Heart failure in patients with congenital heart disease after a cancer diagnosis.

AIMS: Individuals with congenital heart disease (CHD) are at an increased risk for cancer. As cancer survival rates improve, the prevalence of late side effects, such as heart failure (HF), is becoming more evident. This study aims to evaluate the risk of developing HF following a cancer diagnosis in patients with CHD, compared with those without CHD and with CHD patients who do not have cancer. METHODS: CHD patients (n = 69 799) and randomly selected non-CHD controls (n = 650 406), born in Sweden between 1952 and 2017, were identified from the Swedish National Health Registers and Total Population Register (excluding those with syndromes and transplant recipients). CHD patients who developed cancer (n = 1309) were propensity score-matched with non-CHD patients who developed cancer (n = 9425), resulting in a cohort of 1232 CHD patients with cancer and 2602 non-CHD controls with cancer (after exclusion of individuals with HF prior to cancer diagnosis). In a separate analysis, CHD patients with cancer were propensity score-matched with CHD patients without cancer (n = 68 490). A total of 1233 CHD patients with cancer and 2257 CHD patients without cancer were included in the study. RESULTS: Among CHD patients with cancer, 73 (5.9%) developed HF during a mean follow-up time of 8.5 ± 8.7. Comparatively, in the propensity-matched control population, 29 (1.1%) non-CHD cancer patients (mean follow-up time of 7.3 ± 7.5) and 101 (4.5%) CHD patients without cancer (mean follow-up time of 9.9 ± 9.2) developed HF. CHD patients exhibited a significantly higher risk of HF post-cancer diagnosis compared with the non-CHD control group [hazard ratio (HR) 4.39, 95% confidence interval (CI) 2.83-6.81], after adjusting for age at cancer diagnosis and comorbidities. In the analysis between CHD patients with cancer and those without cancer, the results indicated a significantly higher risk of developing HF in CHD patients with cancer (HR 1.53, 95% CI 1.13-2.07). CONCLUSIONS: CHD patients face a more than four-fold increased risk of developing HF after a cancer diagnosis compared with cancer patients without CHD. Among CHD patients, the risk of HF is only modestly higher for those with cancer than for those without cancer. This suggests that the increased HF risk in CHD patients with cancer, relative to non-CHD cancer patients, may be more attributable to CHD itself than to cancer treatment-related side effects.

Outcomes after cancer diagnosis in children and adult patients with congenital heart disease in Sweden: a registry-based cohort study.

OBJECTIVE: Patients with congenital heart disease (CHD) have an increased cancer risk. The aim of this study was to determine cancer-related mortality in CHD patients compared with non-CHD controls, compare ages at cancer diagnosis and death, and explore the most fatal cancer diagnoses. DESIGN: Registry-based cohort study. SETTING AND PARTICIPANTS: CHD patients born between 1970 and 2017 were identified using Swedish Health Registers. Each was matched by birth year and sex with 10 non-CHD controls. Included were those born in Sweden with a cancer diagnosis. RESULTS: Cancer developed in 758 out of 67814 CHD patients (1.1%), with 139 deaths (18.3%)-of which 41 deaths occurred in patients with genetic syndromes. Cancer was the cause of death in 71.9% of cases. Across all CHD patients, cancer accounted for 1.8% of deaths. Excluding patients with genetic syndromes and transplant recipients, mortality risk between CHD patients with cancer and controls showed no significant difference (adjusted HR 1.17; 95% CI 0.93 to 1.49). CHD patients had a lower median age at cancer diagnosis-13.0 years (IQR 2.9-30.0) in CHD versus 24.6 years (IQR 8.6-35.1) in controls. Median age at death was 15.1 years (IQR 3.6-30.7) in CHD patients versus 18.5 years (IQR 6.1-32.7) in controls. The top three fatal cancer diagnoses were ill-defined, secondary and unspecified, eye and central nervous system tumours and haematological malignancies. CONCLUSIONS: Cancer-related deaths constituted 1.8% of all mortalities across all CHD patients. Among CHD patients with cancer, 18.3% died, with cancer being the cause in 71.9% of cases. Although CHD patients have an increased cancer risk, their mortality risk post-diagnosis does not significantly differ from non-CHD patients after adjustements and exclusion of patients with genetic syndromes and transplant recipients. However, CHD patients with genetic syndromes and concurrent cancer appear to be a vulnerable group.

Corrigendum to "Risk of cancer in young and older patients with congenital heart disease and the excess risk of cancer by syndromes, organ transplantation and cardiac surgery: Swedish health registry study (1930-2017)" [The Lancet Regional Health-Europe 18 (2022) 100407].

[This corrects the article DOI: 10.1016/j.lanepe.2022.100407.].

Risk Factors for and Risk of Peripheral Artery Disease in Swedish Individuals With Type 2 Diabetes: A Nationwide Register-Based Study.

OBJECTIVE: To investigate to what extent having control of peripheral artery disease (PAD) risk factors is associated with the risk of incident PAD in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 148,096 individuals with type 2 diabetes in the Swedish National Diabetes Register between 2005 and 2009 were included and matched with 320,066 control subjects on the basis of age, sex, and county. A few control subjects who developed type 2 diabetes after recruitment, during wash-in (<0.2%), were not censored but instead matched with two new control subjects. Individuals with type 2 diabetes were evaluated according to the number of PAD risk factors beyond recommended guideline levels at baseline, including LDL cholesterol, blood pressure, smoking, glycated hemoglobin, and estimated glomerular filtration rate. Incident PAD events were ascertained from 2006 to 2019. RESULTS: A graded association was observed between the number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes. The adjusted hazard ratio for PAD was 1.41 (95% CI 1.23-1.63) for those with type 2 diabetes with all PAD risk factors within target compared with control subjects matched for sex, age, and county but not risk factor status, in contrast with 9.28 (95% CI 3.62-23.79) for those with all five PAD risk factors not at target. CONCLUSIONS: A graded association was observed between increasing number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes.

Mortality in Patients With Ebstein Anomaly.

BACKGROUND: Low birth prevalence and referral bias constitute significant obstacles to elucidating the natural history of Ebstein anomaly (EA). OBJECTIVES: An extensive 2-country register-based collaboration was performed to investigate the mortality in patients with EA. METHODS: Patients born from 1970 to 2017 and diagnosed with EA were identified in Danish and Swedish nationwide medical registries. Each patient was matched by birth year and sex with 10 control subjects from the general population. Cumulative mortality and HR of mortality were computed using Kaplan-Meier failure function and Cox proportional regression model. RESULTS: The study included 530 patients with EA and 5,300 matched control subjects with a median follow-up of 11 years. In the EA cohort, 43% (228) underwent cardiac surgery. Cumulative mortality was lower for patients diagnosed in the modern era (the year 2000 and later) than for those diagnosed in the prior era (P < 0.001). Patients with isolated lesion displayed lower cumulative mortality than patients with complex lesions did (P < 0.001). Patients with a presumed mild EA anatomy displayed a 35-year cumulative mortality of 11% (vs 4% for the matched control subjects; P < 0.001), yielding an HR for mortality of 6.0 (95% CI: 2.7-13.6), whereas patients with presumed severe EA demonstrated an HR of 36.2 (95% CI: 15.5-84.4) compared with control subjects and a cumulative mortality of 18% 35 years following diagnosis. CONCLUSIONS: Mortality in patients with EA is high irrespective of presence of concomitant congenital cardiac malformations and time of diagnosis compared with the general population, but overall mortality has improved in the contemporary era.

Survival Trends in Children With Tetralogy of Fallot in Sweden From 1970 to 2017.

Importance: Mortality in patients with tetralogy of Fallot (TOF) has decreased substantially since the start of surgical correction of this abnormality in the 1950s. However, nationwide data in Sweden comparing survival trends among pediatric patients with TOF with the general population are still limited. Objective: To study survival trends in pediatric patients with TOF and compare them with matched controls. Design, Setting, and Participants: A Swedish registry-based, nationwide, matched cohort study was conducted; data were collected from national health registers from January 1, 1970, to December 31, 2017. Patients with a registered diagnosis of TOF as well as controls without TOF matched by birth year and sex were included in the study. Follow-up data were collected from birth to age 18 years, death, or the end of follow-up (December 31, 2017), whichever occurred first. Data analysis was performed from September 10 to December 20, 2022. Survival trends among patients with TOF were compared with matched controls using Cox proportional hazards regression and Kaplan-Meier survival analyses. Main Outcomes and Measures: All-cause mortality during childhood in patients with TOF and matched controls. Results: The population included 1848 patients (1064 [57.6%] males; mean [SD] age, 12.4 [6.7] years) with TOF and 16 354 matched controls. The number of patients who underwent congenital cardiac surgery (henceforth, surgery group) was 1527 (897 [58.7%] males). In the whole TOF population from birth until age 18 years, 286 patients (15.5%) died during a mean (SD) follow-up time of 12.4 (6.7) years. In the surgery group, 154 of 1527 patients (10.1%) died during a follow-up time of 13.6 (5.7) years with a mortality risk of 21.9 (95% CI, 16.2-29.7) compared with matched controls. When stratified by birth period, a substantial decrease in the mortality risk was noted in the surgery group, from 40.6 (95% CI, 21.9-75.4) in those born in the 1970s to 11.1 (95% CI, 3.4-36.4) in those born in the 2010s. Survival increased from 68.5% to 96.0%. The risk of mortality for surgery decreased from 0.52 in the 1979s to 0.19 in the 2010s. Conclusions and Relevance: The findings of this study suggest there has been substantial improvement in survival in children with TOF who underwent surgery from 1970 to 2017. However, the mortality rate is still significantly higher in this group compared with matched controls. Predictors of good and poor outcomes in this group need to be further explored, with the modifiable ones evaluated for further outcome improvements.

Risk of cancer in young and older patients with congenital heart disease and the excess risk of cancer by syndromes, organ transplantation and cardiac surgery: Swedish health registry study (1930-2017).

Background: Increasing survival of patients with congenital heart disease (CHD) will result in an increased risk of age-dependent acquired diseases later in life. We aimed to investigate the risk of cancer in young and older patients with CHD and to evaluate the excess risk of cancer by syndromes, organ transplantation and cardiac surgery. Methods: Patients with CHD born between 1930 and 2017 were identified using Swedish Health Registers. Each patient with CHD (n = 89,542) was matched by sex and birth year with ten controls without CHD (n = 890,472) from the Swedish Total Population Register. Findings: 4012 patients with CHD (4·5%) and 35,218 controls (4·0%) developed cancer. The median follow-up time was 58·8 (IQR 42·4-69·0) years. The overall cancer risk was 1·23 times higher (95% confidence interval (CI) 1·19-1·27) in patients with CHD compared with matched controls, and remained significant when patients with syndromes and organ transplant recipients were excluded. The risk of cancer was higher in all CHD age groups, and in patients that underwent cardiac surgery during the first year after birth (Hazard Ratio 1·83; 95% CI 1·32-2·54). The highest risk was found in children (0-17 years), HR 3·21 (95% CI 2·90-3·56). Interpretation: The cancer risk in patients with CHD was 23% higher than in matched controls without CHD. The highest risk was found in children and in the latest birth cohort (1990-2017). Funding: Funding by the Swedish state (Grant Number: 236611), the Swedish Research Council (Grant Number: 2019-00193), the Swedish Childhood Cancer Fund (Grant Number: SP2017-0012) and the Swedish Heart-Lung Foundation (Grant Number: 20190724).

Body iron stores had no impact on coronary heart disease outcomes: a middle-aged male cohort from the general population with 21-year follow-up.

BACKGROUND: Body iron stores (BISs) have been proposed to be related to the development of cardiovascular diseases. However, results from epidemiological studies are conflicting. Knowledge on the long-term impact of BIS on cardiovascular outcomes in the general population is lacking. PURPOSE: The aim of this study was to explore the relationship between BIS and coronary heart disease (CHD) including death due to CHD. METHODS: This investigation is part of 'The Study of Men Born in 1943', a longitudinal prospective study of men living in the city of Gothenburg, Sweden. This random population sample was examined in 1993 (all at 50 years of age at baseline). A medical examination was performed, and questionnaires were used to evaluate lifestyle factors. Biomarkers for iron stores (serum ferritin and serum transferrin receptor) was analysed from frozen blood samples in 2014. All hospital admissions were registered through national registers during the entire follow-up from 1993 to 2014. HRs were estimated by Cox proportional-hazard regression analyses. RESULTS: During the 21 years follow-up period, 120 participants (15.2%) developed CHD and 16 patients (2%) died due to CHD. The all-cause mortality was 15.2% (n=120) including 40 cardiovascular deaths (5.1%). In a multivariable Cox regression analysis, the daily smoking, hypertension and the increased resting heart rate was independent predictors of CHD, while no significant association was found between BIS and risk of CHD. CONCLUSIONS: In a cohort of middle-aged men from the general population with well validated and prospectively collected data, we did not find any association between serum ferritin or serum transferrin receptor as markers of BIS and CHD events after 21 years of follow-up. TRAIL REGISTRATION NUMBER: NCT03138122.

Cardiorenal function and survival in in-hospital cardiac arrest: A nationwide study of 22,819 cases.

BACKGROUND: We studied the association between cardiorenal function and survival, neurological outcome and trends in survival after in-hospital cardiac arrest (IHCA). METHODS: We included cases aged ≥ 18 years in the Swedish Cardiopulmonary Resuscitation Registry during 2008 to 2020. The CKD-EPI equation was used to calculate estimated glomerular filtration rate (eGFR). A history of heart failure was defined according to contemporary guideline criteria. Logistic regression was used to study survival. Neurological outcome was assessed using cerebral performance category (CPC). RESULTS: We studied 22,819 patients with IHCA. The 30-day survival was 19.3%, 16.6%, 22.5%, 28.8%, 39.3%, 44.8% and 38.4% in cases with eGFR < 15, 15-29, 30-44, 45-59, 60-89, 90-130 and 130-150 ml/min/1.73 m2, respectively. All eGFR levels below and above 90 ml/min/1.73 m2 were associated with increased mortality. Probability of survival at 30 days was 62% lower in cases with eGFR < 15 ml/min/1.73 m2, compared with normal kidney function. At every level of eGFR, presence of heart failure increased mortality markedly; patients without heart failure displayed higher mortality only at eGFR below 30 ml/min/1.73 m2. Among survivors with eGFR < 15 ml/min/1.73 m2, good neurological outcome was noted in 87.2%. Survival increased in most groups over time, but most for those with eGFR < 15 ml/min/1.73 m2, and least for those with normal eGFR. CONCLUSIONS: All eGFR levels below and above normal range are associated with increased mortality and this association is modified by the presence of heart failure. Neurological outcome is good in the majority of cases, across kidney function levels and survival is increasing.

Incremental changes in QRS duration as predictor for cardiovascular disease: a 21-year follow-up of a randomly selected general population.

The QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50-60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07-2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.

Mortality burden in patients born with Ebstein's anomaly: a 40-year nationwide cohort study.

AIMS: Survival rates for unoperated patients with Ebstein's anomaly (EA) are unknown. We estimated overall long-term mortality in operated and unoperated EA patients, compared with the general population in Sweden. METHODS AND RESULTS: Using national medical registries, Swedish individuals born 1970-93 and diagnosed with EA between 1970 and 2011 were included. The hazard ratio for overall mortality for EA patients (n = 216) vs. the matched comparison cohort (n = 2160) was 43.7 [95% confidence interval (CI): 24.8-82.5]. Mortality risk for EA patients (vs. controls) decreased as birth period progressed, with hazard ratios declining from 63.6 (95% CI: 26.3-191.8) for those born in the 1970s to 34.4 (95% CI: 15.8-83.1) for those born in the 1980s and 20.2 (95% CI: 1.6-632.5) for those born at the beginning of 1990s. The overall mortality hazard ratios for unoperated and operated patients with EA (vs. controls) were 30.2 (95% CI: 13.8-73.3) and 63.7 (95% CI: 28.1-172.5), respectively. The risk of mortality among unoperated EA patients (vs. controls) declined with progressing birth period, with hazard ratios declining from 58.4 (95% CI: 15.1-415.2) in the 1970s to 22.9 (95% CI: 8.0-75.3) in the 1980s and 10.2 (95% CI: 0.3-395.9) in the 1990s. CONCLUSION: Overall all-cause mortality for patients with EA declined dramatically from 64 times to 20 times that of controls without EA, from the 1970s to the early 1990s. Unoperated patients with EA had better survival than did operated patients, possibly reflecting the higher severity of disease or more severe associated cardiac defects in patients undergoing surgery.

Secular trends in cardiovascular risk factors among women aged 45-54 years in Gothenburg, Sweden, from 1980 to 2014.

BACKGROUND: A declining trend in mean cholesterol levels and smoking has been observed in high-income western countries during the last few decades, whereas obesity rates have increased. Simultaneously, mortality from coronary heart disease has decreased. The aim of the present study was to determine whether the trends in cardiovascular risk factors have continued in successive cohorts of middle-aged women over a period of 34 years. METHODS: Six population-based, cross-sectional samples of women (n = 2294) mean age: 49.8 years (range: 45-54), living in Gothenburg, Sweden, were investigated between 1980 and 2014. RESULTS: Body mass index (BMI) increased over time, with a mean BMI of 24.7 kg/m2 in 1980 to 25.7 kg/m2 in 2013-2014, corresponding to a weight gain of 4.5 kg, together with an increase in the proportion of obese individuals (BMI ≥ 30 kg/m2) from 10.4 to 16.6% (p = 0.0012). The proportion of smokers and women with hypertension decreased from 34.5 to 12.8% (p = 0.0006) and from 37.7 to 24.5% (p < 0.0001) respectively. Mean total serum cholesterol levels decreased from 6.23 (SD 1.09) mmol/L in 1980 to 5.43 (SD 0.98) mmol/L in 2013-2014 (p < 0.0001). Self-reported leisure time regular exercise increased from 7.8% in 1980 to 35.6% in 2013-2014 (p < 0.0001). For women born in 1963, the prevalence ratio of not having any of five major cardiovascular risk factors was 1.82 (95% confidence interval (CI) 1.38-2.41), compared with women born in 1925-1934. CONCLUSION: The trend towards increasing obesity, more leisure-time physical activity and less smoking remains, while the decrease in serum cholesterol appears to have abated.

High prevalence of cardiac dysfunction or overt heart failure in 71-year-old men: A 21-year follow-up of "The Study of men born in 1943".

BACKGROUND: Knowledge about long-term risk factors and the prevalence of heart failure stages in general population is limited. We aimed to study the prevalence of cardiac dysfunction and heart failure in 71-year-old men and potential risk factors in the past two decades. DESIGN: This research was based on a randomized selected population study with longitudinal follow-up. METHODS: A random sample of men born in 1943 in Gothenburg, Sweden were examined in 1993 (at 50 years of age) and re-examined 21 years later in 2014 (at 71 years of age). Cardiac dysfunction or heart failure was classified into four stages (A-D) according to American Heart Association/American College of Cardiology guidelines on heart failure. RESULTS: Of the 798 men examined in 1993 (overall cohort), 535 (67%) were re-examined in 2014 (echo cohort). In the echo cohort 122 (23%) men had normal cardiac function, 135 (25%) were at stage A, 207 (39%) men were at stage B, 66 (12%) men were at stage C, and five (1%) men were at stage D. Multivariable logistic regression demonstrated that elevated body mass index at 50 years old was the only independent risk factor for developing heart failure/cardiac dysfunction during the subsequent 21 years. For each unit (1 kg/m2) of increased body mass index, the odds ratio for stages C/D heart failure vs no heart failure/stage A increased by 1.20 (95% confidence interval, 1.11-1.31, p < 0.001), after adjustment for smoking, sedentary life style, systolic blood pressure, diabetes, and hyperlipidemia. CONCLUSION: In a random sample of men at 71 years of age, half presented with either cardiac dysfunction or clinical heart failure. High body mass index was associated with an increased risk for developing cardiac dysfunction or heart failure over a 21-year period.

Risk of Cancer Among Children and Young Adults With Congenital Heart Disease Compared With Healthy Controls.

Importance: Adult patients with congenital heart disease (CHD) have an increased incidence of cancer, presumably owing to repeated radiation exposure, genetic predisposition, or repeated stress factors during heart interventions. However, there are limited data on the risk of cancer in children and young adults with CHD compared with the general population. Objective: To determine the risk of developing cancer from birth to age 41 years among patients with CHD compared with healthy matched controls. Design, Setting, and Participants: This registry-based, matched, prospective cohort study in Sweden used data from the Patient and Cause of Death Registers. Successive cohorts of patients with CHD born from 1970 to 1979, 1980 to 1989, and 1990 to 1993 were identified. Each patient (n = 21 982) was matched for birth year, sex, and county with 10 controls without CHD from the general population (n = 219 816). Follow-up and comorbidity data were collected from 1970 until 2011. Data analysis began in September 2018 and concluded in February 2019. Main Outcomes and Measures: Risk of cancer among children and young adults with CHD and among healthy controls. Results: Among 21 982 individuals with CHD and 219 816 healthy matched controls, 428 patients with CHD (2.0%) and 2072 controls (0.9%) developed cancer. Among patients with CHD, the mean (SD) age at follow-up was 26.6 (8.4) years, and 11 332 participants (51.6%) were men. Among healthy controls, the mean (SD) age at follow-up was 28.5 (9.1) years, and 113 319 participants (51.6%) were men. By the age of 41 years, 1 of 50 patients with CHD developed cancer. The overall hazard ratio (HR) for cancer was 2.24 (95% CI, 2.01-2.48) in children and young adults with CHD compared with controls. Risk increased by each successive birth cohort to an HR of 3.37 (95% CI, 2.60-4.35) among those born from 1990 to 1993. The risk of cancer was similar in men and women with CHD (men: HR, 2.41; 95% CI, 2.08-2.79; women: HR, 2.08; 95% CI, 1.80-2.41). The HR for cancer among patients with CHD who underwent surgery was 1.95 (95% CI, 1.58-2.33) compared with controls; for patients with CHD who had not undergone surgery, the HR was 2.43 (95% CI, 2.12-2.76). According to a hierarchical classification, a significantly increased risk of cancer was found among patients with complex heart lesions, such as conotruncal defects (HR, 2.29; 95% CI, 1.62-3.25), compared with healthy controls. Conclusions and Relevance: Children and young adult patients with CHD had an increased risk of developing cancer compared with healthy matched controls, and the risk was significantly higher among patients with CHD from the most recent birth cohort. An increased risk of cancer in all CHD lesion groups was found, and a systematic screening for cancer could be considered for this at-risk group of patients.

Cardiovascular risk factors in adults with coarctation of the aorta.

BACKGROUND: The aging patient with adult congenital heart disease (ACHD) faces the risk of developing atherosclerotic disease. Patients with coarctation of the aorta (CoA) are especially vulnerable because of an inherent high risk of developing hypertension. However, data on the prevalence of other cardiovascular risk factors are scarce. Therefore, this study aimed to describe the prevalence of traditional cardiovascular risk factors (diabetes, hypertension, hyperlipidemia, smoking, obesity, and sedentary lifestyle) in adult patients with CoA. METHODS: Patients with CoA who were registered at the ACHD clinic in Gothenburg were asked to participate in a comprehensive cardiovascular risk assessment. This assessment included a glucose tolerance test, cholesterol profile, ambulatory blood pressure measurements, and a lifestyle questionnaire. RESULTS: A total of 72 patients participated. The median age was 43.5 years and 58.3% were men. Sixty-six (91.7%) patients had ≥one cardiovascular risk factor and 40.3% had ≥three risk factors. Three (4.2%) patients were newly diagnosed with diabetes or impaired glucose tolerance. More than half of the patients had hyperlipidemia (n = 42, 58.3%) and 35 patients (48.6%) were overweight or obese. Only three (4.2%) patients smoked regularly. Of the 60 patients who underwent 24-hour ambulatory blood pressure measurement, 33 (55.0%) were hypertensive. Of the 30 patients with known hypertension only 9 (30.0%) had well-controlled blood pressure on ambulatory blood pressure measurement. CONCLUSIONS: Cardiovascular risk factors among patients with CoA are prevalent. This may indicate a need for more aggressive screening strategies of traditional risk factors to minimize the risk of these patients also developing atherosclerotic disease.

Natriuretic and Inflammatory Biomarkers as Risk Predictors of Heart Failure in Middle-Aged Men From the General Population: A 21-Year Follow-Up.

BACKGROUND: Although several biomarkers, including natriuretic peptides and inflammatory biomarkers, have proven to be useful prognostic predictors in patients with heart failure (HF), their predictive value for incident HF has not been extensively studied. METHODS AND RESULTS: The "Study of Men Born in 1943" is a longitudinal, prospective study of men living in the city of Gothenburg, Sweden. A panel of biomarkers consisting of interleukin-6 (IL-6), cystatin C, high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) was analyzed from blood samples collected in 1993 in men aged 50 years. Incident HF was recorded from multiple sources, including an echocardiographic assessment in 2014. A total of 747 (94%) of the 798 participants with no previous history of HF were included. Of these 747 participants, 85 (11.4%) developed HF over a 21-year follow-up. After adjustment for body mass index (BMI) and hypertension at baseline, NT-proBNP ≥25 ng/L was associated with a higher risk of HF (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.30-3.36; P = .0024), as was hs-CRP >3 mg/L (OR 2.61, 95% CI 1.59-4.29; P = .0002). In a multivariable model, the expected probability of HF was 0.33 (95% CI 0.23-0.45) in hypertensive patients with hs-CRP >3 mg/L, NT-proBNP ≥25 ng/L, and BMI ≥25 kg/m2, compared with a probability of 0.04 (95% CI 0.02-0.07) in nonhypertensive patients with hs-CRP ≤3 mg/L, NT-proBNP <25 ng/L, and BMI <25 kg/m.2 CONCLUSIONS: NT-proBNP ≥25 ng/L and elevated hs-CRP levels in men aged 50 years were predictive biomarkers for HF over a 2one year follow-up.

Although Coronary Mortality Has Decreased, Rates of Cardiovascular Disease Remain High: 21 Years of Follow-Up Comparing Cohorts of Men Born in 1913 With Men Born in 1943.

BACKGROUND: Despite a decline in mortality rates from cardiovascular disease (CVD) in the past few decades, the burden of CVD in a contemporary population remains inadequately addressed. Therefore, this study was aimed to investigate secular trends in mortality from coronary artery disease and all-cause mortality over 2 decades, by comparing 2 cohorts of men born 30 years apart and evaluate the prediction of the risk of CVD and all-cause death in a contemporary random sample of Swedish men. METHODS AND RESULTS: Two cohorts of randomly selected men born in 1913 (855 men) and 1943 (798 men) were first examined at age 50 in 1963 and 1993, respectively, and followed longitudinally over 21 years. All-cause mortality and coronary artery disease death were lower in 50- to 71-year-old men born in 1943 compared with those born in 1913, with unadjusted hazard ratios of 0.57 (0.45-0.71) and 0.34 (0.22-0.53), respectively. After adjustment for risk factors (smoking, serum cholesterol, hypertension, systolic blood pressure, diabetes mellitus, body mass index, and physical activity), the differences between the cohorts remained significant for coronary artery disease, hazard ratios 0.57 (0.34-0.94), P=0.029, but not for all-cause mortality hazard ratios 0.82 (0.62-1.07), P=0.14. However, the rate of CVD events during follow-up was still high (30.7%) for the men born in 1943. No statistically significant interaction by birth cohort in contribution of risk factors to death was found between 2 cohorts except physical inactivity. CONCLUSIONS: Despite a marked reduction in the rate of coronary artery disease death over the past 30 years, the burden of CVD events and all-cause mortality remains high. Therefore, intensified efforts to modify contributing risk factors are still required.

Atrial Fibrillation Burden in Young Patients With Congenital Heart Disease.

BACKGROUND: Patients with congenital heart disease (CHD) are assumed to be vulnerable to atrial fibrillation (AF) as a result of residual shunts, anomalous vessel anatomy, progressive valvulopathy, hypertension, and atrial scars from previous heart surgery. However, the risk of developing AF and the complications associated with AF in children and young adults with CHD have not been compared with those in control subjects. METHODS: Data from the Swedish Patient and Cause of Death registers were used to identify all patients with a diagnosis of CHD who were born from 1970 to 1993. Each patient with CHD was matched by birth year, sex, and county with 10 control subjects from the Total Population Register in Sweden. Follow-up data were collected until 2011. RESULTS: Among 21 982 patients (51.6% men) with CHD and 219 816 matched control subjects, 654 and 328 developed AF, respectively. The mean follow-up was 27 years. The risk of developing AF was 21.99 times higher (95% confidence interval, 19.26-25.12) in patients with CHD than control subjects. According to a hierarchical CHD classification, patients with conotruncal defects had the highest risk (hazard ratio, 84.27; 95% confidence interval, 56.86-124.89). At the age of 42 years, 8.3% of all patients with CHD had a recorded diagnosis of AF. Heart failure was the quantitatively most important complication in patients with CHD and AF, with a 10.7% (70 of 654) recorded diagnosis of heart failure. CONCLUSIONS: The risk of AF in children and young adults with CHD was 22 times higher than that in matched control subjects. Up to the age of 42 years, 1 of 12 patients with CHD had developed AF, and 1 of 10 patients with CHD with AF had developed heart failure. The patient groups with the most complex congenital defects carried the greatest risk of AF and could be considered for targeted monitoring.

Secular changes in cardiovascular risk factors in Swedish 50-year-old men over a 50-year period: The study of men born in 1913, 1923, 1933, 1943, 1953 and 1963.

Background During the past decades, declining trends in mean cholesterol levels and smoking have been observed in Western Europe, whereas obesity and a sedentary lifestyle have increased. Simultaneously, there has been a marked decrease in mortality from cardiovascular (CV) diseases. Methods The aim of the study was to determine whether these trends in CV risk factors continued over a period of 50 years. Six systematic or random population samples of 50-year-old men ( n = 3563) living in Gothenburg, Sweden, were investigated between 1963 and 2013. Results During the 50 years, mean body mass index (BMI) at 50 years of age increased by 2 kg/m2, from 24.8 kg/m2 in 1963 to 26.8 kg/m2 in 2013 ( p < 0.001). A decrease in systolic blood pressure of nearly 10 mmHg was observed from 1963 to 1993, but was not sustained through the past two decades. Mean serum cholesterol fell from 6.42 (SD 1.12) mmol/L to 5.34 (SD 0.97) mmol/L. The prevalence of smoking at 50 years of age decreased markedly from 56.1% in 1963 to 11.9% in 2013. The number of participants with a sedentary lifestyle during leisure time decreased until 1993, but has remained unchanged since. In 2013, 50-year-old men had a 6.9-times higher likelihood of lacking CV risk factors than 50-year-old men in 1963 (95% confidence interval (CI): 3.5-13.3, p < 0.001). The odds ratio for having four or more risk factors was only 0.13 (95% CI: 0.062-0.29, p < 0.001). Conclusion Despite increasing body weight, the total CV risk factor burden has decreased in 50-year-old men over the past 50 years.

Low aerobic capacity in middle-aged men associated with increased mortality rates during 45 years of follow-up.

BACKGROUND: Low aerobic capacity has been associated with increased mortality in short-term studies. The aim of this study was to evaluate the predictive power of aerobic capacity for mortality in middle-aged men during 45-years of follow-up. DESIGN: The study design was a population-based prospective cohort study. METHODS: A representative sample from Gothenburg of men born in 1913 was followed from 50-99 years of age, with periodic medical examinations and data from the National Hospital Discharge and Cause of Death registers. At 54 years of age, 792 men performed an ergometer exercise test, with 656 (83%) performing the maximum exercise test. RESULTS: In Cox regression analysis, low predicted peak oxygen uptake ([Formula: see text]), smoking, high serum cholesterol and high mean arterial blood pressure at rest were significantly associated with mortality. In multivariable analysis, an association was found between predicted [Formula: see text] tertiles and mortality, independent of established risk factors. Hazard ratios were 0.79 (95% confidence interval (CI) 0.71-0.89; p < 0.0001) for predicted [Formula: see text], 1.01 (1.002-1.02; p < 0.01) for mean arterial blood pressure, 1.13 (1.04-1.22; p < 0.005) for cholesterol, and 1.58 (1.34-1.85; p < 0.0001) for smoking. The variable impact (Wald's χ(2)) of predicted [Formula: see text] tertiles (15.3) on mortality was secondary only to smoking (31.4). The risk associated with low predicted [Formula: see text] was evident throughout four decades of follow-up. CONCLUSION: In this representative population sample of middle-aged men, low aerobic capacity was associated with increased mortality rates, independent of traditional risk factors, including smoking, blood pressure and serum cholesterol, during more than 40 years of follow-up.