Gender but not diabetes, hypertension or smoking affects infarct evolution in ST-elevation myocardial infarction patients - data from the CHILL-MI, MITOCARE and SOCCER trials.

BACKGROUND: Infarct evolution rate and response to acute reperfusion therapy may differ between patients, which is important to consider for accurate management and treatment of patients with ST-elevation myocardial infarction (STEMI). The aim of this study was therefore to investigate the association of infarct size and myocardial salvage with gender, smoking status, presence of diabetes or history of hypertension in a cohort of STEMI-patients. METHODS: Patients (n = 301) with first-time STEMI from the three recent multi-center trials (CHILL-MI, MITOCARE and SOCCER) underwent cardiac magnetic resonance (CMR) imaging to determine myocardium at risk (MaR) and infarct size (IS). Myocardial salvage index (MSI) was calculated as MSI = 1-IS/MaR. Pain to balloon time, culprit vessel, trial treatments, age, TIMI grade flow and collateral flow by Rentrop grading were included as explanatory variables in the statistical model. RESULTS: Women (n = 66) had significantly smaller MaR (mean difference: 5.0 ± 1.5% of left ventricle (LV), p < 0.01), smaller IS (mean difference: 5.1 ± 1.4% of LV, p = 0.03), and larger MSI (mean difference: 9.6 ± 2.8% of LV, p < 0.01) compared to men (n = 238). These differences remained significant when adjusting for other explanatory variables. There were no significant effects on MaR, IS or MSI for diabetes, hypertension or smoking. CONCLUSIONS: Female gender is associated with higher myocardial salvage and smaller infarct size suggesting a pathophysiological difference in infarct evolution between men and women.

Transthoracic Doppler echocardiography compared with positron emission tomography for assessment of coronary microvascular dysfunction: The iPOWER study.

BACKGROUND: Coronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard for measuring coronary microvascular function but has limited availability. We compared TTDE CFVR with PET MBFR in women with angina pectoris and no obstructive coronary artery disease and assessed repeatability of TTDE CFVR. METHODS: From a cohort of women with angina and no obstructive coronary artery stenosis at invasive coronary angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET with adenosine was successfully measured in 107 subjects. Repeatability of TTDE CFVR was assessed in 10 symptomatic women and in 10 healthy individuals. RESULTS: MBFR was systematically higher than CFVR. Median MBFR (interquartile range, IQR) was 2.68 (2.29-3.10) and CFVR (IQR) was 2.31 (1.89-2.72). Pearson's correlation coefficient was 0.36 (p<0.01). Limits of agreement (2·standard deviation) assessed by the Bland-Altman (confidence interval, CI) method was 1.49 (1.29;1.69) and unaffected by time-interval between examinations. Results were similar when adjusting for rate pressure product or focusing on perfusion of the left anterior descending artery region. Limits of agreement (CI) for repeated CFVR in 10 healthy individuals and in 10 women with angina was 0.44 (0.21;0.68) and 0.48 (0.22; 0.74), respectively. CONCLUSION: CFVR had a good repeatability, but the agreement between CFVR and MBFR was modest. Divergence could be due to methodology differences; TTDE estimates flow velocities whereas PET estimates myocardial blood flow.

Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease: The iPOWER Study.

BACKGROUND: The majority of women with angina-like chest pain have no obstructive coronary artery disease when evaluated with coronary angiography. Coronary microvascular dysfunction is a possible explanation and associated with a poor prognosis. This study evaluated the prevalence of coronary microvascular dysfunction and the association with symptoms, cardiovascular risk factors, psychosocial factors, and results from diagnostic stress testing. METHODS AND RESULTS: After screening 3568 women, 963 women with angina-like chest pain and a diagnostic coronary angiogram without significant coronary artery stenosis (<50%) were consecutively included. Mean age (SD) was 62.1 (9.7). Assessment included demographic and clinical data, blood samples, questionnaires, and transthoracic echocardiography during rest and high-dose dipyridamole (0.84 mg/kg) with measurement of coronary flow velocity reserve (CFVR) by Doppler examination of the left anterior descending coronary artery. CFVR was successfully measured in 919 (95%) women. Median (IQR) CFVR was 2.33 (1.98-2.76), and 241 (26%) had markedly impaired CFVR (<2). In multivariable regression analysis, predictors of impaired CFVR were age (P<0.01), hypertension (P=0.02), current smoking (P<0.01), elevated heart rate (P<0.01), and low high-density lipoprotein cholesterol (P=0.02), but these variables explained only a little of the CFVR variation (r(2)=0.09). CFVR was not associated with chest pain characteristics or results from diagnostic stress testing. CONCLUSION: Impaired CFVR was detected in a substantial proportion, which suggests that coronary microvascular dysfunction plays a role in the development of angina pectoris. CFVR was associated with few cardiovascular risk factors, suggesting that CFVR is an independent parameter in the risk evaluation of these women. Symptom characteristics and results from stress testing did not identify individuals with impaired CFVR.

Physical fitness and amount of asthma and asthma-like symptoms from childhood to adulthood.

OBJECTIVE: The potential benefits of physical activity on the development of respiratory symptoms are not well known. The present study investigated the longitudinal association between physical fitness and the development of asthma-like symptoms from childhood to adulthood in a longitudinal community-based study. METHODS: Participants were assessed at ages 9, 15, 20 and 29 years. Asthma-like symptoms and physical fitness was assessed at each age. RESULTS: Tracking for physical fitness was high from age 9 to 29 years. Using logistic regression, high physical fitness at age 9 predicted a lower prevalence of asthma-like symptoms at ages 9, 20 and 29 years. Asthma at age 9 and female sex and smoking at any age were also independently associated with the presence of asthma-like symptoms. Our findings suggest that the risk for the development of asthma is reduced by 3% and of asthma-like symptoms reduced by 2% from early adolescence to young adulthood (ages 9-29 years) by increasing the maximal workload with 1 W/kg. CONCLUSION: This finding provide further evidence of a possible beneficial effect of physical activity in childhood on the development of respiratory symptoms in adulthood and supports the notion that the lower levels of physical activity in recent decades may have contributed to an increase in the prevalence of asthma and asthma-like symptoms.

Prevention of contrast-induced nephropathy with N-acetylcysteine or sodium bicarbonate in patients with ST-segment-myocardial infarction: a prospective, randomized, open-labeled trial.

BACKGROUND: Contrast-induced nephropathy (CIN) is a serious condition in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. We compared the risk of acute CIN and the influence of preventive strategies in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: A total of 720 patients were randomized in the Prevention of Contrast-induced Nephropathy in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (CINSTEMI) trial. Patients were randomly assigned in a 1:1:1:1 ratio to receive hydration with sodium chloride together with 1 of 4 prophylactic regimes (1) N-acetylcysteine (NAC), (2) sodium bicarbonate (NaHCO3) infusion, (3) NAC in combination with NaHCO3, or (4) hydration with sodium chloride infusion alone. Patients in cardiogenic shock were excluded. Acute CIN was defined as an increase in serum creatinine concentration >25% from the baseline value within a 3-day period. Overall, CIN occurred in 141 (21.9%) patients. The prevention treatment with NAC, NaHCO3, or the combined NAC and NaHCO3 did not reduce the rate of CIN significantly compared with hydration with intravenous sodium chloride infusion alone (20.1% versus 20.1% versus 20.8% versus 26.5%; P=NS). However, an increase in serum creatinine >25% from the baseline value to 30 day was significantly lower in patients treated with combined NAC and NaHCO3 (18.7% versus 19.1% versus 9.2% versus 21.3%; P=0.033). CONCLUSIONS: Treatment with NAC or NaHCO3 did not reduce the rate of acute CIN significantly. Combined treatment with NAC and NaHCO3 may reduce the risk of renal dysfunction after 30 days. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01160627.

Graft patency after off-pump coronary artery bypass surgery is inferior even with identical heparinization protocols: results from the Danish On-pump Versus Off-pump Randomization Study (DOORS).

OBJECTIVE: To determine whether graft patency after on-pump and off-pump coronary artery bypass surgery is similar when performed using the same heparinization protocol. METHODS: In a randomized, controlled, multicenter trial, 900 patients more than 70 years of age received either on-pump or off-pump coronary artery bypass surgery. Heparin was given to achieve an activated clotting time of 400 seconds before arteriotomy in both groups. After the procedure, protamine sulfate was given to revert the activated clotting time to less than 120 seconds. Coronary angiography was performed 6 months after the operation and graft patency was assessed by independent blinded observers. RESULTS: A total of 481 patients underwent angiography. In the off-pump group, 561 (79%) of 710 grafts were open, 65 (9%) were stenotic, and 84 (12%) were occluded. In the on-pump group, 549 (86%) of 650 grafts were open, 38 (5%) were stenotic, and 63 (9%) were occluded. The difference between the proportion of open grafts was statistically significant in favor of on-pump surgery (P=.01). The proportion of open left internal thoracic artery grafts was 95% in both groups. Perioperative use of intracoronary shunts did not increase the risk of stenosis of the coronary artery distal to the anastomosis. CONCLUSIONS: Despite comparable heparinization, graft patency after off-pump surgery was inferior to that after on-pump surgery.

Associations between airway hyperresponsiveness, obesity and lipoproteins in a longitudinal cohort.

BACKGROUND: Epidemiological data have linked obesity with an increased risk of asthma, but the mechanisms responsible for this relationship remain unknown. One possible mechanism, which has received little attention, could be the effect of cholesterol metabolism on airway smooth muscle function. The present study investigated the association between airway hyperresponsiveness (AHR) to methacholine and body mass index (BMI) and plasma lipoproteins [low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol]. METHODS: Associations between AHR, BMI and plasma lipoproteins were assessed in a population-based cohort at ages 14 and 20 years. RESULTS: In unadjusted analyses, higher LDL cholesterol levels at age 14 were associated with AHR at age 20 in both sexes (P < 0.05). HDL, LDL/HDL ratio and total cholesterol were not associated with AHR. In multiple regression analyses adjusted for sex, lung function, smoking and asthma, only higher levels of BMI at age 14 or 20 years were significantly associated with increased AHR at age 20 years, while neither LDL, HDL and LDL/HDL ratio nor total cholesterol were significantly associated with AHR. CONCLUSION: We confirmed that in teenagers there is a strong association between BMI and AHR to methacholine. This association seems to be independent of the plasma lipoprotein levels at that age.

[Myocardial infarction in 22 year-old male with essential thrombocythaemia]. / Myokardieinfarkt hos 22-årig mand med essentiel trombocytose.

Essential thrombocythaemia (ET) is an acquired myeloproliferative disorder that causes thrombosis and haemorrhage. The association of myocardial infarction with ET is rare. We here describe a 22 year-old male patient with ET who presented with acute myocardial infarction. Coronary angiography showed multi-vessel thrombosis. Percutaneous coronary angioplasty was successfully performed. The patient was treated with abciximab after percutaneous coronary intervention. Bone marrow biopsy confirmed ET; treatment was started with interferon-alpha along with aspirin and clopidogrel without haemorrhagic complications.

No relationship between lung function and high-sensitive C-reactive protein in adolescence.

INTRODUCTION: Several studies on adults have indicated that lower spirometric lung function may be associated with increased systemic inflammation, but no studies have investigated if this association is already present in adolescence. OBJECTIVE: We explored the temporal relationship between changes in lung function and concentrations of plasma C-reactive protein (CRP) in a population-based cohort study at ages 14 and 20 years using a high-sensitivity CRP assay. METHODS: CRP measurements were performed in a total of 420 subjects at mean age of 13.9 years. Of these, 262 subjects (62%) participated in the follow-up investigation at mean age of 20.1 years. RESULTS: Levels of log-CRP at age 14 were not significantly associated with forced expiratory volume (FEV(1) ) or FEV(1) / forced vital capacity (FVC) ratio at age 20, nor with the change in FEV(1) , FVC or FEV(1) /FVC ratio between 14 and 20 years after controlling for body mass index (BMI), airway hyperresponsiveness (AHR), eosinophil cationic protein (ECP), asthma, smoking, sex, and height at 14 years, and change in height between 14 and 20 years. Sex, BMI, AHR, ECP and change in height between 14 and 20 years were identified as independent factors associated with the change in FEV(1) , FVC and FEV(1) /FVC ratio in adolescence. CONCLUSION: We did not find an association between CRP levels at age 14 and change in lung function by age 20; whereas, sex, change in height, BMI, AHR and ECP were associated with lung function change in adolescence. Our findings indicate that systemic inflammation is of less importance for change in lung function in adolescence. Please cite this paper as: Nybo M, Hansen HS, Siersted HC and Rasmussen F. No relationship between lung function and high-sensitive C-reactive protein in adolescence.

Recruitable collateral blood flow index predicts coronary instent restenosis after percutaneous coronary intervention.

AIMS: Collateral flow may influence long-term results after percutaneous coronary intervention (PCI) because of haemodynamic forces compete with the antegrade flow through the dilated lesion. The aim of the study was to assess the influence of recruitable collateral blood flow on restenosis in patients undergoing PCI with bare metal stents and using optimal antithrombotic treatment. METHODS AND RESULTS: In 95 patients, 95 de novo lesions were treated with PCI and a bare metal stent. Fractional flow reserve (FFR) at maximum hyperaemia induced by intravenous adenosine was determined. The pressure-derived collateral flow index (CFI) was determined as (P(w)-P(cvp))/(P(a)-P(cvp)), where P(w) represents coronary wedge pressure, P(cvp) central venous pressure, and P(a) mean aortic blood pressure. Both were measured during transient coronary occlusion by a balloon inflation of 30 s. Pre-interventional FFR (0.65 +/- 0.20) correlated inversely with the CFI (0.18 +/- 0.11), r =- 0.356, P < 0.001. After 9 months, binary angiographic restenosis (>/=50% diameter stenosis) was seen in 29.1%. Compared to patients with poorly developed collaterals (CFI < 0.25), patients with well-developed collaterals (CFI >/= 0.25) had a lower pre-interventional FFR (0.50 +/- 0.14 vs. 0.72 +/- 0.18, P < 0.001), a higher CFI (0.33 +/- 0.08 vs. 0.13 +/- 0.07, P < 0.001), and a higher binary restenosis rate (54.2% vs. 19.4, P = 0.003). CFI*100 was an independent predictor of restenosis after 9 months (odds ratio 1.07, 95% CI 1.02-1.12, P = 0.016). CONCLUSION: Recruitable collateral blood flow measured during balloon inflation predicts angiographic instent restenosis in PCI patients treated with bare metal stents.

High sensitive C-reactive protein and interleukin 6 are not related to neointimal hyperplasia in paclitaxel eluting stents or bare metal stents. An intravascular ultrasound study.

Implantation of coronary stents after percutaneous coronary intervention (PCI) may result in an inflammatory response with an increase in high sensitive C-reactive protein (Hs-CRP) and interleukin 6 (IL-6). In 25 patients Hs-CRP and IL-6 increased after coronary artery stenting, however, the increase in the inflammatory response did not differ between PES and BMS stents. The inflammatory response did not predict neointima hyperplasia measured by intravascular ultrasound after 6 months.