High-normal blood pressure conferred higher risk of cardiovascular disease in a random population sample of 50-year-old men: A 21-year follow-up.

The relationship between various categories of blood pressure (BP), subtypes of hypertension, and development of cardiovascular disease (CVD) have not been extensively studied. Therefore, our study aimed to explore this relationship in a random population sample of men born in 1943, living in Sweden and followed over a 21-year period.Participants were examined for the first time in 1993 (age 50 years), where data on medical history, concomitant diseases, and general health were collected. The examination was repeated in 2003 and with additional echocardiography also in 2014. Classification of participants according to their BP at the age of 50 years was as follows: optimal-normal BP (systolic blood pressure [SBP] <130 and diastolic BP [DBP] <85 mmHg), high-normal BP (130 ≤ SBP < 140, 85 ≤ DBP < 90 mmHg), isolated systolic-diastolic hypertension (ISH-IDH) (SBP ≥140 and DBP <90 or SBP <140 and DBP ≥90 mmHg), and systolic-diastolic hypertension (SDH) (SBP ≥140 and DBP ≥90 mmHg).During the follow-up, the incidence of heart failure (HF), CVD, and coronary heart disease were all lowest for those with optimal-normal BP. Participants with high-normal BP showed greater wall thickness and left ventricular mass index, larger LV size and larger left atrial size when compared with the optimal-normal BP group. Furthermore, those with high-normal BP, ISH-IDH, and SDH had a higher risk of CVD than those with optimal-normal BP. The adjusted relative risk of CVD was highest for SDH (hazard ratio [HR] 1.95; 95% confidence interval [95% CI] 1.37-2.79), followed by ISH-IDH (HR 1.34; 95% CI 0.93-1.95) and high-normal BP (HR 1.31; 95% CI 0.91-1.89).Over a 21-year follow-up, the participants with high-normal BP or ISH-IDH had a higher relative risk of CVD than those with optimal-normal BP.

Comparison of incidence rates and risk factors of heart failure between two male cohorts born 30 years apart.

OBJECTIVE: To compare two cohorts of middle-aged men from the general population born 30 years apart for incidence and predictors of heart failure (HF). METHODS: Two population samples of men, born in 1913 (n=855) and in 1943 (n=797), were examined at 50 years of age and followed up for 21 years (1963-1994 and 1993-2014). Cox regression analysis was used to examine the impact of different factors on the risk of developing HF. RESULTS: Eighty men born in 1913 (9.4%) and 42 men born in 1943 (5.3%) developed HF during follow-up; adjusted HRs comparing the two cohorts (born 1943 vs 1913) were: 0.46 (95% CI 0.28 to 0.74, p=0.002). In both cohorts, higher body mass index, higher diastolic blood pressure, treatment for hypertension, onset of either atrial fibrillation (AF), ischaemic heart disease and diabetes mellitus were associated with higher risk of HF. Higher heart rate was associated with an increased risk only in men born in 1913, whereas higher systolic blood pressure (SBP), smoking, higher glucose, higher cholesterol and physical inactivity were associated with an increased risk in men born in 1943. AF contributed higher risk of incident HF, whereas SBP and physical inactivity contributed lower risk in men born in 1943 compared with men born in 1913. CONCLUSIONS: Men born in 1943 had half the risk of HF after their 50s than those born 30 years earlier. AF, obesity, ischaemic heart disease, diabetes and hypertension remain important precursors of HF.

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.

Prevalence and risk factors of aortic stenosis and aortic sclerosis: a 21-year follow-up of middle-aged men.

Introduction. There is limited knowledge about factors associated with the development of aortic stenosis. This study aimed to examine the prevalence of aortic sclerosis or stenosis in 71-years-old men and determine which risk factors at 50 years of age predict the development of aortic sclerosis or aortic stenosis. Methods. A random sample of Swedish men from the general population, born in 1943 (n = 798) were followed for 21 years. Data on clinical characteristics and laboratory values were collected in 1993. An echocardiography was performed in 2014. We used logistic regression to examine the association between baseline data and the outcome. Results. Echocardiography was performed in 535 men, and aortic sclerosis or aortic stenosis was diagnosed in 27 (5.0%). 14 persons developed aortic stenosis (2.6%). Among men with aortic sclerosis or aortic stenosis, 29.6% were obese. In multivariable stepwise regression model, body mass index (odds ratio per unit increase 1.23 (95% CI 1.10-1.38; p = .0003)) and hypercholesterolemia, combined with high sensitive C-reactive protein (odds ratio versus all other 2.66 (1.18-6.00; p = .019)) were significantly associated with increased risk of developing aortic sclerosis or aortic stenosis. Body mass index was the only factor significantly associated with a higher risk of developing aortic stenosis. Conclusion. The prevalence of either aortic sclerosis or aortic stenosis was 5% and of aortic stenosis 2.6%. Obesity and hypercholesterolemia combined with elevated high sensitive C-reactive protein at the age of 50 predicted the development of degenerative aortic sclerosis or stenosis, whilst only obesity was correlated with the occurrence of aortic stenosis.

Impact of changes in heart rate with age on all-cause death and cardiovascular events in 50-year-old men from the general population.

Background: Resting heart rate (RHR), a known cardiovascular risk factor, changes with age. However, little is known about the association between changes in RHR and the risk of cardiovascular events. The purpose of this study was therefore to assess the impact of RHR at baseline, and the change in RHR over time, on the risk of all-cause death and cardiovascular events. Design: A random population sample of men born in 1943 who were living in Gothenburg, Sweden was prospectively followed for a 21-year period. Methods: Participants were examined three times: first in 1993 and then re-examined in 2003 and 2014. At each visit, a clinical examination, an ECG and laboratory analyses were performed. Change in RHR between 1993 and 2003 was defined as a decrease if RHR decreased by 5 beats per minute (bpm), an increase if RHR increased by 5 bpm or stable if the RHR change was <4bpm). Results: Participants with a baseline RHR of >75 bpm in 1993 had about a twofold higher risk of all-cause death (HR 2.3, CI 1.2 to 4.7, p=0.018), cardiovascular disease (CVD) (HR 1.8, CI 1.1 to 3.0, p=0.014) and coronary heart disease (CHD) (HR 2.2, CI 1.1 to 4.5, p=0.025) compared with those with <55 bpm in 1993. Participants with a stable RHR between 1993 and 2003 had a 44% decreased risk of CVD (HR 0.56, CI 0.35 to 0.87, p=0.011) compared with participants with an increasing RHR. Furthermore, every beat increase in heart rate from 1993 was associated with a 3% higher risk for all-cause death, 1% higher risk for CVD and 2% higher risk for CHD. Conclusion: High RHR was associated with an increased risk of death and cardiovascular events in men from the general population. Moreover, individuals with an increase in RHR between 50 and 60 years of age had worse outcome.

Non-cardiac comorbidities and mortality in patients with heart failure with reduced vs. preserved ejection fraction: a study using the Swedish Heart Failure Registry.

BACKGROUND: Heart failure (HF) and non-cardiac comorbidities often coexist and are known to have an adverse effect on outcome. However, the prevalence and prognostic impact of non-cardiac comorbidities in patients with HF with reduced ejection fraction (HFrEF) vs. those with preserved (HFpEF) remain inadequately studied. METHODS AND RESULTS: We used data from the Swedish Heart Failure Registry from 2000 to 2012. HFrEF was defined as EF < 50% and HFpEF as EF ≥ 50%. Of 31 344 patients available for analysis, 79.3% (n = 24 856) had HFrEF and 20.7% (n = 6 488) HFpEF. The outcome was all-cause mortality. We examined the association between ten non-cardiac comorbidities and mortality and its interaction with EF using adjusted hazard ratio (HR). Stroke, anemia, gout and cancer had a similar impact on mortality in both phenotypes, whereas diabetes (HR 1.57, 95% confidence interval [CI] [1.50-1.65] vs. HR 1.39 95% CI [1.27-1.51], p = 0.0002), renal failure (HR 1.65, 95% CI [1.57-1.73] vs. HR 1.44, 95% CI [1.32-1.57], p = 0.003) and liver disease (HR 2.13, 95% CI [1.83-2.47] vs. HR 1.42, 95% CI [1.09-1.85] p = 0.02) had a higher impact in the HFrEF patients. Moreover, pulmonary disease (HR 1.46, 95% CI [1.40-1.53] vs. HR 1.66 95% CI [1.54-1.80], p = 0.007) was more prominent in the HFpEF patients. Sleep apnea was not associated with worse prognosis in either group. No significant variation was found in the impact over the 12-year study period. CONCLUSIONS: Non-cardiac comorbidities contribute significantly but differently to mortality, both in HFrEF and HFpEF. No significant variation was found in the impact over the 12-year study period. These results emphasize the importance of including the management of comorbidities as a part of a standardized heart failure care in both HF phenotypes.

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.

Association between left atrial enlargement and obstructive sleep apnea in a general population of 71-year-old men.

Left atrial enlargement has been shown to be associated with obstructive sleep apnea in patients with coronary artery disease and in sleep clinic cohorts. However, data from the general population are limited. The aim of this study was to investigate whether there is an association between obstructive sleep apnea and left atrial enlargement in a random sample from a general population of 71-year-old men. As part of the longitudinal population study The Study of Men Born in 1943, we analysed cross-sectional data for 411 men, all 71 years old, who had participated in an overnight home sleep study and a standardized echocardiographic examination. Of the 411 men, 29.4% had moderate to severe obstructive sleep apnea [apnea-hypopnea index score of ≥15 (n = 121)]. These participants showed a significantly higher frequency of systolic heart failure, hypertension, overweight, had greater waist circumference as well as higher left atrial areas compared with men with no or mild obstructive sleep apnea (23.7 ± 5.5 cm2 versus 21.6 ± 4.5 cm2 , P < 0.001). In a linear regression analysis, obstructive sleep apnea was significantly associated with left atrial enlargement after adjusting for overweight, atrial fibrillation, heart failure with reduced ejection fraction, hypertension and mitral regurgitation. Compared with individuals without obstructive sleep apnea, the mean left atrial area was 1.7 ± 1.5 cm2 larger in men with severe obstructive sleep apnea (P < 0.05) and 1.3 ± 1.1 cm2 larger among men with moderate obstructive sleep apnea (P < 0.05). In this cross-sectional study of 71-year-old men from the general population, left atrial area was independently associated with prevalence and severity of obstructive sleep apnea.

Long-term secondary prevention of acute myocardial infarction (SEPAT) - guidelines adherence and outcome.

BACKGROUND: A number of registry studies have reported suboptimal adherence to guidelines for cardiovascular prevention during the first year after acute myocardial infarction (AMI). However, only a few studies have addressed long-term secondary prevention after AMI. This study evaluates prevention guideline adherence and outcome of guideline-directed secondary prevention in patients surviving 2 years after AMI. METHODS: Patients aged 18-85 years at the time of their index AMI were consecutively identified from hospital discharge records between July 2010 and December 2011 in Gothenburg, Sweden. All patients who agreed to participate in the study (16.2%) were invited for a structured interview, physical examinations and laboratory analysis 2 years after AMI. Guideline-directed secondary preventive goals were defined as optimally controlled blood pressure, serum cholesterol, glucose, regular physical activity, smoking cessation and pharmacological treatment. RESULTS: The mean age of the study cohort (n = 200) at the index AMI was 63.0 ± 9.7 years, 79% were men. Only 3.5% of the cohort achieved all six guideline-directed secondary preventive goals 2 years after infarction. LDL < 1.8 mmol/L was achieved in 18.5% of the cohort, regular exercise in 45.5% and systolic blood pressure <140 mmHg in 57.0%. Anti-platelet therapy was used by 97% of the patients, beta-blockers by 83.0%, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers by 76.5% and statins by 88.5%. During follow-up, non-fatal adverse cardiovascular events (cardiac hospitalization, recurrent acute coronary syndrome, angina pectoris, new percutaneous coronary intervention, new onset of atrial fibrillation, post-infarct heart failure, pacemaker implantation, stroke/transient ischemic attack (TIA), cardiac surgery and cardiac arrest) occurred in 47% of the cohort and readmission due to cardiac causes in 30%. CONCLUSIONS: Our data showed the failure of secondary prevention in our daily clinical practice and high rate of non-fatal adverse cardiovascular events 2 years after AMI.

Does the target dose of neurohormonal blockade matter for outcome in Systolic heart failure in octogenarians?

BACKGROUND: In elderly patients with chronic heart failure (CHF), a gap exists between widespread use of lower doses of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) and ß-blockers (BBs) and guideline recommendations. Therefore, the aim of the present study was to investigate whether patients receiving ≥ 50% target dose outperform those receiving <50% target dose, despite maximum up-titration, and whether the target dose outperforms all other doses. METHODS AND RESULTS: Patients (n=185) aged ≥ 80 years with CHF and left ventricular ejection fraction ≤ 40% referred (between January 2000 and January 2008) to two CHF outpatient clinics at two university hospitals, were included and retrospectively studied. Of the study population, 53% received the target dose of ACEIs/ARBs, whereas 26% received <50% of the target dose. Half received <50% of the target dose of BBs and 21% received the target dose. After ≥ 5 years of follow-up, all-cause mortality was 76.8%. Patients who received the target dose of ACEIs/ARBs had higher survival rates from all-cause mortality than those receiving <50% of target dose (HR=0.6, 95%CI 0.4-0.9, P=0.033), but those receiving ≥ 50% of target dose did not statistically differ from those who achieved target dose. This dose-survival relationship was not the case for BBs. CONCLUSIONS: Target dose of ACEIs/ARBs is associated with reduced all-cause five-year mortality in very old patients with systolic heart failure, despite that this was achievable in only about half of the patients. However, the clinical outcome of BB therapy is independent of BB dose when the target heart rate is achieved.