Tomas Jernberg

N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation☆

OBJECTIVES The study evaluated the prognostic value of single measurement of N-terminal pro brain natriuretic peptide (NT-proBNP) obtained on admission in patients with symptoms suggestive of an acute coronary syndrome and no ST-segment elevation. BACKGROUND Patients with symptoms suggestive of an acute coronary syndrome and no ST-segment elevation constitute a large and heterogeneous population. Early risk stratification has been based on clinical background factors, electrocardiography (ECG) and biochemical markers of myocardial damage. The neurohormonal activation has, so far, received less attention. METHODS The NT-proBNP was analyzed on admission in 755 patients admitted because of chest pain and no ST-segment elevation. Patients were followed concerning death for 40 months (median). RESULTS The median NT-proBNP level was 400 (111 to 1646) ng/l. Compared to the lowest quartile, patients in the second, third and fourth quartiles had a relative risk of subsequent death of 4.2 (1.6 to 11.1), 10.7 (4.2 to 26.8) and 26.6 (10.8 to 65.5), respectively. When NT-proBNP was added to a Cox regression model including clinical background factors, ECG and troponin T, the NT-proBNP levels were independently associated with prognosis. CONCLUSIONS A single measurement of NT-proBNP on admission will substantially improve the early risk stratification of patients with symptoms suggestive of an acute coronary syndrome and no ST-segment elevation. A combination of clinical background factors, ECG, troponin T and NT-proBNP obtained on admission will provide a highly discerning tool for risk stratification and further clinical decisions.

Troponin elevation in coronary vs. non-coronary disease

Acute myocardial infarction is defined as myocardial cell death due to prolonged myocardial ischaemia. Cardiac troponins (cTn) are the most sensitive and specific biochemical markers of myocardial injury and with the new high-sensitivity troponin methods very minor damages on the heart muscle can be detected. However, elevated cTn levels indicate cardiac injury, but do not define the cause of the injury. Thus, cTn elevations are common in many disease states and do not necessarily indicate the presence of a thrombotic acute coronary syndrome (ACS). In the clinical work it may be difficult to interpret dynamic changes of troponin in conditions such as stroke, pulmonary embolism, sepsis, acute perimyocarditis, Tako-tsubo, acute heart failure, and tachycardia. There are no guidelines to treat patients with elevated cTn levels and no coronary disease. The current strategy of treatment of patients with elevated troponin and non-acute coronary syndrome involves treating the underlying causes. The aim of this paper is to review data from studies of non-ACS patients with acutely elevated troponin who in clinical practice may be difficult to discriminate from ACS patients.

The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)

Aims The aims of the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) are to support the improvement of care and evidence-based development of therapy of coronary artery disease (CAD). Interventions To provide users with online interactive reports monitoring the processes of care and outcomes and allowing direct comparisons over time and with other hospitals. National, regional and county-based reports are publicly presented on a yearly basis. Setting Every hospital (n=74) in Sweden providing the relevant services participates. Launched in 2009 after merging four national registries on CAD. Population Consecutive acute coronary syndrome (ACS) patients, and patients undergoing coronary angiography/angioplasty or heart surgery. Includes approximately 80 000 new cases each year. Startpoints On admission in ACS patients, at coronary angiography in patients with stable CAD. Baseline data 106 variables for patients with ACS, another 75 variables regarding secondary prevention after 12–14 months, 150 variables for patients undergoing coronary angiography/angioplasty, 100 variables for patients undergoing heart surgery. Data capture Web-based registry with all data registered online directly by the caregiver. Data quality A monitor visits approximately 20 hospitals each year. In 2007, there was a 96% agreement. Endpoints and linkages to other data Merged with the National Cause of Death Register, including information about vital status of all Swedish citizens, the National Patient Registry, containing diagnoses at discharge for all hospital stays in Sweden and the National Registry of Drug prescriptions recording all drug prescriptions in Sweden. Access to data Available for research by application to the SWEDEHEART steering group.

Association Between Adoption of Evidence-Based Treatment and Survival for Patients With ST-Elevation Myocardial Infarction

CONTEXT Only limited information is available on the speed of implementation of new evidence-based and guideline-recommended treatments and its association with survival in real life health care of patients with ST-elevation myocardial infarction (STEMI). OBJECTIVE To describe the adoption of new treatments and the related chances of short- and long-term survival in consecutive patients with STEMI in a single country over a 12-year period. DESIGN, SETTING, AND PARTICIPANTS The Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA) records baseline characteristics, treatments, and outcome of consecutive patients with acute coronary syndrome admitted to almost all hospitals in Sweden. This study includes 61,238 patients with a first-time diagnosis of STEMI between 1996 and 2007. MAIN OUTCOME MEASURES Estimated and crude proportions of patients treated with different medications and invasive procedures and mortality over time. RESULTS Of evidence-based treatments, reperfusion increased from 66% (95%, confidence interval [CI], 52%-79%) to 79% (95% CI, 69%-89%; P < .001), primary percutaneous coronary intervention from 12% (95% CI, 11%-14%) to 61% (95% CI, 45%-77%; P < .001), and revascularization from 10% (96% CI, 6%-14%) to 84% (95% CI, 73%-95%; P < .001). The use of aspirin, clopidogrel, β-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors all increased: clopidogrel from 0% to 82% (95% CI, 69%-95%; P < .001), statins from 23% (95% CI, 12%-33%) to 83% (95% CI, 75%-91%; P < .001), and ACE inhibitor or angiotensin II receptor blockers from 39% (95% CI, 26%-52%) to 69% (95% CI, 58%-70%; P < .001). The estimated in-hospital, 30-day and 1-year mortality decreased from 12.5% (95% CI, 4.3%-20.6%) to 7.2% (95% CI, 1.7%-12.6%; P < .001); from 15.0% (95% CI, 6.2%-23.7%) to 8.6% (95% CI, 2.7%-14.5%; P < .001); and from 21.0% (95% CI, 11.0%-30.9%) to 13.3% (95% CI, 6.0%-20.4%; P < .001), respectively. After adjustment, there was still a consistent trend with lower standardized mortality over the years. The 12-year survival analyses showed that the decrease of mortality was sustained over time. CONCLUSION In a Swedish registry of patients with STEMI, between 1996 and 2007, there was an increase in the prevalence of evidence-based treatments. During this same time, there was a decrease in 30-day and 1-year mortality that was sustained during long-term follow-up.

Cystatin C A Novel Predictor of Outcome in Suspected or Confirmed Non–ST-Elevation Acute Coronary Syndrome

Background—Patients with suspected or confirmed non–ST-elevation acute coronary syndrome (ACS) constitute a large and heterogeneous group. Measurements of renal function such as serum creatinine and estimation of creatinine clearance carry independent prognostic information in this population. Cystatin C is a new and better marker of renal function than creatinine. The aim was therefore to evaluate the prognostic value of cystatin C in this population. Methods and Results—Cystatin C was analyzed on admission in 726 patients admitted because of symptoms suggestive of an acute coronary syndrome and no ST-segment elevations. Patients were followed up with regard to death and myocardial infarction for a median of 40 and 6 months, respectively. The median cystatin C level was 1.00 mg/L (25th to 75th percentile, 0.83 to 1.24 mg/L). The risk of death during follow-up increased with increasing levels of cystatin C. In the group with non–ST-elevation ACS, patients in the second, third, and fourth quartiles had a relative risk of subsequent death of 1.8 (95% CI, 0.6 to 5.3), 3.2 (95% CI, 1.2 to 8.5), and 11.7 (95% CI, 4.7 to 29.3) compared with the lowest quartile. In Cox regression models including well-known predictors of outcome, cystatin C level was independently associated with mortality but not with the risk of subsequent myocardial infarction. In a comparison of the markers of renal function in receiver-operating curve analyses, cystatin C had the best ability to discriminate between survivors and nonsurvivors. Conclusions—A single measurement of cystatin C will substantially improve the early risk stratification of patients with suspected or confirmed non–ST-elevation ACS.

Protein gene product 9.5-immunoreactive nerve fibres and cells in human skin.

SummarySections of human skin were processed according to the indirect immunofluorescence technique with a rabbit antiserum against human protein gene product 9.5 (PGP 9.5). Immunoreactivity was detected in intraepidermal and dermal nerve fibres and cells. The intraepidermal nerves were varicose or smooth with different diameters, running as single processes or branched, straight or bent, projecting in various directions and terminating in the stratum basale, spinosum or granulosum. The density of the intraepidermal nerves varied between the different skin areas investigated. PGP 9.5-containing axons of the lower dermis were found in large bundles. They separated into smaller axon bundles within the upper dermis, entering this portion of the skin perpendicular to the surface. Then they branched into fibres mainly arranged parallel to the epidermal-dermal junctional zone. However, the fibres en route to the epidermis traversed the upper dermis more or less perpendicularly. Furthermore, immunoreactive dermal nerve fibres were found in the Meissner corpuscles, the arrector pili muscles, hair follicles, around the eccrine and apocrine sweat glands and around certain blood vessels. Such fibres were also observed around most subcutaneous blood vessels, sometimes heavily innervating these structures. Numerous weakly-to-strongly PGP 9.5-immunoreactive cells were found both in the epidermis and in the dermis.

Cardiovascular risk in post-myocardial infarction patients : nationwide real world data demonstrate the importance of a long-term perspective.

AIMS Long-term disease progression following myocardial infarction (MI) is not well understood. We examined the risk of subsequent cardiovascular events in patients discharged after MI in Sweden. METHODS AND RESULTS This was a retrospective, cohort study linking morbidity, mortality, and medication data from Swedish national registries. Of 108 315 patients admitted to hospital with a primary MI between 1 July 2006 and 30 June 2011 (index MI), 97 254 (89.8%) were alive 1 week after discharge and included in this study. The primary composite endpoint of risk for non-fatal MI, non-fatal stroke, or cardiovascular death was estimated for the first 365 days post-index MI and Day 366 to study completion. Risk and risk factors were assessed by Kaplan-Meier analysis and Cox proportional hazards modelling, respectively. Composite endpoint risk was 18.3% during the first 365 days post-index MI. Age [60-69 vs. <60 years: HR (95% CI): 1.37 (1.30-1.45); 70-79 vs. <60 years: 2.13 (2.03-2.24); >80 vs. <60 years: 3.96 (3.78-4.15)], prior MI [1.44 (1.40-1.49)], stroke [1.49 (1.44-1.54)], diabetes [1.37 (1.34-1.40)], heart failure [1.57 (1.53-1.62)] and no index MI revascularisation [1.88 (1.83-1.93)] were each independently associated with a higher risk of ischaemic events or death. For patients without a combined endpoint event during the first 365 days, composite endpoint risk was 20.0% in the following 36 months. CONCLUSIONS Risk of cardiovascular events appeared high beyond the first year post-MI, indicating a need for prolonged surveillance, particularly in patients with additional risk factors.

Influence of Renal Function on the Effects of Early Revascularization in Non-ST-Elevation Myocardial Infarction Data From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)

Background— It is unknown whether patients with non–ST-elevation myocardial infarction derive a similar benefit from an early invasive therapy at different levels of renal function. Methods and Results— A total of 23 262 consecutive non–ST-elevation myocardial infarction patients ≤80 years old were included in a nationwide coronary care unit register between 2003 and 2006. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease Study formula. Patients were divided into medically or invasively treated groups if revascularized within 14 days of admission. A propensity score for the likelihood of invasive therapy was calculated. A Cox regression model with adjustment for propensity score and discharge medication was used to assess the association between early revascularization and 1-year mortality across renal function stages. There was a gradient, with significantly fewer patients treated invasively with declining renal function: eGFR ≥90 mL · min−1 · 1.73 m−2, 62%; eGFR 60 to 89 mL · min−1 · 1.73 m−2, 55%; eGFR 30 to 59 mL · min−1 · 1.73 m−2, 36%; eGFR 15 to 29 mL · min−1 · 1.73 m−2, 14%; and eGFR <15 mL · min−1 · 1.73 m−2/dialysis, 15% (P<0.001). After adjustment, the overall 1-year mortality was 36% lower (hazard ratio 0.64, 95% confidence interval 0.56 to 0.73, P<0.001) with an invasive strategy. The magnitude of survival difference was similar in normal-to-moderate renal function groups. The lower mortality observed with invasive therapy declined with lower renal function, with no difference in mortality in patients with kidney failure (eGFR <15 mL · min−1 · 1.73 m−2) or in those receiving dialysis (hazard ratio 1.61, 95% confidence interval 0.84 to 3.09, P=0.15). Conclusions— Early invasive therapy is associated with greater 1-year survival in patients with non–ST-elevation myocardial infarction and mild-to-moderate renal insufficiency, but the benefit declines with lower renal function, and is less certain in those with renal failure or on dialysis.

Stress Reduction Prolongs Life in Women With Coronary Disease The Stockholm Women's Intervention Trial for Coronary Heart Disease (SWITCHD)

Background—Psychosocial stress may increase risk and worsen prognosis of coronary heart disease in women. Interventions that counteract women’s psychosocial stress have not previously been presented. This study implemented a stress reduction program for women and investigated its ability to improve survival in women coronary patients. Methods and Results—Two hundred thirty-seven consecutive women patients, aged 75 years or younger, hospitalized for acute myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention were randomized to a group-based psychosocial intervention program or usual care. Initiated 4 months after hospitalization, intervention groups of 4 to 8 women met for a total of 20 sessions that were spread over a year. We provided education about risk factors, relaxation training techniques, methods for self-monitoring and cognitive restructuring, with an emphasis on coping with stress exposure from family and work, and self-care and compliance with clinical advice. From randomization until end of follow-up (mean duration, 7.1 years), 25 women (20%) in the usual care and 8 women (7%) in the stress reduction died, yielding an almost 3-fold protective effect of the intervention (odds ratio, 0.33; 95% CI, 0.15 to 0.74; P=0.007). Introducing baseline measures of clinical prognostic factors, including use of aspirin, &bgr;-blockers, angiotensin-converting enzyme inhibitors, calcium-channel blockers, and statins into multivariate models confirmed the unadjusted results (P=0.009). Conclusions—Although mechanisms remain unclear, a group-based psychosocial intervention program for women with coronary heart disease may prolong lives independent of other prognostic factors.

N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease.

OBJECTIVES We sought to examine whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), in addition to cardiac troponin T (cTnT) and interleukin-6 (IL-6), improve the ability to identify high-risk patients who benefit from an early invasive strategy. BACKGROUND Biochemical indicators of cardiac performance (e.g., NT-proBNP), inflammation (e.g., IL-6), and myocardial damage (e.g., cTnT) predict mortality in unstable coronary artery disease (UCAD) (i.e., unstable angina or non-ST-segment elevation myocardial infarction [MI]). In these patients, an early invasive treatment strategy improves the outcome. METHODS Levels of NT-proBNP, cTnT, and IL-6 were measured in 2,019 patients with UCAD randomized to an invasive or non-invasive strategy in the FRagmin and fast revascularization during InStability in Coronary artery disease (FRISC-II) trial. Patients were followed up for two years to determine death and MI. RESULTS Patients in the third NT-proBNP tertile had a 4.1-fold (95% confidence interval [CI] 2.4 to 7.2) and 3.5-fold (95% CI 1.8 to 6.8) increased mortality in the non-invasive and invasive groups, respectively. An increased NT-proBNP level was independently associated with mortality. In patients with increased levels of both NT-proBNP and IL-6, an early invasive strategy reduced mortality by 7.3% (risk ratio 0.46, 95% CI 0.21 to 1.00). In patients with lower NT-proBNP or IL-6 levels, the mortality was not reduced. Only elevated cTnT was independently associated with future MI and a reduction of MI by means of an invasive strategy. CONCLUSIONS N-terminal proBNP is independently associated with mortality. The combination of NT-proBNP and IL-6 seems to be a useful tool in the identification of patients with a definite survival benefit from an early invasive strategy. Only cTnT is independently associated with future MI and a reduction of MI by an invasive strategy.