Morten Grundtvig

Prevention of cardiovascular disease in rheumatoid arthritis

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.

Renal Function in Outpatients With Chronic Heart Failure

BACKGROUND 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. METHODS AND RESULTS 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 (eGFR < 60 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). CONCLUSIONS 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.

Sex-based differences in premature first myocardial infarction caused by smoking: twice as many years lost by women as by men

Background 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. Design Clinical data were consecutively entered into a database and were analysed with a multivariate regression technique. Methods 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. Results Unadjusted mean ages were 76.2 years for women and 69.8 years for men, a difference of 6.4 years (P < 0.001). Mean age within the various groups was: women nonsmokers 80.7 years, women smokers 66.2 years, difference 14.4 years (P < 0.001); men nonsmokers 72.2 years, men smokers 63.9 years, difference 8.3 years (P < 0.001). 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 (P < 0.001). Conclusion 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. Eur J Cardiovasc Prev Rehabil 16:174-179

Baseline anemia is not a predictor of all-cause mortality in outpatients with advanced heart failure or severe renal dysfunction. Results from the Norwegian Heart Failure Registry.

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.

Clinical ResearchHeart FailureBaseline Anemia Is Not a Predictor of All-Cause Mortality in Outpatients With Advanced Heart Failure or Severe Renal Dysfunction: Results From the Norwegian Heart Failure Registry

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.

Characteristics, Implementation of Evidence-Based Management and Outcome in Patients with Chronic Heart Failure Results from the Norwegian Heart Failure Registry

Background: 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. Aim: To evaluate HF patient characteristics, management and outcome in outpatient HF clinics. Methods: 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. Results: 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 (p < 0.001). Mortality was high, 11.5 and 22% after one and two years, respectively. Conclusions: 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.

ESC guidelines adherence is associated with improved survival in patients from the Norwegian Heart Failure Registry

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.

No Impact of Atrial Fibrillation on Mortality Risk in Optimally Treated Heart Failure Patients

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.

Improved quality of life in Norwegian heart failure patients after follow-up in outpatient heart failure clinics: results from the Norwegian heart failure registry

To evaluate the quality of life in heart failure (HF) outpatients attending multidisciplinary disease management programmes at HF clinics in Norwegian hospitals.

Reduced life expectancy after an incident hospital diagnosis of acute myocardial infarction--effects of smoking in women and men.

BACKGROUND 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. METHODS 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. RESULTS 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 (P<0.001), 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 P<0.001). CONCLUSIONS 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 patients 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.