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Background Receptor selectivity of sodium-glucose cotransporter-2 inhibitors (SGLT2i) varies greatly between agents. The overall improvement of cardiovascular (CV) outcomes in heart failure (HF) patients varies between trials. We, therefore, evaluated the comparative efficacy of individual SGLT2i and the influence of their respective receptor selectivity thereon. Methods We identified randomized controlled trials investigating the use of SGLT2i in patients with HF—either as the target cohort or as a subgroup of it. Comparators included placebo or any other active treatment. The primary endpoint was the composite of hospitalization for HF or CV death. Secondary outcomes included all-cause mortality, CV mortality, hospitalization for HF, worsening renal function (RF), and the composite of worsening RF or CV death. Evidence was synthesized using network meta-analysis. In addition, the impact of receptor selectivity on outcomes was analysed using meta-regression. Results We identified 18,265 patients included in 22 trials. Compared to placebo, selective and non-selective SGLT2i improved fatal and non-fatal HF events. Head-to-head comparisons suggest superior efficacy with sotagliflozin as compared to dapagliflozin, empagliflozin or ertugliflozin. No significant difference was found between canagliflozin and sotagliflozin. Meta-regression analyses show a decreasing benefit on HF events with increasing receptor selectivity of SGLT2i. In contrast, receptor selectivity did not affect mortality and renal endpoints and no significant difference between individual SGLT2i was noted. Conclusion Our data point towards a class-effect of SGLT2i on mortality and renal outcomes. However, non-selective SGLT2i such as sotagliflozin may be superior to highly selective SGLT2i in terms of HF outcomes.

Background Subjects with chronic obstructive pulmonary disease (COPD) are prone to accelerated decay of muscle strength and mass with advancing age. This is believed to be driven by disease-inherent systemic pathophysiologies, which are also assumed to drive muscle cells into a state of anabolic resistance, leading to impaired abilities to adapt to resistance exercise training. Currently, this phenomenon remains largely unstudied. In this study, we aimed to investigate the assumed negative effects of COPD for health- and muscle-related responsiveness to resistance training using a healthy control-based translational approach. Methods Subjects with COPD (n = 20, GOLD II-III, FEV1predicted 57 ± 11%, age 69 ± 5) and healthy controls (Healthy, n = 58, FEV1predicted 112 ± 16%, age 67 ± 4) conducted identical whole-body resistance training interventions for 13 weeks, consisting of two weekly supervised training sessions. Leg exercises were performed unilaterally, with one leg conducting high-load training (10RM) and the contralateral leg conducting low-load training (30RM). Measurements included muscle strength (nvariables = 7), endurance performance (nvariables = 6), muscle mass (nvariables = 3), muscle quality, muscle biology (m. vastus lateralis; muscle fiber characteristics, RNA content including transcriptome) and health variables (body composition, blood). For core outcome domains, weighted combined factors were calculated from the range of singular assessments. Results COPD displayed well-known pathophysiologies at baseline, including elevated levels of systemic low-grade inflammation ([c-reactive protein]serum), reduced muscle mass and functionality, and muscle biological aberrancies. Despite this, resistance training led to improved lower-limb muscle strength (15 ± 8%), muscle mass (7 ± 5%), muscle quality (8 ± 8%) and lower-limb/whole-body endurance performance (26 ± 12%/8 ± 9%) in COPD, resembling or exceeding responses in Healthy, measured in both relative and numeric change terms. Within the COPD cluster, lower FEV1predicted was associated with larger numeric and relative increases in muscle mass and superior relative improvements in maximal muscle strength. This was accompanied by similar changes in hallmarks of muscle biology such as rRNA-content↑, muscle fiber cross-sectional area↑, type IIX proportions↓, and changes in mRNA transcriptomics. Neither of the core outcome domains were differentially affected by resistance training load. Conclusions COPD showed hitherto largely unrecognized responsiveness to resistance training, rejecting the notion of disease-related impairments and rather advocating such training as a potent measure to relieve pathophysiologies. Trial registration: ClinicalTrials.gov ID: NCT02598830. Registered November 6th 2015, https://clinicaltrials.gov/ct2/show/NCT02598830

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes mellitus (T2D). The comparative efficacy of individual SGLT2i remains unclear. We searched PubMed, www.clinicaltrials.gov and the Cochrane Central Register of Controlled Trials for randomised controlled trials exploring the use of canagliflozin, dapagliflozin, empagliflozin or ertugliflozin in patients with T2D. Comparators included placebo or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality and worsening heart failure (HF). Evidence was synthesised using network meta-analysis (NMA). Sixty-four trials reporting on 74,874 patients were included. The overall quality of evidence was high. When compared with placebo, empagliflozin and canagliflozin improved all three endpoints, whereas dapagliflozin improved worsening HF. When compared with other SGLT2i, empagliflozin was superior for all-cause and cardiovascular mortality reduction. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Ertugliflozin had no effect on any of the three endpoints investigated. Sensitivity analyses including extension periods of trials or excluding studies with a treatment duration of n = 38,719). Empagliflozin and canagliflozin improved survival with empagliflozin being superior to the other SGLT2i. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Prospective head-to-head comparisons would be needed to confirm these results.

Aims:\ud \ud Beta-blockers are recommended for the treatment of chronic heart failure (CHF). However, it is disputed whether beta-blockers exert a class effect or whether there are differences in efficacy between agents.\ud \ud Methods and results:\ud \ud 6010 out-patients with stable CHF and a reduced left ventricular ejection fraction prescribed either bisoprolol, carvedilol or metoprolol succinate were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and the respective propensity scores for beta-blocker treatment. During a follow-up of 26,963 patient-years, 302 (29.5%), 637 (37.0%), and 1232 (37.7%) patients died amongst those prescribed bisoprolol, carvedilol, and metoprolol, respectively. In univariable analysis of the general sample, bisoprolol and carvedilol were both associated with lower mortality as compared with metoprolol succinate (HR 0.80, 95% CI 0.71–0.91, p < 0.01, and HR 0.86, 95% CI 0.78–0.94, p < 0.01, respectively). Patients prescribed bisoprolol or carvedilol had similar mortality (HR 0.94, 95% CI 0.82–1.08, p = 0.37). However, there was no significant association between beta-blocker choice and all-cause mortality in any of the matched samples (HR 0.90; 95% CI 0.76–1.06; p = 0.20; HR 1.10, 95% CI 0.93–1.31, p = 0.24; and HR 1.08, 95% CI 0.95–1.22, p = 0.26 for bisoprolol vs. carvedilol, bisoprolol vs. metoprolol succinate, and carvedilol vs. metoprolol succinate, respectively). Results were confirmed in a number of important subgroups.\ud \ud Conclusion:\ud \ud Our results suggest that the three beta-blockers investigated have similar effects on mortality amongst patients with CHF.

Background/Aims: Spironolactone may be hazardous in heart failure (HF) patients with renal dysfunction due to risk of hyperkalemia and worsened renal function. We aimed to evaluate the effect of spironolactone on all-cause mortality in HF outpatients with renal dysfunction in a propensity-score-matched study. Methods: A total of 2,077 patients from the Norwegian Heart Failure Registry with renal dysfunction (eGFR 2) not treated with spironolactone at the first visit at the HF clinic were eligible for the study. Patients started on spironolactone at the outpatient HF clinics (n = 206) were propensity-score-matched 1:1 with patients not started on spironolactone, based on 16 measured baseline characteristics. Kaplan-Meier and Cox regression analyses were used to investigate the independent effect of spironolactone on 2-year all-cause mortality. Results: Propensity score matching identified 170 pairs of patients, one group receiving spironolactone and the other not. The two groups were well matched (mean age 76.7 ± 8.1 years, 66.4% males, and eGFR 46.2 ± 10.2 mL/min/1.73 m2). Treatment with spironolactone was associated with increased potassium (delta potassium 0.31 ± 0.55 vs. 0.05 ± 0.41 mmol/L, p < 0.001) and decreased eGFR (delta eGFR -4.12 ± 12.2 vs. -0.98 ± 7.88 mL/min/1.73 m2, p = 0.006) compared to the non-spironolactone group. After 2 years, 84% of patients were alive in the spironolactone group and 73% of patients in the non-spironolactone group (HR 0.59, 95% CI 0.37-0.92, p = 0.020). Conclusion: In HF outpatients with renal dysfunction, treatment with spironolactone was associated with improved 2-year survival compared to well-matched patients not treated with spironolactone. Favorable survival was observed despite worsened renal function and increased potassium in the spironolactone group.

Tager, T., et al. (2019). "Comparative effectiveness of loop diuretics on mortality in the treatment of patients with chronic heart failure - A multicenter propensity score matched analysis." Int J Cardiol 289: 83-90. Abstract BACKGROUND: Loop diuretics are given to the majority of patients with chronic heart failure (HF). Whether the different pharmacological properties of the three guideline-recommended loop diuretics result in differential effects on survival is unknown. METHODS: 6293 patients with chronic HF using either bumetanide, furosemide or torasemide were identified in three European HF registries. Patients were individually matched on both the respective propensity scores for receipt of the individual drug and dose-equivalents thereof. RESULTS: During a follow-up of 35,038 patient-years, 652 (53.7%), 2179 (51.9%), and 268 (30.4%) patients died amongst those prescribed bumetanide, furosemide, and torasemide, respectively. In univariable analyses of the general sample, bumetanide and furosemide were both associated with higher mortality as compared with torasemide treatment (HR 1.50, 95% CI 1.31-1.73, p

ObjectiveTo describe the epidemiology, long-term outcomes and temporal trends in mortality in ambulatory patients with chronic heart failure (HF) with reduced (HFrEF), mid-range (HFmrEF) or preserved ejection fraction (HFpEF) from three European countries.MethodsWe identified 10 312 patients from the Norwegian HF Registry and the HF registries of the universities of Heidelberg, Germany, and Hull, UK. Patients were classified according to baseline left ventricular ejection fraction (LVEF) and time of enrolment (period 1: 1995–2005 vs period 2: 2006–2015). Predictors of mortality were analysed by use of univariable and multivariable Cox regression analyses.ResultsAmong 10 312 patients with stable HF, 7080 (68.7%), 2086 (20.2%) and 1146 (11.1%) were classified as having HFrEF, HFmrEF or HFpEF, respectively. A total of 4617 (44.8%) patients were included in period 1, and 5695 (55.2%) patients were included in period 2. Baseline characteristics significantly differed with respect to type of HF and time of enrolment. During a median follow-up of 66 (33–105) months, 5297 patients (51.4%) died. In multivariable analyses, survival was independent of LVEF category (p>0.05), while mortality was lower in period 2 as compared with period 1 (HR 0.81, 95% CI 0.72 to 0.91, pConclusionAmbulatory patients with HF stratified by LVEF represent different phenotypes. However, after adjusting for a wide range of covariates, long-term survival is independent of LVEF category. Outcome significantly improved during the last two decades irrespective from type of HF.

Background Elevated serum uric acid (SUA) is associated with poor prognosis in patients with cardiovascular disease, yet it is still not decided whether the role of SUA is causal or only reflects an underlying disease. The purpose of the study was to investigate if SUA was an independent predictor of 5-year all-cause mortality in a propensity score matched cohort of chronic heart failure (HF) outpatients. Furthermore, to assess whether gender or renal function modified the effect of SUA. Methods Patients (n = 4684) from the Norwegian Heart Failure Registry with baseline SUA were included in the study. Individuals in the highest gender-specific SUA quartile were propensity score matched 1:1 with patients in the lowest three SUA quartiles. The propensity score matching procedure created 928 pairs of patients (73.4% males, mean age 71.4 ± 11.5 years) with comparable baseline characteristics. Kaplan Meier and Cox regression analyses were used to investigate the independent effect of SUA on all-cause mortality. Results SUA in the highest quartile was an independent predictor of all-cause mortality in HF outpatients (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.03–1.37, p-value 0.021). Gender was found to interact the relationship between SUA and all-cause mortality (p-value for interaction 0.007). High SUA was an independent predictor of all-cause mortality in women (HR 1.65, 95% CI 1.24–2.20, p-value 0.001), but not in men (HR 1.06, 95% CI 0.89–1.25, p-value 0.527). Renal function did not influence the relationship between SUA and all-cause mortality (p-value for interaction 0.539). Conclusions High SUA was independently associated with inferior 5-year survival in Norwegian HF outpatients. The finding was modified by gender and high SUA was only an independent predictor of 5-year all-cause mortality in women, not in men.

Objectives: Heart failure (HF) patients with diabetes mellitus experience poor prognosis. We assessed the independent predictive effect of prevalent diabetes mellitus on all-cause mortality in HF outpatients. Furthermore, we investigated if optimized HF medication differed in diabetic versus nondiabetic patients. Methods: From 6,289 patients included in the Norwegian HF registry during 2000-2012, 724 diabetic HF outpatients were propensity-score-matched with nondiabetic HF outpatients (1:1), based on 21 measured baseline variables. Baseline characteristics, measured comorbidities and medication were balanced in the matched sample. Results: Diabetes was not an independent predictor of all-cause mortality in the propensity-matched analyses (hazard ratio 1.041; 95% confidence interval 0.875-1.240). No interactions were found between the prognostic impact of diabetes and the strata renal function, systolic function or etiology of chronic HF. Diabetic HF outpatients were independently prescribed higher doses of β-blockers and loop diuretics (both p < 0.001) and were more prone to receive statins (p = 0.003) than nondiabetics. Conclusions: Prevalent diabetes mellitus was not an independent predictor of all-cause mortality in HF outpatients. Explanations other than tight glycemic control should be assessed to improve the prognosis of diabetic HF outpatients. The more intensive, optimized HF medication for diabetic HF outpatients may, to a certain degree, explain our results.

Background— β-Blockers exert a prognostic benefit in the treatment of chronic heart failure. Their pharmacological properties vary. The only substantial comparative trial to date—the Carvedilol or Metoprolol European Trial—has compared carvedilol with short-acting metoprolol tartrate at different dose equivalents. We therefore addressed the relative efficacy of equal doses of carvedilol and metoprolol succinate on survival in multicenter hospital outpatients with chronic heart failure. Methods and Results— Four thousand sixteen patients with stable systolic chronic heart failure who were using either carvedilol or metoprolol succinate were identified in the Norwegian Heart Failure Registry and The Heart Failure Registry of the University of Heidelberg, Germany. Patients were individually matched on both the dose equivalents and the respective propensity scores for β-blocker treatment. During a follow-up for 17 672 patient-years, it was found that 304 (27.2%) patients died in the carvedilol group and 1066 (36.8%) in the metoprolol group. In a univariable analysis of the general sample, metoprolol therapy was associated with higher mortality compared with carvedilol therapy (hazard ratio, 1.49; 95% confidence interval, 1.31–1.69; P P =0.75) and adjustment for propensity score and dose equivalents (hazard ratio, 1.06; 95% confidence interval, 0.94–1.20; P =0.36) or in the propensity and dose equivalent–matched sample (hazard ratio, 1.00; 95% confidence interval, 0.82–1.23; P =0.99). These results were essentially unchanged for all prespecified subgroups. Conclusions— In outpatients with chronic heart failure, no conclusive association between all-cause mortality and treatment with carvedilol or metoprolol succinate was observed after either multivariable adjustment or multilevel propensity score matching.

Background:\ud \ud In patients with chronic heart failure (CHF) increasing levels of total serum cholesterol are associated with improved survival – while statin usage is not. The impact of statin treatment on the “reverse epidemiology” of cholesterol is unclear.\ud \ud Methods:\ud \ud 2992 consecutive patients with non-ischemic CHF due to left ventricular systolic dysfunction from the Norwegian CHF Registry and the CHF Registries of the Universities of Hull, UK, and Heidelberg, Germany, were studied. 1736 patients were individually double-matched on both cholesterol levels and the individual propensity scores for statin treatment. All-cause mortality was analyzed as a function of baseline cholesterol and statin use in both the general and the matched sample.\ud \ud Results:\ud \ud 1209 patients (40.4%) received a statin. During a follow-up of 13,740 patient-years, 360 statin users (29.8%) and 573 (32.1%) statin non-users died. When grouped according to total cholesterol levels as low (≤ 3.6 mmol/L), moderate (3.7–4.9 mmol/L), high (4.8–6.2 mmol/L), and very high (> 6.2 mmol/L), we found improved survival with very high as compared with low cholesterol levels. This association was present in statin users and non-users in both the general and matched sample (p < 0.05 for each group comparison). The negative association of total cholesterol and mortality persisted when cholesterol was treated as a continuous variable (HR 0.83, 95%CI 0.77–0.90, p < 0.001 for matched patients), but it was less pronounced in statin users than in non-users (F-test p < 0.001).\ud \ud Conclusions:\ud \ud Statins attenuate but do not eliminate the reverse epidemiological association between increasing total serum cholesterol and improved survival in patients with non-ischemic CHF.

Angiotensin-converting enzyme inhibitors (ACEIs) are recommended as first-line therapy in patients with heart failure with reduced ejection fraction (HFrEF). The comparative effectiveness of different ACEIs is not known.A total of 4723 outpatients with stable HFrEF prescribed enalapril, lisinopril, or ramipril were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and their respective propensity scores for ACEI treatment. During a follow-up of 21 939 patient-years, 360 (49.5%), 337 (52.4%), and 1119 (33.4%) patients died among those prescribed enalapril, lisinopril, and ramipril, respectively. In univariable analysis of the general sample, enalapril and lisinopril were both associated with higher mortality when compared with ramipril treatment [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.30-1.65, P 0.001 and HR 1.38, 95% CI 1.22-1.56, P 0.001, respectively). Patients prescribed enalapril or lisinopril had similar mortality (HR 1.06, 95% CI 0.92-1.24, P = 0.41). However, there was no significant association between ACEI choice and all-cause mortality in any of the matched samples (HR 1.07, 95% CI 0.91-1.25, P = 0.40; HR 1.12, 95% CI 0.96-1.32, P = 0.16; and HR 1.10, 95% CI 0.93-1.31, P = 0.25 for enalapril vs. ramipril, lisinopril vs. ramipril, and enalapril vs. lisinopril, respectively). Results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, New York Class Association functional class, cause of HFrEF, rhythm, and systolic blood pressure.Our results suggest that enalapril, lisinopril, and ramipril are equally effective in the treatment of patients with HFrEF when given at equivalent doses.

To investigate differences in prognosis after myocardial infarction (MI) in patients classified according to the old and new definitions of MI. Patients not fulfilling the old definitions were classified as having a micro MI.Data on 1216 consecutive patients with a diagnosis of first MI (38.3% women) and who were discharged from or died in one hospital in the 5-year period from 2001 were included in the study. Surviving patients were followed for a mean of 8.2 years. Risk factors and death after MI were analysed according to MI classification.Of the patients, 20.1% were classified as having a micro MI. During follow-up, 47.2% of all the patients died. Patients with micro MI were older and fewer were current smokers than patients with other MI. In multivariate Cox regression analysis for the total risk of mortality, age, diabetes mellitus, a positive smoking history, history of stroke and living alone were significantly related to long-term prognosis, and there was no difference in long-term survival between the two types of MI (p 0.50).After adjustment for confounders, patients with micro MI had no significant difference in long-term survival compared with those with other MI.

Objectives The aim of this study was to evaluate the prognostic impact of anemia in outpatients with chronic heart failure attending specialized heart failure clinics and specifically to investigate its prognostic utility in patients with severe renal dysfunction or advanced heart failure. Background Anemia is an independent prognostic marker in patients with heart failure. The effect of anemia on mortality decreases with increasing creatinine levels. Methods Multivariate Cox regression analyses were used to investigate the prognostic effect of anemia in 4,144 patients with heart failure from 21 outpatient heart failure clinics in Norway. Severe renal failure was defined as estimated glomerular filtration rate ≤45 ml/min/1.73 m 2 and advanced heart failure as New York Heart Association functional classes IIIb and IV. Results Baseline anemia was present in 24% and was a strong predictor of all-cause mortality (adjusted hazard ratio [HR]: 1.30, 95% CI: 1.09 to 1.56, p = 0.004). Baseline anemia did not predict mortality in the 752 patients with severe renal dysfunction (adjusted HR: 1.08, 95 % CI: 0.77 to 1.51, p = 0.662) and the 528 patients with advanced heart failure (adjusted HR: 0.87, 95% CI: 0.56 to 1.34, p = 0.542). In the 1,743 patients who attended subsequent visits, sustained anemia independently predicted worse prognosis (adjusted HR: 1.47, 95% CI: 1.10 to 1.94, p = 0.008), whereas transient and new-onset anemia did not. Conclusions According to our study, baseline anemia was not an independent predictor of all-cause mortality in outpatients with heart failure and accompanied severe renal dysfunction or advanced heart disease. Sustained anemia after optimizing heart failure treatment might imply worse prognosis independently of renal function and New York Heart Association functional class.

Hospitalization rates, morbidity and mortality are undesirably high in heart failure (HF) patients. An organized system of HF specialist outpatient care has been recommended, but the best way to implement such programmes is not clearly established.To evaluate HF patient characteristics, management and outcome in outpatient HF clinics.Data from HF patients at 24 hospital outpatient clinics were entered in a common database allowing each centre to monitor its own practice against the rest.A total of 3632 patients were included. At the last registered visit, ACE inhibitors or angiotensin receptor blockers were prescribed for 87%; beta blockers, 83%; spironolactone, 33% and loop diuretics 87% of the patients. The number of hospital admissions and days stayed in hospital for cardiovascular reasons were significantly reduced (p0.001). Mortality was high, 11.5 and 22% after one and two years, respectively.The use of evidence-based medication increased over time in HF clinics with the ability of the individual clinics to compare their treatment to other sites. Thus, establishment of specialized HF clinics managed in a registry network might improve the quality of care.

We have shown previously that smoking causes a first myocardial infarction (MI) to occur significantly more prematurely in women than in men. The aim of the study was to investigate mortality after MI with special emphasis on the impact of smoking and gender. The study included 2,281 consecutive patients (36.8% women) who died or were discharged from a central hospital with a diagnosis of MI from 1998 to 2005; the median follow-up of survivors was 7 years. Death after MI was adjusted for confounders. Mean age for women was 5.8 years older than for men (76.0 vs. 70.2 years) and women were less likely to have been smokers. In-hospital mortality for the first MI was 8.9% for men and 13.3% for women, and total mortality rates for all indexed MI after 7 years were 47% for men and 61% for women. Using Cox regression analysis, with all indexed MIs included, the after-discharge mortality for women was significantly lower than for men (hazard ratio 0.82; 95% confidence interval 0.70-0.96; P = 0.015). Compared with non-smokers, patients who were smokers on admission had significantly increased seven-year mortality after discharge (hazard ratio 1.30; 95% confidence interval 1.03-1.63; P = 0.002). In conclusion, current smoking at the time of the indexed MI was associated with increased mortality after 7 years follow-up. The smoking effect was independent of gender. Female gender was associated with a moderately lower risk of death during the same follow-up period.

Impaired renal function confers an adverse prognosis in patients with heart failure (HF). The aims of the present study were to identify factors associated with and predictive of impaired renal function and to assess the relationship between estimated glomerular filtration rate (eGFR) and all-cause mortality in outpatients with HF.Baseline data on 3605 patients (median age 73 years, 70.1% men) from 24 outpatient HF clinics in Norway were analyzed. Median follow-up time was 9 months. Renal dysfunction (eGFR60 mL/min) was present in 44.9%. The population was randomized into equal-sized model-building and validation samples to enhance model stability. eGFR was an independent predictor of all-cause mortality (HR 0.94 per 5 mL/min increase, P = .001). Use of spironolactone (P = .002), higher blood pressure (P.001), and lower hemoglobin levels (P = .002) were predictors of impaired renal function. Increasing doses of loop diuretics were strongly associated with eGFR at baseline (P.001), but only tended to predict worsening renal function during follow-up (P = .08).Clinically significant reduction in renal function was prevalent in outpatients with HF, and was a strong predictor of all-cause mortality. Use of loop diuretics and spironolactone should be carefully evaluated as these agents may adversely affect renal function.

It has been debated whether smoking increases the risk of heart disease relatively more in women than in men. It is not known whether there are sex differences with regard to how many years prematurely smoking causes acute myocardial infarction (AMI) to occur. We aimed to determine how smoking affects the age of onset of first myocardial infarction in both the sexes.Clinical data were consecutively entered into a database and were analysed with a multivariate regression technique.In the years 1998-2005, data on 1784 consecutive patients (38.3% women) who were discharged from or died in a district general hospital with a diagnosis of first myocardial infarction were included in the study. Age at first AMI was analysed.Unadjusted mean ages were 76.2 years for women and 69.8 years for men, a difference of 6.4 years (P0.001). Mean age within the various groups was: women nonsmokers 80.7 years, women smokers 66.2 years, difference 14.4 years (P0.001); men nonsmokers 72.2 years, men smokers 63.9 years, difference 8.3 years (P0.001). After adjustment for risk factors (hypertension, cholesterol levels, diabetes) and patient characteristics (history of angina, history of stroke) 13.7 years of the age difference in women were attributed to smoking; the corresponding figure in men was 6.2 years (P0.001).First AMI occurred significantly more prematurely in women than in men smokers, implying that twice as many years were lost by women as by men smokers.

The increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been recognized for many years. However, although the characteristics of CVD and its burden resemble those in diabetes, the focus on cardiovascular (CV) prevention in RA has lagged behind, both in the clinical and research settings. Similar to diabetes, the clinical picture of CVD in RA may be atypical, even asymptomatic. Therefore, a proactive screening for subclinical CVD in RA is warranted. Because of the lack of clinical trials, the ideal CVD prevention (CVP) in RA has not yet been defined. In this article, we focus on challenges and controversies in the CVP in RA (such as thresholds for statin therapy), and propose recommendations based on the current evidence. Due to the significant contribution of non-traditional, RA-related CV risk factors, the CV risk calculators developed for the general population underestimate the true risk in RA. Thus, there is an enormous need to develop adequate CV risk stratification tools and to identify the optimal CVP strategies in RA. While awaiting results from randomized controlled trials in RA, clinicians are largely dependent on the use of common sense, and extrapolation of data from studies on other patient populations. The CVP in RA should be based on an individualized evaluation of a broad spectrum of risk factors, and include: 1) reduction of inflammation, preferably with drugs decreasing CV risk, 2) management of factors associated with increased CV risk (e.g., smoking, hypertension, hyperglycemia, dyslipidemia, kidney disease, depression, periodontitis, hypothyroidism, vitamin D deficiency and sleep apnea), and promotion of healthy life style (smoking cessation, healthy diet, adjusted physical activity, stress management, weight control), 3) aspirin and influenza and pneumococcus vaccines according to current guidelines, and 4) limiting use of drugs that increase CV risk. Rheumatologists should take responsibility for the education of health care providers and RA patients regarding CVP in RA. It is immensely important to incorporate CV outcomes in testing of anti-rheumatic drugs.

Aims To assess the adherence to heart failure (HF) guidelines for angiotensin-converting enzyme-I (ACE-I), angiotensin II receptor blockers (ARB), and β-blockers and the possible association of ACE-I or ARB, β-blockers, and statins with survival in the large contemporary Norwegian Heart Failure Registry . Methods and results The study included 5761 outpatients who were diagnosed with HF of any aetiology (mean left ventricular ejection fraction 32% ± 11%) from January 2000 to January 2010 and followed up until death or February 2010. Adherence to treatment according to the guidelines was high. Cox regression analysis to identify risk factors for all-cause mortality, after adjustment for many factors, showed that ACE-I ≥ 50% of target dose, use of beta-blockers, and statins were significantly related to improved survival ( P = 0.003, P < 0.001, and P < 0.001, respectively). Propensity scoring showed the same benefit for these variables. Conclusions Both multivariable and propensity scoring analyses showed survival benefits with β-blockers, statins, and adequate doses of ACE-I in this contemporary HF cohort. This study stresses the importance of guidelines adherence, even in the context of high levels of adherence to guidelines. Moreover, respecting the recommended target doses of ACE-I appears to have a crucial role in survival improvement and, in the multivariate Cox regression analysis, ARB treatment was not significantly associated with a lower all-cause mortality. [10.1093/ehjcvp/pvu015][1] [1]: /lookup/doi/10.1093/ehjcvp/pvu015

To test the hypothesis that a statin could reduce the recurrence rate of atrial fibrillation after electrical cardioversion (EC), we performed an open, controlled multicenter study. Patients (n = 114) who had atrial fibrillation >48 hours and who were scheduled for EC were randomized to receive 40 mg of pravastatin once daily for 3 weeks before and 6 weeks after EC or no drug in addition to standard therapy. Pravastatin did not reduce the recurrence rate of atrial fibrillation after EC.

The aim was to investigate possible gender differences in the years of life lost after acute myocardial infarction (MI) and to explore how smoking affects life expectancy in the two genders.In the years 1998-2005, 2281 patients (36.8% women) who were discharged from or died in hospital following a diagnosis of MI were included. Survivors were followed for a mean of 8 years. The age of death for each patient was subtracted from the average projected age of death for individuals in the general population with a similar age to the patient at the time of their MI. The effects of gender, smoking, and other risk factors on the years of life lost were analysed.During follow-up, 55% of the patients died. Non-smokers, ex-smokers and current smokers lost 5.4, 6.4 and 10.3 years of life, respectively. Structural equation modeling showed that currently smoking men lost 4.2 more years more than did non-smoking men (P0.001), and this was mediated through more prematurely occurring MIs. Female current smokers lost 1.9 years more than male current smokers and female ex-smokers lost 1.8 years more than male ex-smokers (both P0.001).MI caused a substantial number of years of life lost, with a heavier loss in current smokers than in ex-smokers and non-smokers. The effect was predominantly related to the patient's age at the event. More years of life were lost among smoking women than among smoking men, indicating that smoking is most detrimental for the female gender.

The aim of this study was to evaluate the prognostic impact of anemia in outpatients with chronic heart failure attending specialized heart failure clinics and specifically to investigate its prognostic utility in patients with severe renal dysfunction or advanced heart failure.Anemia is an independent prognostic marker in patients with heart failure. The effect of anemia on mortality decreases with increasing creatinine levels.Multivariate Cox regression analyses were used to investigate the prognostic effect of anemia in 4,144 patients with heart failure from 21 outpatient heart failure clinics in Norway. Severe renal failure was defined as estimated glomerular filtration rate ≤45 ml/min/1.73 m(2) and advanced heart failure as New York Heart Association functional classes IIIb and IV.Baseline anemia was present in 24% and was a strong predictor of all-cause mortality (adjusted hazard ratio [HR]: 1.30, 95% CI: 1.09 to 1.56, p = 0.004). Baseline anemia did not predict mortality in the 752 patients with severe renal dysfunction (adjusted HR: 1.08, 95 % CI: 0.77 to 1.51, p = 0.662) and the 528 patients with advanced heart failure (adjusted HR: 0.87, 95% CI: 0.56 to 1.34, p = 0.542). In the 1,743 patients who attended subsequent visits, sustained anemia independently predicted worse prognosis (adjusted HR: 1.47, 95% CI: 1.10 to 1.94, p = 0.008), whereas transient and new-onset anemia did not.According to our study, baseline anemia was not an independent predictor of all-cause mortality in outpatients with heart failure and accompanied severe renal dysfunction or advanced heart disease. Sustained anemia after optimizing heart failure treatment might imply worse prognosis independently of renal function and New York Heart Association functional class.

Background: Several studies have shown that atrial fibrillation (AF) is associated with increased risk of death in heart failure (HF) patients. However, it is not clear whether this increased risk is independent of other risk factors. Hypothesis: We hypothesized that AF would be an independent risk factor for death in a large cohort of HF patients. Methods: Patients referred to Norwegian HF outpatient clinics were enrolled between October 2000 and February 2008. Patients with heart rhythm other than AF or sinus rhythm were excluded. Mortality data were obtained from the National Statistics Bureau, Statistics Norway with the last update February 2008. Results: There were 4048 patients included in the analysis, with a median follow-up of 28 months. Adherence to guidelines regarding medical treatment was high. In univariate analysis, AF patients (n = 1391) had a higher risk of death than patients in sinus rhythm (n = 2657) (hazard ratio [HR] 1.181; 95% confidence interval (CI), 1.044–1.336; P = 0.008). However, after adjusting for confounding factors (age, New York Heart Association class, coronary artery disease as the main cause of HF, use of any loop diuretic, hemoglobin level, and serum creatinine), AF was no longer associated with increased risk of death (HR 1.037; 95% CI, 0.901–1.193; P = 0.619). Conclusions: In this cohort of heart failure patients receiving optimal medical treatment at specialized HF clinics, AF was not associated with increased risk of death after adjusting for confounding factors. © 2011 Wiley Periodicals, Inc. AstraZeneca Norway provided secretarial assistance in maintaining the Norwegian heart failure registry by financing an independent IT consultant. The authors have received research grants, consultancy fees, and/or honoraria for lectures from several pharmaceutical companies. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Aims To evaluate the quality of life in heart failure (HF) outpatients attending multidisciplinary disease management programmes at HF clinics in Norwegian hospitals. Methods and results Data from HF patients at 24 hospital outpatient clinics were entered in a common database; The Norwegian Heart Failure Registry. Quality of life assessment was done using Minnesota Living with Heart Failure Questionnaire (MLHF). The quality of life assessment was optional at each hospital and was done both at initial evaluation and after 6 months of stable follow-up. A total of 3632 patients were included in the registry and 1778 patients had at least one assessment of quality of life. The mean MLHF score improved significantly from 2.1 at the initial evaluation to 1.4 six months after leaving the clinic (P < 0.001). There was a significant difference in MLHF score between hospitals and baseline MLHF score was significantly associated with NYHA functional class, hospitalizations 6 months before entering the registry, and brain natriuretic peptide; and inversely related to age and systolic blood pressure. Minnesota Living with Heart Failure score was an independent predictor of mortality in this population. Conclusion Quality of life assessed with MLHF improved after follow-up at outpatient HF clinics. Minnesota Living with Heart Failure score was significantly related to functional status, laboratory and demographic variables, and was an important predictor of prognosis.

Lainchbury et al. ([1][1]) compared the effect of treatment guided by N-terminal pro-B-type natriuretic peptide with intensive clinical management and usual care among 364 patients with chronic heart failure ([1][1]). They concluded that intensive management of chronic heart failure, when compared