal coronaries 2 study.

AIMS: It is well-accepted that takotsubo syndrome (TS) is characterized by a massive surge of plasma catecholamines despite lack of solid evidence. The objective of this study was to examine the hypothesis of a massive catecholamine elevation in TS by studying plasma-free catecholamine metabolites in patients participating in the Stockholm myocardial infarction (MI) with normal coronaries 2 (SMINC-2) study where TS constituted more than one third of the patients. METHODS AND RESULTS: The patients included in the SMINC-2 study were classified, according to cardiac magnetic resonance (CMR) imaging findings (148 patients), which was performed at a median of 3 days after hospital admission. Plasma-free catecholamine metabolites; metanephrine, normetanephrine, and methoxy-tyramine were measured on day 2-4 after admission. Catecholamine metabolite levels were available in 125 patients. One hundred and ten (88%) of the 125 patients included in SMINC-2 study, and 38 (86.4%) of the 44 patients with TS had completely normal plasma metanephrine and normetanephrine levels. All patients had normal plasma methoxy-tyramine levels. Fourteen (11.2%) of the 125 patients included in SMINC-2 study, and 5 (11.6%) of the 43 patients with TS had mild elevations (approximately 1.2 times the upper normal limits) of either plasma metanephrine or normetanephrine. One patient with pheochromocytoma-triggered TS had marked elevation of plasma metanephrine and mild elevation of plasma normetanephrine. There were no significant differences between the number or degree of catecholamine metabolite elevations between the different groups of patients with CMR imaging diagnosis included in SMINC-2 study. CONCLUSION: There was no evidence of massive catecholamine elevations in the acute and subacute stages of TS apart from one patient with pheochromocytoma-induced TS. Most of the TS patients had normal catecholamine metabolites indicating that blood-borne catecholamines do not play a direct role in the pathogenesis of TS.

Short- and Long-Term Clinical Outcomes for Patients With Takotsubo Syndrome and Patients With Myocardial Infarction: A Report From the Swedish Coronary Angiography and Angioplasty Registry.

Background Takotsubo syndrome (TS) is a potentially life-threatening acute cardiac syndrome with a clinical presentation similar to myocardial infarction and for which the natural history, management, and outcome remain incompletely understood. Our aim was to assess the relative short-term mortality risk of TS, ST-segment-elevation myocardial infarction (STEMI), and non-STEMI (NSTEMI) and to identify predictors of in-hospital complications and poor prognosis in patients with TS. Methods and Results This is an observational cohort study based on the data from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). We included all patients (n=117 720) who underwent coronary angiography in Sweden attributed to TS (N=2898 [2.5%]), STEMI (N=48 493 [41.2%]), or NSTEMI (N=66 329 [56.3%]) between January 2009 and February 2018. We compared patients with TS to those with NSTEMI or STEMI. The primary end point was all-cause mortality at 30 days. Secondary outcomes were acute heart failure (Killip Class ≥2) and cardiogenic shock (Killip Class 4) at the time of angiography. Patients with TS were more often women compared with patients with STEMI or NSTEMI. TS was associated with unadjusted and adjusted 30-day mortality risks lower than STEMI (adjusted hazard ratio [adjHR], 0.60; 95% CI, 0.48-0.76; P<0.001), but higher than NSTEMI (adjHR, 2.70; 95% CI, 2.14-3.41; P<0.001). Compared with STEMI, TS was associated with a similar risk of acute heart failure (adjHR, 1.26; 95% CI, 0.91-1.76; P=0.16) but a lower risk of cardiogenic shock (adjHR, 0.55; 95% CI, 0.34-0.89; P=0.02). The relative 30-day mortality risk for TS versus STEMI and NSTEMI was higher for smokers than nonsmokers (adjusted P interaction STEMI=0.01 and P interaction NSTEMI=0.01). Conclusions The 30-day mortality rate in TS was higher than in NSTEMI but lower than STEMI despite a similar risk of acute heart failure in TS and STEMI. Among patients with TS, smoking was an independent predictor of mortality.

Increased iron absorption in patients with chronic heart failure and iron deficiency.

BACKGROUND: Iron deficiency (ID) is common in patients with chronic heart failure (CHF), but the underlying causes are not fully understood. We investigated whether ID is associated with decreased iron absorption in patients with CHF. METHODS AND RESULTS: We performed an oral iron-absorption test in 30 patients and 12 controls. The patients had CHF with reduced (n = 15) or preserved (n = 15) ejection fraction and ID, defined as s-ferritin < 100 µg/L, or s-ferritin 100-299 µg/L and transferrin saturation < 20%. The controls had no HF or ID and were of similar age and gender. Blood samples were taken before and 2 hours after ingestion of 100 mg ferroglycin sulphate. The primary endpoint was the delta plasma iron at 2 hours. The delta plasma iron was higher in the group with HF than in the control group (median increase 83.8 [61.5;128.5] µg/dL in HF vs 47.5 [30.7;61.5] µg/dL in controls, P = 0.001), indicating increased iron absorption. There was no significant difference between the groups with preserved or reduced ejection fraction (P = 0.46). CONCLUSION: We found increased iron absorption in patients with CHF and ID compared to controls without ID and HF, indicating that reduced iron absorption is not a primary cause of the high prevalence of ID in patients with CHF. CLINICAL TRIAL REGISTRATION: EudraCT 2017-000158-21.

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.

Trigger factors in takotsubo syndrome - A systematic review of case reports.

INTRODUCTION: Takotsubo syndrome is an acute heart failure syndrome often preceded by a trigger factor of physical or emotional origin, although the proportion is unclear. The aim of the present study was to determine how common different trigger factors are in takotsubo syndrome divided by sex and age in women. MATERIAL AND METHODS: The study consisted of a systematic review of all available case reports in PubMed and Web of Science up to March 2018. Trigger factors were categorized into physical and emotional trigger factors. RESULTS: Males had to a higher degree experienced a trigger factor (92.6%) compared to females (81.9%, p < .001). Physical trigger factors were most common (67.3%). Males had to a higher degree experienced a physical trigger factor (85.7%) compared to females (63.5%, p < .001). Females ≤50 years of age had to a higher degree experienced a trigger factor (90.8%) compared to females >50 years of age (79.2%, p < .001). Additionally, females ≤50 years of age had to a higher degree experienced a physical trigger factor (75.6%) compared to females >50 years of age (59.3%, p < .01). CONCLUSION: A physical trigger factor is more common than an emotional trigger factor in takotsubo syndrome. Physical triggers includes drugs, surgery and central nervous system conditions. Furthermore, females ≤50 years of age and males more often have an evident trigger factor and it is more often physical, compared to the most common patient, a female >50 years of age.

Epidemiology, pathogenesis, and management of takotsubo syndrome.

Takotsubo syndrome is a recently recognized acute cardiac disease entity with a clinical presentation resembling that of an acute coronary syndrome. The typical takotsubo syndrome patient has a unique circumferential left (bi-) ventricular contraction abnormality profile that extends beyond a coronary artery supply territory and appears to follow the anatomical cardiac sympathetic innervation. The syndrome predominantly affects postmenopausal women and is often preceded by emotional or physical stress. Patients with predisposing factors such as malignancy and other chronic comorbidities are more prone to suffer from takotsubo syndrome. The pathogenesis of takotsubo syndrome is elusive. Several pathophysiological mechanisms involving myocardial ischemia (multivessel coronary artery spasm, microvascular dysfunction, aborted myocardial infarction), left ventricular outlet tract obstruction, blood-borne catecholamine myocardial toxicity, epinephrine-induced switch in signal trafficking, and autonomic nervous system dysfunction have been proposed. The syndrome is usually reversible; nevertheless, during the acute stage, a substantial number of patients develop severe complications such as arrhythmias, heart failure including pulmonary edema and cardiogenic shock, thromboembolism, cardiac arrest, and rupture. Treatment of precipitating factors, predisposing diseases, and complications is fundamental during the acute stage of the disease. The epidemiology, pathogenesis, and management of takotsubo syndrome are reviewed in this paper.

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.

Myocardial Infarction with Nonobstructive Coronary Arteries: The Importance of Achieving Secondary Prevention Targets.

BACKGROUND: Approximately 5% to 10% of all patients with myocardial infarction have nonobstructive coronary arteries. Studies investigating the importance of follow-up and achievement of conventional secondary prevention targets in these patients are lacking. METHODS: In this analysis from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we investigated 5830 patients with myocardial infarction with nonobstructive coronary arteries (group 1) and 54,637 patients with myocardial infarction with significant coronary artery disease (≥50% stenosis; group 2). Multivariable- and propensity score-adjusted statistics were used to assess the reduction in the 1-year risk of major adverse events associated with prespecified secondary preventive measures: participation in follow-up at 6 to 10 weeks after the hospitalization and achievement of secondary prevention targets (blood pressure and low-density lipoprotein cholesterol levels in the target ranges, nonsmoking, and participation in exercise training). RESULTS: Patients in group 1 were less often followed up compared with patients in group 2 and less often achieved any of the secondary prevention targets. Participation in the 6- to 10-week follow-up was associated with a 3% to 20% risk reduction in group 1, similar as for group 2 according to interaction analysis. The improvement in outcome in group 1 was mainly mediated by achieving target range low-density lipoprotein cholesterol levels (24%-32% risk reduction) and, to a smaller extent, by participation in exercise training (10%-23% risk reduction). CONCLUSIONS: Selected secondary preventive measures are associated with prognostic benefit in patients with myocardial infarction with nonobstructive coronary arteries, in particular achieving target range low-density lipoprotein cholesterol levels. Our results indicate that these patients should receive similar follow-up as myocardial infarction patients with significant coronary stenoses.

Ticagrelor pharmacokinetics and pharmacodynamics in patients with NSTEMI after a 180-mg loading dose.

The pharmacokinetics after a 180-mg loading dose (LD) of ticagrelor has not been thoroughly investigated in NSTEMI patients. We aimed to compare the ticagrelor uptake and on-treatment platelet reactivity between non-ST-segment elevation myocardial infarction (NSTEMI) patients and a control group of patients with stable coronary artery disease (SCAD) undergoing elective percutaneous coronary intervention. We performed an observational, prospective, single-center study including 40 NSTEMI patients and 20 SCAD controls. Key exclusion criteria included ongoing opioid treatment. Both groups received a 180-mg ticagrelor LD, and blood samples were taken pre-dose and 1, 2, 3, 4, 5, and 6 hours post-LD. Plasma concentrations of ticagrelor and its active metabolite AR-C124910XX were determined by validated methods. Platelet aggregation was tested using ADP-induced multiple electrode aggregometry. The primary endpoint was the time to maximal ticagrelor concentration (Tmax). Clinical trial registration identifier number: NCT02292277. None of the pharmacokinetic variables differed significantly between the groups, including the Tmax of ticagrelor (2.0h [1.0-3.0] versus 2.0h [2.0-3.0], p = 0.393) and the active metabolite AR-C124910XX (3.0 [2.0-4.0] versus 3.0 [2.5-4.0], p = 0.289). High on-treatment platelet reactivity (HPR) was defined as > 46 aggregation units and was at one hour seen in 15% of the NSTEMI patients versus 10% of the controls (p = 1.0). At two hours post the 180-mg ticagrelor LD, 3% of the NSTEMI patients had HPR compared with none of the controls (p = 1.0). In conclusion, the uptake of ticagrelor was not significantly slower in NSTEMI patients not receiving opioids compared with the SCAD controls, leading to adequate onset of platelet inhibition in both groups.

Reproductive and Lifestyle Factors Associated with Endometriosis in a Large Cross-Sectional Population Sample.

OBJECTIVES: Despite the high prevalence of endometriosis among women of reproductive age, risk factors or markers for developing the condition remain largely unknown. Many of the published studies are based on small selected samples. We therefore investigated the relationships of reproductive and lifestyle factors with endometriosis in a large sample of Swedish female twins. MATERIAL AND METHODS: This cross-sectional study included 28,822 women. Among these, endometriosis was reported by 1,228 women and the self-reported diagnosis was confirmed by medical records. Potential risk factors or markers for risk considered were age at menarche, level of education, body mass index (BMI), parity, oral contraceptive (OC) use, infertility, coffee consumption, smoking, and alcohol intake, which were investigated using logistic regression with crude and adjusted analyses. We performed within-pair analysis to examine the sensitivity of the results. RESULTS: Late age at menarche and higher parity showed an inverse association and infertility showed a strong association with endometriosis. We observed positive associations with coffee consumption and smoking and an inverse association with OC use in crude analysis but not in adjusted analysis. There were no significant associations between level of education, BMI, or alcohol intake and endometriosis. Within-pair analysis showed persistent inverse association of parity and association of infertility with endometriosis. CONCLUSIONS: Our study suggests that late age at menarche and higher parity are inversely associated and infertility is strongly associated with endometriosis. Future studies are needed to explore the significance of these factors in the diagnosis of endometriosis and understanding of its etiology.

[Spontaneous coronary artery dissection can cause acute coronary syndrome. Unusual condition that requires thoughtful management and more research]. / Spontan kranskärls-dissektion kan orsaka akut koronart syndrom - Ovanligt tillstånd som kräver genomtänkt handläggning och mer forskning.

Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic injury occurring in the vessel wall caused by either a primary intimal dissection or a primary hematoma in the medial layer. SCAD is more common among women than men and accounts for a small minority of acute coronary syndromes. The causes of SCAD are multifactorial. Peripartum SCAD is most common. Fibromuscular dysplasia has a strong association with SCAD. As spontaneous healing is common in SCAD and PCI is associated with complications an initial conservative approach should always be considered. Medical treatment is based on the underlying cause. Beta blockers are recommended to all patients. The prognosis varies; the highest mortality is reported among women suffering peripartum SCAD. Quality of life is often affected in SCAD patients and accompanied by a high rate of rehospitalizations. More research which focuses on the underlying causes, optimal treatment and rehabilitation is needed.

Acute Systemic Inflammation is Unlikely to Affect Adiponectin and Leptin Synthesis in Humans.

Adipose tissue (AT), classically thought to be merely an energy store, has been shown to produce inflammatory and metabolically active cytokines. Recently, adiponectin and leptin, adipokines primarily synthesized by adipocytes, have attracted considerable attention because inflammation has been suggested to modulate adipokine levels. However, the regulation of adiponectin and leptin is complex and the knowledge about their synthesis within the early onset of inflammation is poorly understood. The aim of this study was to investigate if the synthesis of adiponectin and leptin is affected during the early phase of an acute systemic inflammation. Eighteen healthy subjects were allocated to vaccination against Salmonella typhi or to a control group, and adiponectin and leptin concentrations measured in plasma during 24 h. Nine patients, without markers of inflammation, undergoing open heart surgery were investigated before and after the operation by analysis of plasma levels and AT gene expression of adiponectin and leptin. Plasma interleukin (IL)-6 concentrations were measured in both cohorts. Plasma levels of IL-6 were doubled after vaccination and increased 30-fold after open heart surgery. Plasma levels of adiponectin and leptin were unchanged after vaccination whereas adiponectin and leptin tended to decrease after surgery. The gene expression of adiponectin and leptin was unaltered in omental and subcutaneous AT after surgery. Despite the use of two models of stimulated in vivo systemic inflammation, we found no evidence of an early regulation of adiponectin and leptin synthesis, indicating that these two adipokines are not key elements in an acute systemic inflammation in humans.

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.

Correlation between point-of-care platelet function testing and bleeding after coronary angiography according to two different definitions for bleeding.

Platelet function testing could be useful when assessing the risk for bleeding during treatment with antiplatelet drugs. This has been indicated in several studies, including the Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Bleeding (ARMYDA-BLEEDS) study, which demonstrated that testing with a point-of-care assay correlated with bleeding events after percutaneous coronary intervention. To standardize bleeding definitions, the Bleeding Academic Research Consortium (BARC) published a consensus report, which is in need of data-driven validation. Hence, the investigators conducted an observational, prospective, single-center study of 474 patients receiving clopidogrel and aspirin who underwent coronary angiography with or without percutaneous coronary intervention from October 2006 to May 2011. Platelet reactivity was measured with adenosine diphosphate-induced single-platelet function testing (Plateletworks) at the start of coronary angiography. The primary end point was the 30-day incidence of bleeding as defined by BARC and ARMYDA-BLEEDS. The aim of the present study was to investigate the relation between on-treatment platelet reactivity and the 30-day incidence of bleeding complications according to the BARC and ARMYDA-BLEEDS definitions. Patients in the first platelet aggregation quartile had a higher frequency of type 2 or higher BARC bleeding and ARMYDA-BLEEDS-defined bleeding <30 days after coronary angiography compared with the fourth quartile (16.9% vs 6.7%, p = 0.014, and 8.5% vs 1.7%, p = 0.016, respectively) and the third quartile (16.9% vs 7.7%, p = 0.031, and 8.5% vs 2.6%, p = 0.048, respectively). In conclusion, patients with low on-treatment platelet reactivity at the time of intervention had a significantly higher incidence of bleeding according to the BARC and ARMYDA-BLEEDS definitions <30 days after coronary angiography with or without percutaneous coronary intervention.