Hypoxic pulmonary vasoconstriction and nitric oxide

Hypoxia causes pulmonary vasoconstriction (HPV), improving oxygenation by redistribution of the pulmonary blood flow to better oxygenated lung regions. HPV is intrinsic to the pulmonary vascular smooth muscle cell, but can be modulated by several vasoactive substances, as for example endothelium derived nitric oxide (NO) and endothelin-1 (ET-1). A stimulus-response relationship between alveolar oxygen tension and pulmonary vascular resistance (PVR) has been observed in animals. The degree of hypoxia has also been shown to be of importance for endogenous NO production in the lung, but results are conflicting. We hypothesized that the fraction of inhaled oxygen (FIO2) is of importance for the active regulation of pulmonary vascular tone by hypoxia, NO and ET-1. We tested whether the strength of HPV in human lungs is related to FIO2 and if regional hypoxia influences the endogenous enzymatic and non-enzymatic production of NO in pig lungs, and circulating ETI levels in plasma in humans and pigs. We also studied the mechanism of action for inhaled NO (INO) in relation to hyperoxic and hypoxic lung regions in humans and pigs. The studies were conducted in anesthetized, lung-healthy patients or pigs, which were double-lumen intubated, enabling separate and synchronous mechanical ventilation of the right and left lung (Patients), or the left lower lobe (LLL) and the other lung regions (Pigs). Regional pulmonary blood flow was measured by inert gas elimination technique (Patients), or by ultrasonic flow probes (Pigs). We found a stimulus-response relationship between F102 and blood flow diversion, in the normal human lung. Exhaled NO concentration (NOE) from, and NO synthase (NOS) activity in hypoxic lung regions were significantly higher, than in hyperoxic lung regions. No significant changes were detected in plasma levels of ET-1-like immunoreactivity (ET-1-LI) during acute global or regional hypoxia. NOE was very low during NOS-blockade, but consistently higher in hypoxic than in hyperoxic lung regions. Infusion of nitrite during ongoing NOS-blockade increased NOE in a concentration-dependent manner, and much more in hypoxic than in hyperoxic lung regions. F102 was also shown to be of importance for the mechanism of action for NO. INO to hyperoxic lung regions, augmented the vaso-constriction in hypoxic lung regions, causing a further redistribution of pulmonary blood flow to hyperoxic lung regions in both Patients and Pigs. No such redistribution of pulmonary blood flow was observed in the absence of regional hypoxia. INO to hyperoxic lung regions, significantly decreased NOE from, and NOS activity in hypoxic lung regions, indicating a decreased endogenous enzymatic NO production in hypoxic lung regions. The mediator, or mediators causing this distant down-regulation of NO production was shown to be bloodborne, in a cross-circulation pig model. PVR increased and NOE decreased, predominantly in hypoxic lung regions, when pigs with regional LLL hypoxia received blood from pigs with INO, but not when they received blood from pigs without INO. Conclusions: A stimulus-response relationship exists between F102 and blood flow diversion in the healthy human lung. Acute hypoxia increases endogenous enzymatic NO production, but not ET- I -LI in plasma. Non-enzymatic NO production from nitrite can occur in hypoxic lung regions. INO has dual effects, dilating vessels in lung regions directly reached by INO, and constricting vessels in lung regions not directly reached by INO. This distant effect is blood-borne, and more prominent in hypoxic, than in hyperoxic lung regions

Repeated measures of body mass index and waist circumference in the assessment of mortality risk in patients with myocardial infarction

Aims: Weight loss is recommended for myocardial infarction (MI) patients with overweight or obesity. It has, however, been suggested that obese patients have better prognosis than normal-weight patients have, but also that central obesity is harmful. The aim of this study was to examine associations between repeated measures of body mass index (BMI) and waist circumference (WC), and all-cause mortality. Methods and results: A total of 14,224 MI patients aged <75 years in Sweden between the years 2004 and 2013 had measurements of risk factors at hospital discharge. The patients' BMI and WC were recorded in secondary prevention clinics two months and one year after hospital discharge. We collected mortality data up to 8.3 years after the last visit. There were 721 deaths. We used anthropometric measures at the two-month visit and the change from the two-month to the one-year visit. With adjustments for risk factors and the other anthropometric measure the hazard ratio (HR) per standard deviation in a Cox proportional hazard regression model for mortality was 0.64 (95% confidence interval [CI] 0.56-0.74) for BMI and 1.55 (95% CI 1.34-1.79) for WC, and 1.43 (95% CI 1.17-1.74) for a BMI decrease from month two to one year of more than 0.6 kg/m(2). Low BMI and high WC were associated with the highest mortality. Conclusion: High WC is harmful regardless of BMI in MI patients. Reduced BMI during the first year after MI is, however, associated with higher mortality, potentially being an indicator of deteriorated health

Changes in Physical Activity and Incidence of Nonfatal Cardiovascular Events in 47 153 Survivors of Myocardial Infarction.

Background The majority of patients survive the acute phase of myocardial infarction (MI) but have an increased risk of recurrent cardiovascular disease (CVD) events. To be regularly physically active or change activity level is associated with a lower risk of all-cause mortality. The objective was to explore to what extent physical activity (PA) levels or change in PA levels during the first year post-MI was associated with any recurrent nonfatal CVD events and specific CVD events (eg, MI, ischemic stroke, and vascular dementia). Methods and Results This cohort study among MI survivors was based on Swedish national registries between 2005 and 2020. PA levels were self-rated at 2 and 12 months post-MI, and patients were classified into remaining physically inactive, increasing, decreasing, or remaining active. A total of 6534 nonfatal CVD events occurred during 6 years of follow-up among the 47 153 included patients. In fully adjusted analyses, the risk of any nonfatal CVD event was lower (P<0.05) among patients remaining active (37%), increasing (22%), or decreasing (18%) PA level compared with remaining inactive. Compared with remaining inactive, the risk of recurring MI and stroke was lower (P>0.05) among remaining active (41% versus 52%, respectively), increasing (20% versus 35%, respectively), or decreasing PA level (24% versus 34%, respectively). For vascular dementia, patients remaining physically active had an 80% lower risk compared with remaining inactive (P<0.05). Conclusions Remaining physically active or change in PA levels during the first year post-MI was associated with a lower risk of recurrent nonfatal CVD events. This emphasizes the importance of supporting patients to continue to be or become physically active

High Self‐Reported Levels of Pain 1 Year After a Myocardial Infarction Are Related to Long‐Term All‐Cause Mortality: A SWEDEHEART Study Including 18 376 Patients

Background Pain increases the risk for cardiovascular diseases, including myocardial infarction (MI). However, the impact of pain on mortality after MI has not yet been investigated in large studies with long‐term follow‐up periods. Thus, we aimed to examine various levels of pain severity 1 year after an MI as a potential risk for all‐cause mortality. Methods and Results We collected data from 18 376 patients, aged <75 years, who had a registered MI event during the period from 2004 to 2013 and with measurements of potential cardiovascular risk indicators at hospital discharge from the Swedish quality register SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies). Self‐reported levels of experienced pain according to EuroQol‐5 dimension instrument were recorded in secondary prevention clinics 1 year after hospital discharge. We collected all‐cause mortality data up to 8.5 years (median, 3.4 years) after the 1‐year visit. The Cox proportional hazard regression was used to estimate hazard ratio (HR) and 95% CI. Moderate pain and extreme pain were reported by 38.2% and 4.5%, respectively, of included patients. There were 1067 deaths. Adjusted HR was 1.35 (95% CI, 1.18–1.55) and 2.06 (95% CI, 1.63–2.60) for moderate and extreme pain, respectively. Pain was a stronger mortality predictor than smoking. Conclusions Pain 1 year after MI is highly prevalent, and its effect on mortality 1 year after MI was found to be more pronounced than smoking. Clinicians managing patients after MI should recognize the need to consider experienced pain when making prognosis or treatment decisions

Predicted impact of lipid lowering therapy on cardiovascular and economic outcomes of Swedish atherosclerotic cardiovascular disease guideline

Background: The effects on cardiovascular disease (CVD) by treatment recommendations on prevention of atherosclerotic CVD remain to be evaluated. The objectives were to assess treatment gap for low density lipoprotein cholesterol (LDL-C) according to guidelines, potential impact on CVD outcomes, and possible avoided economic costs, in post myocardial infarction (MI) patients, if target LDL-C levels of &lt;= 1.8 mmol/L would be achieved. Methods: All patients registered in the Swedish Secondary Prevention after Heart Intensive care Admission register, with one-year post-MI follow-up during 2013 were selected. The REACH risk prediction and a calibrated model for recurrent cardiovascular events and death were used to estimate unadjusted risk prediction based on the REACH equation henceforth called base case, and calibrated CVD outcomes based on gender-specific risk factors. The predicted impact of the LDL-C reduction on the risk of CVD was based on the Cholesterol Treatment Trialists' Collaboration findings. Results: A sample of n = 5904 patients (74% men) with a mean age of 64 years were included. Around 70% did not reach LDL-C target = 1.8 mmol/L. Over a 10-year period, 820-2262 events were predicted to occur in those who did not reach target corresponding to 20%-55% risk of CVD events. To achieve LDL-C target, the mean LDL-C had to be reduced by 0.73 mmol/L (29%). If this LDL-C reduction was achieved, 195-544 life years, 132-343 CVD events, and 7.9-20.9 million Swedish crowns (MSEK) of direct costs, and 19.3-51.0 MSEK of total costs would be avoided. Conclusion: Lowering of LDL cholesterol to achieve target levels according to guidelines for post-MI patients may lead to fewer cardiovascular events and avoidance of event costs

Increased Physical Activity Post-Myocardial Infarction Is Related to Reduced Mortality; Results From the SWEDEHEART Registry

Background With increasing survival rates among patients with myocardial infarction (MI), more demands are placed on secondary prevention. While physical activity (PA) efforts to obtain a sufficient PA level are part of secondary preventive recommendations, it is still underutilized. Importantly, the effect of changes in PA after MI is largely unknown. Therefore, we sought to investigate the effect on survival from changes in PA level, post‐MI. Methods and Results Data from Swedish national registries were combined, totaling 22 227 patients with MI. PA level was self‐reported at 6 to 10 weeks post‐MI and 10 to 12 months post‐MI. Patients were classified as constantly inactive, increased activity, reduced activity, and constantly active. Proportional hazard ratios were calculated. During 100 502 person‐years of follow‐up (mean follow‐up time 4.2 years), a total of 1087 deaths were recorded. Controlling for important confounders (including left ventricular function, type of MI, medication, smoking, participation in cardiac rehabilitation program, quality of life, and estimated kidney function), we found lower mortality rates among constantly active (hazard ratio: 0.29, 95% confidence interval: 0.21–0.41), those with increased activity (0.41, 95% confidence interval: 0.31–0.55), and those with reduced activity (hazard ratio: 0.56, 95% confidence interval: 0.45–0.69) during the first year post‐MI, compared with those being constantly inactive. Stratified analyses indicated strong effect of PA level among both sexes, across age, MI type, kidney function, medication, and smoking status. Conclusions The present article shows that increasing the PA level, compared with staying inactive the first year post‐MI, was related to reduced mortality.Ischemisk hjärtsjukdo

Target-Attainment Rates of Low-Density Lipoprotein Cholesterol Using Lipid-Lowering Drugs One Year After Acute Myocardial Infarction in Sweden

The objective of this prospective cohort study was to describe real-life use of lipid-lowering drugs and low-density lipoprotein cholesterol (LDL-C) target-attainment rates 1 year after acute myocardial infarction (AMI). LDL-C was recorded at hospital admission for AMI and at follow-up at 2 and 12 months after AMI in 17,236 patients in the Swedish heart registry, SWEDEHEART, from 2004 through 2009. Lipid-lowering treatments were identified using the Swedish Prescribed Drug Register. More than 90% of patients received statins after ANT. Simvastatin 40%) was prescribed for 8.4%, 11.9%, and 12.2% at these time points, and combinations of statin/ezetimibe for 1.1%, 2.8%, and 5.0%, respectively. The LDL-C target of <2.5 mmol/L (97 mg/dl) was achieved in 74.5% of patients at 2 months and 72.3% at 12 months after AMI. Treatment was intensified for only 21.3% of patients with LDL-C above target at 2 months. In multivariate analysis, higher LDL-C levels at admission and at 2 months correlated to increased risk for under treatment at 12 months after AMI. In conclusion, statin treatment after AMI in Sweden has become standard, but titration to reach recommended LDL-C levels is still suboptimal. Strategies to further improve implementation of guidelines are needed. (C) 2014 Elsevier Inc. All rights reserved

Impact on long-term mortality of presence of obstructive coronary artery disease and classification of myocardial infarction.

In contrast to the associated with thromboembolic event type 1 myocardial infarction, type 2 myocardial infarction is caused by acute imbalance between oxygen supply and demand of myocardium. Type 2 myocardial infarction may be present in patients with or without obstructive coronary artery disease, but knowledge about patient characteristics, treatments, and outcome in relation to coronary artery status is lacking. We aimed to compare background characteristics, triggering mechanisms, treatment and long-term prognosis in large real-life cohort of patients with type 1 and type 2 myocardial infarction with and without obstructive coronary artery disease

Physical inactivity and smoking after myocardial infarction as predictors for readmission and survival : results from the SWEDEHEART-registry.

BACKGROUND: Physical activity (PA) and smoking cessation are included in the secondary prevention guidelines after myocardial infarction (MI), but they are still underutilised. This study aims to explore how PA level and smoking status (6-10 weeks post-MI) were associated with 1-year readmission and mortality during full follow-up time, and with the cumulative 5-year mortality. METHODS: A population-based cohort of all hospitals providing MI-care in Sweden (SWEDEHEART-registry) in 2004-2014. PA was expressed as the number of exercise sessions of ≥ 30 min in the last 7 days: 0-1 (low), 2-4 (medium) and 5-7 (high) sessions/week. Individuals were categorised as smokers, former smokers or never-smokers. The associations were analysed by unadjusted and adjusted logistic and Cox regressions. RESULTS: During follow-up (M = 3.58 years), a total of 1702 deaths occurred among 30 644 individuals (14.1 cases per 1000 person-years). For medium and high PA, the hazard ratios (HRs) for mortality were 0.39 and 0.36, respectively, compared with low PA. For never-smokers, the HR was 0.45 and former smokers 0.56 compared with smokers. Compared with low PA, the odds ratios (ORs) for readmission in medium PA were 0.65 and 0.59 for CVD and non-CVD causes, respectively. For high PA, the corresponding ORs were 0.63 and 0.55. The association remained in adjusted models. There were no associations between smoking status and readmission. CONCLUSIONS: The PA level and smoking status are strong predictors of mortality post-MI and the PA level also predicts readmission, highlighting the importance of adherence to the secondary prevention guidelines