Downloaded from http://heart.bmj.com/ on July 5, 2015 - Published by group.bmj.com
Heart failure and cardiomyopathies
ORIGINAL ARTICLE
Risk factors, treatment and prognosis in men and women with heart failure with and without diabetes Isabelle Johansson,1 Ulf Dahlström,2 Magnus Edner,1 Per Näsman,3 Lars Rydén,1 Anna Norhammar1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2014-307131). 1
Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm 2 Department of Cardiology and Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden 3 Center for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden Correspondence to Dr Isabelle Johansson, Cardiology Unit, Department of Medicine, N3:06, Karolinska University Hospital Solna, Stockholm SE-171 76, Sweden; [email protected] Received 5 November 2014 Revised 28 April 2015 Accepted 29 April 2015 Published Online First 1 June 2015
ABSTRACT Objective To test the hypothesis that risk factor pattern, treatment and prognosis differ between men and women with heart failure (HF) with and without diabetes in the Swedish Heart Failure Registry. Methods Patients with (n=8809) and without (n=27 465) type 2 diabetes (T2DM) included in the Swedish Heart Failure Registry (2003–2011) were followed for mortality during a median follow-up of 1.9 years (range 0–8.7 years). All-cause mortality, differences in background and HF characteristics were analysed in women and men with and without T2DM and with a special regard to different age groups. Results Of 36 274 patients, 24% had T2DM and 39% were women. In patients with T2DM, women were older than men (78 years vs 73 years), more frequently had hypertension, renal dysfunction and preserved ventricular function. Regardless of T2DM status, women with reduced ventricular function, compared with their male counterparts, were less frequently offered, for example, ACE inhibitors/angiotensin receptor II blockers (ARB). Absolute mortality was 48% in women with T2DM, 40% in women without; corresponding male mortality rates were 43% and 35%, respectively. Kaplan-Meier curves revealed shorter longevity in women with T2DM but female sex did not remain a significant mortality predictor following adjustment (OR 95% CI 0.90; 0.79 to 1.03). In those without T2DM, women compared with men lived longer; this pattern remained after adjustment (OR 0.72; 0.66 to 0.78). T2DM was a stronger predictor of mortality in women (OR 1.72; 1.53 to 1.94) than in men (OR 1.47; 1.34 to 1.61). Conclusions T2DM is a strong mortality predictor in men and women with HF, somewhat stronger in women. The shorter survival time in women with T2DM and HF related to comorbidities rather than sex per se. Evidencebased management was less prevalent in women. Mechanisms behind these findings remain incompletely understood and need further attention.
first described in 1961 by Sievers et al,7 and in 1974, Kannel et al8 reported increased risk for future HF in women with diabetes based on the Framingham cohort. Since then the management of HF and diabetes has developed. Based on clinical trials it is obvious that, although still impaired, the longevity of patients with HF, including those with diabetes, has improved.9 10 However, clinical trials do not mirror everyday clinical practice recruiting proportionately healthier individuals and excluding those at high age causing a lower inclusion of patients with diabetes and of female sex making available information on sex differences in patients with HF contradictory. We hypothesised that sex influences the risk factor pattern, prescribed treatment and the vital prognosis in patients with HF to the disadvantage of women with diabetes and explored this through analyses of a contemporary, large and unselected HF population.
MATERIAL AND METHODS Source of data The nationwide Swedish Heart Failure Registry (S-HFR) has been presented in detail.11 Registry information, the registration forms and annual reports are available at http://www.rikssvikt.se. Participating centres located at 65 hospitals and 113 outpatient clinics report to the registry, which in 2011 comprised information on 47 000 patients. The main inclusion criterion is a physician-judged diagnosis of HF and 76 variables are recorded via an internet-based case report form at hospital discharge or outpatient visits. Data are entered into a database managed by the Uppsala Clinical Research Center (Uppsala, Sweden) and run against the Swedish Population Registry using the unique tendigit personal identification number of each Swedish citizen.
Study population INTRODUCTION
To cite: Johansson I, Dahlström U, Edner M, et al. Heart 2015;101: 1139–1148.
In general women are protected from premature cardiovascular disease, but the presence of diabetes attenuates this characteristic.1 2 Thus women with diabetes suffer their first myocardial infarction at an age approaching that in men.3 Moreover, women with diabetes have an increased postinfarction mortality, which has been related to a high prevalence of heart failure (HF),4 5 in combination with an underuse of evidence-based management.6 The high prevalence of and poor prognosis after myocardial infarction in women with diabetes were
The present study addresses patients registered at hospital-based (68%) and specialised outpatient (32%) HF clinics during January 2003–September 2011 (n=36 595). Sex information was obtained from the Swedish personal identification number. Following exclusion of patients with incomplete information on sex (n=53) or glycaemic state (n=123) and with type 1 diabetes (n=198), the population consisted of 36 274 individuals, of whom 14 297 (39%) were women and 21 977 (61%) men; 8809 (24%; 37% women) had type 2 diabetes (T2DM) (figure 1). The main outcome variable was all-cause mortality, obtained by
Johansson I, et al. Heart 2015;101:1139–1148. doi:10.1136/heartjnl-2014-307131
1139
Downloaded from http://heart.bmj.com/ on July 5, 2015 - Published by group.bmj.com
Heart failure and cardiomyopathies merging the S-HFR database with the Swedish Population Registry. The last day of follow-up was September 13, 2011.
Definitions A description of definitions used in the S-HFR is reported in online supplementary appendix A. Heart failure: diagnosed by the attending physician based on guideline recommendations at the time of inclusion. New York Heart Association (NYHA) classes I to IV were used to express HF severity. Presence of ischaemic, valvular or hypertensive heart disease, as well as idiopathic dilated cardiomyopathy, was recorded. Ischaemic heart disease (IHD): was grouped as verified/not verified by coronary angiography, according to the physician-based classification. Type 2 diabetes: defined as a history of this diagnosis combined with treatment (lifestyle advice, oral glucose-lowering drugs and/or insulin). Revascularisation: implied a history of coronary artery bypass surgery and/or a percutaneous coronary intervention. Hypertension: based on case history or ongoing blood pressure-lowering therapy. LVEF: the most recent estimated LVEF (optional method) grouped into four different classes: ≥50%, 40–50%, 30–39% and 80 years) were estimated using the logrank test, while survival curves were produced using Kaplan-Meier analyses. Due to low numbers at risk in the last years of follow-up, the Kaplan-Meier curves were truncated at 6 years. A formal test for interaction between mortality, sex and T2DM did not reveal any overall interaction ( p=0.74). Still sex aspects were further evaluated for the three defined age groups and additional comparisons performed between the following three groups: (1) men and women with T2DM; (2) women ±T2DM; (3) men±T2DM (figure 1). In the total population, multivariate logistic regression models were used to evaluate the importance of sex and T2DM as predictors of all-cause mortality. Variables adjusted for had fewer than 5% missing data reported and a univariate p value of 80 Weight (kg; mean (SD)) Smoking habits (%; never/former/current) Duration of heart failure (%; below/above 6 months) NYHA I II III IV Heart rate (bpm; mean (SD)) Blood pressure (mm Hg; mean (SD)) Systolic Diastolic Pulse pressure (mm Hg; mean (SD)) Mean arterial pressure (mm Hg; mean (SD)) Previous or present disease Ischaemic heart disease Verified by coronary angiography Hypertension Atrial fibrillation Pulmonary disease Valvular heart disease Idiopathic dilated cardiomyopathy Previous interventions Revascularisation (CABG/PCI) Valvular surgery Investigations of ventricular function Echocardiography LVEF ≥50% LVEF 40–49% LVEF 30–39% LVEF
Heart failure and cardiomyopathies
ORIGINAL ARTICLE
Risk factors, treatment and prognosis in men and women with heart failure with and without diabetes Isabelle Johansson,1 Ulf Dahlström,2 Magnus Edner,1 Per Näsman,3 Lars Rydén,1 Anna Norhammar1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2014-307131). 1
Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm 2 Department of Cardiology and Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden 3 Center for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden Correspondence to Dr Isabelle Johansson, Cardiology Unit, Department of Medicine, N3:06, Karolinska University Hospital Solna, Stockholm SE-171 76, Sweden; [email protected] Received 5 November 2014 Revised 28 April 2015 Accepted 29 April 2015 Published Online First 1 June 2015
ABSTRACT Objective To test the hypothesis that risk factor pattern, treatment and prognosis differ between men and women with heart failure (HF) with and without diabetes in the Swedish Heart Failure Registry. Methods Patients with (n=8809) and without (n=27 465) type 2 diabetes (T2DM) included in the Swedish Heart Failure Registry (2003–2011) were followed for mortality during a median follow-up of 1.9 years (range 0–8.7 years). All-cause mortality, differences in background and HF characteristics were analysed in women and men with and without T2DM and with a special regard to different age groups. Results Of 36 274 patients, 24% had T2DM and 39% were women. In patients with T2DM, women were older than men (78 years vs 73 years), more frequently had hypertension, renal dysfunction and preserved ventricular function. Regardless of T2DM status, women with reduced ventricular function, compared with their male counterparts, were less frequently offered, for example, ACE inhibitors/angiotensin receptor II blockers (ARB). Absolute mortality was 48% in women with T2DM, 40% in women without; corresponding male mortality rates were 43% and 35%, respectively. Kaplan-Meier curves revealed shorter longevity in women with T2DM but female sex did not remain a significant mortality predictor following adjustment (OR 95% CI 0.90; 0.79 to 1.03). In those without T2DM, women compared with men lived longer; this pattern remained after adjustment (OR 0.72; 0.66 to 0.78). T2DM was a stronger predictor of mortality in women (OR 1.72; 1.53 to 1.94) than in men (OR 1.47; 1.34 to 1.61). Conclusions T2DM is a strong mortality predictor in men and women with HF, somewhat stronger in women. The shorter survival time in women with T2DM and HF related to comorbidities rather than sex per se. Evidencebased management was less prevalent in women. Mechanisms behind these findings remain incompletely understood and need further attention.
first described in 1961 by Sievers et al,7 and in 1974, Kannel et al8 reported increased risk for future HF in women with diabetes based on the Framingham cohort. Since then the management of HF and diabetes has developed. Based on clinical trials it is obvious that, although still impaired, the longevity of patients with HF, including those with diabetes, has improved.9 10 However, clinical trials do not mirror everyday clinical practice recruiting proportionately healthier individuals and excluding those at high age causing a lower inclusion of patients with diabetes and of female sex making available information on sex differences in patients with HF contradictory. We hypothesised that sex influences the risk factor pattern, prescribed treatment and the vital prognosis in patients with HF to the disadvantage of women with diabetes and explored this through analyses of a contemporary, large and unselected HF population.
MATERIAL AND METHODS Source of data The nationwide Swedish Heart Failure Registry (S-HFR) has been presented in detail.11 Registry information, the registration forms and annual reports are available at http://www.rikssvikt.se. Participating centres located at 65 hospitals and 113 outpatient clinics report to the registry, which in 2011 comprised information on 47 000 patients. The main inclusion criterion is a physician-judged diagnosis of HF and 76 variables are recorded via an internet-based case report form at hospital discharge or outpatient visits. Data are entered into a database managed by the Uppsala Clinical Research Center (Uppsala, Sweden) and run against the Swedish Population Registry using the unique tendigit personal identification number of each Swedish citizen.
Study population INTRODUCTION
To cite: Johansson I, Dahlström U, Edner M, et al. Heart 2015;101: 1139–1148.
In general women are protected from premature cardiovascular disease, but the presence of diabetes attenuates this characteristic.1 2 Thus women with diabetes suffer their first myocardial infarction at an age approaching that in men.3 Moreover, women with diabetes have an increased postinfarction mortality, which has been related to a high prevalence of heart failure (HF),4 5 in combination with an underuse of evidence-based management.6 The high prevalence of and poor prognosis after myocardial infarction in women with diabetes were
The present study addresses patients registered at hospital-based (68%) and specialised outpatient (32%) HF clinics during January 2003–September 2011 (n=36 595). Sex information was obtained from the Swedish personal identification number. Following exclusion of patients with incomplete information on sex (n=53) or glycaemic state (n=123) and with type 1 diabetes (n=198), the population consisted of 36 274 individuals, of whom 14 297 (39%) were women and 21 977 (61%) men; 8809 (24%; 37% women) had type 2 diabetes (T2DM) (figure 1). The main outcome variable was all-cause mortality, obtained by
Johansson I, et al. Heart 2015;101:1139–1148. doi:10.1136/heartjnl-2014-307131
1139
Downloaded from http://heart.bmj.com/ on July 5, 2015 - Published by group.bmj.com
Heart failure and cardiomyopathies merging the S-HFR database with the Swedish Population Registry. The last day of follow-up was September 13, 2011.
Definitions A description of definitions used in the S-HFR is reported in online supplementary appendix A. Heart failure: diagnosed by the attending physician based on guideline recommendations at the time of inclusion. New York Heart Association (NYHA) classes I to IV were used to express HF severity. Presence of ischaemic, valvular or hypertensive heart disease, as well as idiopathic dilated cardiomyopathy, was recorded. Ischaemic heart disease (IHD): was grouped as verified/not verified by coronary angiography, according to the physician-based classification. Type 2 diabetes: defined as a history of this diagnosis combined with treatment (lifestyle advice, oral glucose-lowering drugs and/or insulin). Revascularisation: implied a history of coronary artery bypass surgery and/or a percutaneous coronary intervention. Hypertension: based on case history or ongoing blood pressure-lowering therapy. LVEF: the most recent estimated LVEF (optional method) grouped into four different classes: ≥50%, 40–50%, 30–39% and 80 years) were estimated using the logrank test, while survival curves were produced using Kaplan-Meier analyses. Due to low numbers at risk in the last years of follow-up, the Kaplan-Meier curves were truncated at 6 years. A formal test for interaction between mortality, sex and T2DM did not reveal any overall interaction ( p=0.74). Still sex aspects were further evaluated for the three defined age groups and additional comparisons performed between the following three groups: (1) men and women with T2DM; (2) women ±T2DM; (3) men±T2DM (figure 1). In the total population, multivariate logistic regression models were used to evaluate the importance of sex and T2DM as predictors of all-cause mortality. Variables adjusted for had fewer than 5% missing data reported and a univariate p value of 80 Weight (kg; mean (SD)) Smoking habits (%; never/former/current) Duration of heart failure (%; below/above 6 months) NYHA I II III IV Heart rate (bpm; mean (SD)) Blood pressure (mm Hg; mean (SD)) Systolic Diastolic Pulse pressure (mm Hg; mean (SD)) Mean arterial pressure (mm Hg; mean (SD)) Previous or present disease Ischaemic heart disease Verified by coronary angiography Hypertension Atrial fibrillation Pulmonary disease Valvular heart disease Idiopathic dilated cardiomyopathy Previous interventions Revascularisation (CABG/PCI) Valvular surgery Investigations of ventricular function Echocardiography LVEF ≥50% LVEF 40–49% LVEF 30–39% LVEF
