Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.

Importance: Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown. Objective: To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening. Design, Setting, and Participants: Cross-sectional study of a population-based cohort of women in Sweden (n = 10 528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected. Exposures: Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures. Main Outcomes and Measures: Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100. Results: A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk. Conclusions and Relevance: Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.

Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events: A Meta-Analysis.

Importance: The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated. Objective: To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials. Data Sources: PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023. Study Selection: For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included. Data Extraction and Synthesis: Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]). Main Outcomes and Measures: One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day). Results: A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]). Conclusions and Relevance: Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.

Mid-life extrapyramidal symptoms predict cognitive impairment 23 years later.

OBJECTIVES: The prevalence of dementia is growing rapidly worldwide. The early identification and treatment of cognitive decline could reduce the burden on the health care system. Our objective was to investigate whether factors measured at an examination at age 50 predict cognitive impairment (CI) 23 years later. MATERIALS & METHODS: In 1993 we enrolled a randomly selected sample of 798 men, 50 years of age, from the general population. They all underwent a physical examination, provided blood samples and filled out questionnaires addressing lifestyle and psychosocial factors. Cognitive testing was offered to all participants still alive in 2016, at age 73. RESULTS: A total of 333 men participated in the cognitive study, of which 80 (24.0%) performed at a level corresponding to mild cognitive impairment, and four (1.2%) at a level consistent with severe cognitive impairment. After the first step in the multivariable analysis, hypertension, heavy smoking, high intake of alcohol, financial stress, difficulty falling asleep, and cogwheel rigidity were associated with cognitive impairment. After further adjustment, only wide waist circumference measured in cm (OR 1.04, 95% CI 1.00-1.08, p = .04), leg pendulousness (OR 41.97, 95% CI 3.27-538.62, p = .004) and self-assessed hidden irritability (OR 2.18, 95% CI 1.10-4.32, p = .03) at baseline, remained as being associated with cognitive impairment 23 years later. CONCLUSIONS: Extrapyramidal symptoms such as leg pendulousness, at the age of 50, may be an indicator for very early identification of future cognitive decline.

Cumulative incidence and predictors of acquired aortic stenosis in a large population of men followed for up to 43 years.

BACKGROUND: Acquired aortic stenosis (AS) increases with age and has high mortality without intervention. Factors predicting its development are unclear, although atherosclerotic factors are assumed to be involved. Our aim in this study is to estimate the lifetime cumulative incidence and predictors of AS in middle-aged men. METHODS: We included a random sample of men (n = 9998) born 1915-1925 in Gothenburg, Sweden. From them, 7,494 were examined and followed until a diagnosis of AS or death (maximum follow-up time 42.8 years). We identified AS diagnosis from the Swedish National Patient Registry and deaths from the Swedish Cause of Death Registry by using International Classification of Disease (ICD) diagnostic criteria. To study time-dependent relationships between AS and risk factors with death as the competing risk, we divided the cohort into three overlapping follow-up groups: 25-43, 30-43 and 35-43 years. We used age-adjusted Cox proportional hazards model to identify predictors of AS. RESULTS: The lifelong cumulative incidence of AS was 3.2%. At baseline, participants in the third group had a healthier lifestyle, lower body mass index (BMI), blood pressure, and serum cholesterol levels. Higher BMI, obesity, cholesterol, hypertension, atrial fibrillation, smoking and heredity for stroke were associated with AS. With BMI of 20-22.5 as a reference, hazard ratios of being diagnosed with AS for men with a baseline BMI of 25-27.5 kg/m2, 27.5-30 kg/m2 and > 30 kg/m2 were 1.99 (95% CI 1.12-3.55), 2.98 (95% CI 1.65-5.40) and 3.55 (95% CI 1.84-6.87), respectively. CONCLUSIONS: The lifetime cumulative incidence of AS in middle-aged male population was 3.2%. Multiple atherosclerotic risk factors, particularly high BMI might be associated with a higher risk of developing AS.

Multi-modality biomarkers in the early prediction of ischaemic heart disease in middle-aged men during a 21-year follow-up.

BACKGROUND: Ischaemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. Biomarkers are useful prognostic predictors of IHD, but their long-term predictive value in a general population has not been adequately studied. PURPOSE: To investigate the early predictive value of multi-modality biomarkers in addition to clinical risk factors in incident IHD in a random male general population sample followed from 50 to 71 years of age. METHOD: "The Study of Men Born in 1943" is a longitudinal cohort study during follow-up. All the men underwent a baseline examination in 1993, where a panel of biomarkers were analysed and incident IHD was registered during 21-year follow-ups. RESULTS: Of 739 participants, 97 men (13.1%) developed an IHD event. For time to first occurrence of IHD, univariable analyses showed that elevated levels of high sensitivity troponin T (hs-TNT), high sensitivity-C reactive protein (hs-CRP) and interleukin-6 (IL-6) were significant predictors of IHD. In addition, a high number of biomarkers with elevated levels (hs-TNT > 10 ng/L, hs-CRP > 1 mg/L, IL-6 > 8 ng/L and N-terminal pro b-type natriuretic peptide (NT-proBNP) > 100 pg/mL) increased predictive ability. In univariable and multivariable analysis high-density lipoprotein-cholesterol (HDL-C) had the highest predictive ability. Hs-TNT provided better predictive ability than smoking, body mass index and glucose, and was an independent significant predictor when adjusted for HDL-C, total cholesterol and hypertension. Addition of biomarkers on top of clinical risk factors provided significantly better prediction as tested by likelihood ratio test (p = 0.033), but did not significantly enhance the model's discriminative ability However, it appeared contributing to higher sensitivity in the late phase of follow-up. CONCLUSION: In this random, middle-aged male population sample, the addition of biomarker hs-TNT was an independent significant predictor of IHD and significantly improved prediction, indicating the probability of a better prediction of long-term risk of IHD in a low-risk population. TRIAL REGISTRATION: The study is registered at Clinical Trials.gov Identifier number: NCT03138122.

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.

Determinants of depressive mood in coronary artery disease patients with obstructive sleep apnea and response to continuous positive airway pressure treatment in non-sleepy and sleepy phenotypes in the RICCADSA cohort.

We explored determinants of depressive mood in adults with coronary artery disease and obstructive sleep apnea and response to positive airway pressure treatment in sleepy and non-sleepy phenotypes. In this secondary analysis of the RICCADSA trial conducted in Sweden, 493 cardiac patients with obstructive sleep apnea (n = 386) or no obstructive sleep apnea (n = 107) with complete Epworth Sleepiness Scale and Zung Self-rating Depression Scale questionnaires were included. Sleepy (Epworth Sleepiness Scale ≥10) versus non-sleepy (Epworth Sleepiness Scale <10) patients with depressive mood (Zung Self-rating Depression Scale score ≥50) were evaluated after 3 and 12 months of positive airway pressure treatment. In all, 133 patients (27.0%) had depressive mood (29.3% of obstructive sleep apnea versus 18.7% of no obstructive sleep apnea; p = 0.029), with a higher percentage among the sleepy phenotype (36.9% versus 24.5%; p = 0.009). In multivariate analysis, depressive mood was significantly associated with female sex, body mass index and Epworth Sleepiness Scale. Among 97 obstructive sleep apnea patients with depressive mood at baseline, there was a significant reduction in the scores at follow-up both in the sleepy and non-sleepy patients allocated to positive airway pressure treatment, whereas no significant changes were observed in the untreated group (p = 0.033). The device use (hr/night) predicted improvement in mood (odds ratio, 1.33; 95% confidence interval, 1.10-1.61; p = 0.003) adjusted for age, female sex, body mass index, left ventricular ejection fraction, apnea-hypopnea index and delta Epworth Sleepiness Scale score. We conclude that obstructive sleep apnea was associated with depressive mood in adults with coronary artery disease. Treatment with positive airway pressure improved mood in both phenotypes, independent of the confounding factors.

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.

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.

The incidence of atrial fibrillation and the added value of thumb ECG for detecting new cases.

OBJECTIVES: To evaluate the incidence of atrial fibrillation (AF) as well as the value of thumb electrocardiography (ECG) for identification of paroxysmal AF in a Swedish cohort of middle-aged men from the general population. DESIGN: A population based random cohort of 798 men underwent screening at the age of 50 and re-examined at the age of 60 and 71 years. At the last examination, a thumb ECG recording was conducted for 2 weeks twice a day in 479 men from the original cohort. Registered hospital AF diagnoses were retrieved from the Swedish Patient Registry from 1993 to 2014. RESULTS: During a 21-year follow-up, 77 men (9.6%) were diagnosed with AF; of these men, 49.4% (38 of 77) had permanent AF. Fifteen of 479 (3.1%) patients had paroxysmal AF. Of those, seven had been previously diagnosed with paroxysmal AF through Patient Registry. The incidence of AF increased from 2.2 per 1000 years at risk at the age of 50-54 years to 9.3 per 1000 years at risk at the age 65-70 years. The prevalence of AF at the age of 71 years was increased from 7.1% to 9.9% using thumb ECG. CONCLUSIONS: In addition to medical history, patient register and 12-lead -ECG, the use of thumb ECG increased the number of detected paroxysmal AF by 21%.

Obstructive sleep apnea and self-reported functional impairment in revascularized patients with coronary artery disease in the RICCADSA trial.

PURPOSE: Daytime sleepiness, a frequent symptom of obstructive sleep apnea (OSA), can impact functional status. In patients with coronary artery disease (CAD) and concomitant OSA, the distinction between sleep-related functional impairment from underlying CAD versus OSA is unclear. This study evaluated the impact of OSA on sleep-related functional impairment in patients with CAD and compared the effect of 1-year continuous positive airway pressure (CPAP) use on change in impairment between those with and without excessive daytime sleepiness (EDS) and OSA. We hypothesized that sleep-related functional impairment is impacted by EDS independent of OSA in patients with CAD. METHODS: One hundred five CAD patients without OSA and 105 with moderate-to-severe OSA from the RICCADSA trial were matched on disease severity and included in the current substudy. Of those with OSA, 80 were allocated to CPAP. Functional Outcomes of Sleep Questionnaire (FOSQ) score < 17.9 corresponded to sleep-related functional impairment. RESULTS: Following revascularization, CAD patients with and without OSA frequently report sleep-related functional impairment (35% and 27.3%, respectively; p = .29). Moderate-to-severe OSA was not related to baseline FOSQ scores < 17.9 in regression analyses; EDS was (OR 4.82, 95% CI 2.12-11.0; p < .001). CPAP use significantly improved FOSQ scores from baseline to 1-year follow-up in OSA patients with EDS (17.2 ± 2.0 to 18.15 ± 1.7, p = .002) despite suboptimal adherence. CONCLUSIONS: Sleep-related functional impairment may be reflective of persistent EDS, independent of OSA. Diagnosing OSA and initiating treatment are worthwhile in individuals with CAD and EDS, as both are important to guide appropriate therapy in patients with CAD.

Outcomes in coronary artery disease patients with sleepy obstructive sleep apnoea on CPAP.

Coronary artery disease (CAD) patients with obstructive sleep apnoea (OSA) have increased risk for major adverse cardiovascular and cerebrovascular events (MACCEs) compared with CAD patients without OSA. We aimed to address if the risk is similar in both groups when OSA patients are treated.This study was a parallel observational arm of the RICCADSA randomised controlled trial, conducted in Sweden between 2005 and 2013. Patients with revascularised CAD and OSA (apnoea-hypopnoea index (AHI) ≥15 events·h-1) with daytime sleepiness (Epworth Sleepiness Scale score ≥10) were offered continuous positive airway pressure (CPAP) (n=155); CAD patients with no OSA (AHI <5 events·h-1) acted as controls (n=112), as a randomisation of sleepy OSA patients to no treatment would not be ethically feasible. The primary end-point was the first event of MACCEs. Median follow-up was 57 months.The incidence of MACCEs was 23.2% in OSA patients versus 16.1% in those with no OSA (adjusted hazard ratio 0.96, 95% CI 0.40-2.31; p=0.923). Age and previous revascularisation were associated with increased risk for MACCEs, whereas coronary artery bypass grafting at baseline was associated with reduced risk.We conclude that the risk for MACCEs was not increased in CAD patients with sleepy OSA on CPAP compared with patients without OSA.

Blood Pressure Response to Losartan and Continuous Positive Airway Pressure in Hypertension and Obstructive Sleep Apnea.

RATIONALE: Obstructive sleep apnea (OSA) is common in people with hypertension, particularly resistant hypertension. Treatment with an antihypertensive agent alone is often insufficient to control hypertension in patients with OSA. OBJECTIVES: To determine whether continuous positive airway pressure (CPAP) added to treatment with an antihypertensive agent has an impact on blood pressure (BP) levels. METHODS: During the initial 6-week, two-center, open, prospective, case-control, parallel-design study (2:1; OSA/no-OSA), all patients began treatment with an angiotensin II receptor antagonist, losartan, 50 mg daily. In the second 6-week, sex-stratified, open, randomized, parallel-design study of the OSA group, all subjects continued to receive losartan and were randomly assigned to either nightly CPAP as add-on therapy or no CPAP. MEASUREMENTS AND MAIN RESULTS: Twenty-four-hour BP monitoring included assessment every 15 minutes during daytime hours and every 20 minutes during the night. Ninety-one patients with untreated hypertension underwent a home sleep study (55 were found to have OSA; 36 were not). Losartan significantly reduced systolic, diastolic, and mean arterial BP in both groups (without OSA: 12.6, 7.2, and 9.0 mm Hg; with OSA: 9.8, 5.7, and 6.1 mm Hg). Add-on CPAP treatment had no significant changes in 24-hour BP values but did reduce nighttime systolic BP by 4.7 mm Hg. All 24-hour BP values were reduced significantly in the 13 patients with OSA who used CPAP at least 4 hours per night. CONCLUSIONS: Losartan reduced BP in OSA, but the reductions were less than in no-OSA. Add-on CPAP therapy resulted in no significant changes in 24-hour BP measures except in patients using CPAP efficiently. Clinical trial registered with www.clinicaltrials.gov (NCT00701428).​

Effect of Positive Airway Pressure on Cardiovascular Outcomes in Coronary Artery Disease Patients with Nonsleepy Obstructive Sleep Apnea. The RICCADSA Randomized Controlled Trial.

RATIONALE: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), many of whom do not report daytime sleepiness. First-line treatment for symptomatic OSA is continuous positive airway pressure (CPAP), but its value in patients without daytime sleepiness is uncertain. OBJECTIVES: To determine the effects of CPAP on long-term adverse cardiovascular outcome risk in patients with CAD with nonsleepy OSA. METHODS: This single-center, prospective, randomized, controlled, open-label, blinded evaluation trial was conducted between December 2005 and November 2010. Consecutive patients with newly revascularized CAD and OSA (apnea-hypopnea index ≥15/h) without daytime sleepiness (Epworth Sleepiness Scale score <10) were randomized to auto-titrating CPAP (n = 122) or no positive airway pressure (n = 122). MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the first event of repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality. Median follow-up was 57 months. The incidence of the primary endpoint did not differ significantly in patients who did versus did not receive CPAP (18.1% vs. 22.1%; hazard ratio, 0.80; 95% confidence interval, 0.46-1.41; P = 0.449). Adjusted on-treatment analysis showed a significant cardiovascular risk reduction in those who used CPAP for ≥4 versus <4 hours per night or did not receive treatment (hazard ratio, 0.29; 95% confidence interval, 0.10-0.86; P = 0.026). CONCLUSIONS: Routine prescription of CPAP to patients with CAD with nonsleepy OSA did not significantly reduce long-term adverse cardiovascular outcomes in the intention-to-treat population. There was a significant reduction after adjustment for baseline comorbidities and compliance with the treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 00519597).

Larger right atrium than left atrium is associated with all-cause mortality in elderly patients with heart failure.

BACKGROUND: While left atrial (LA) enlargement is known as an early sign of left heart disease with prognostic implications in heart failure (HF), the importance of right atrial (RA) enlargement is less well studied, and the prognostic implications of interatrial size comparison are insufficiently understood. The aim of this study was to test the hypothesis that RA area larger than LA area in apical four-chamber view is associated with all-cause mortality in elderly patients with HF independent of left ventricular ejection fraction (LVEF). METHODS: Retrospectively, 289 patients above 65 years hospitalized for HF between April 2007 and April 2008, and who underwent an echocardiogram, were enrolled. All-cause mortality was registered during a follow-up of at least 56 months. Baseline parameters measured were RA area, LA area, LA volume, LVEF, left ventricular mass (LVM), tissue Doppler systolic velocity of right ventricular free wall (SmRV), presence of severe tricuspid regurgitation (TR), tricuspid gradient, central venous pressure, systolic pulmonary artery pressure, as well as some parameters of diastolic function. RESULTS: In univariate analysis RA larger than LA was associated with all-cause mortality (hazard ratio [HR] of 1.88, P<.001). The relation of RA larger than LA to all-cause mortality remained even after adjusting for age, heart rate, LVEF, atrial fibrillation, percutaneous coronary intervention, LVM index, LA volume index, SmRV, and the presence of severe TR (HR: 1.79, P=.04). CONCLUSION: RA larger than LA, independently of LVEF, is associated with all-cause mortality in elderly patients hospitalized due to HF.

Optimizing the Management of Heart Failure With Preserved Ejection Fraction in the Elderly by Targeting Comorbidities (OPTIMIZE-HFPEF).

AIMS: The pathophysiology of heart failure with preserved ejection fraction (HFPEF) is not fully understood. A recently proposed mechanism for HFPEF is that it is a systemic pro-inflammatory state induced by comorbidities, leading to microvascular endothelial dysfunction and subsequent cardiac remodeling and dysfunction. We hypothesize that targeting comorbidities will improve outcomes in elderly patients with HFPEF. Thus, the aim of this study is to determine whether the combination of systematic screening and optimal management of prespecified comorbidities associated with HFPEF improves outcomes. METHODS: This multicenter, prospective, randomized intervention trial uses an open procedure with blinded endpoint assessment. Patients with HFPEF aged >60 years (n = 360) will be randomized 1:1 to the usual care or intervention arm of the trial. When randomized to the intervention arm, all patients will be systematically screened and optimally treated for the most frequent cardiovascular, metabolic, respiratory, and renal comorbidities. The primary endpoint is a composite clinical score that classifies each randomized patient as improved or deteriorated based on objective and subjective data at a 24-month follow-up performed by a blinded endpoint committee. CONCLUSION: Rather than targeting cardiac dysfunction, our study aims to present evidence for a possible paradigm shift in the management of HFPEF. Our novel concept focuses on the management of comorbidities as predisposing factors in HFPEF.

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.

Risk of uterine rupture in multiparous women after induction of labor with prostaglandin: A national population-based cohort study.

OBJECTIVE: To assess whether, after induction of labor with prostaglandin, multiparous (≥2 para) women have an increased risk of uterine rupture compared with nulliparous or uniparous women. METHODS: This was a retrospective population-based cohort study including women who underwent induction with prostaglandin in all maternity wards in Sweden between May 1996 and December 2019 (n = 56 784). The study cohort was obtained by using data from the Swedish Medical Birth Register, which contains information from maternity and delivery records. The main outcome measure was uterine rupture. RESULTS: Overall, multiparous women induced with prostaglandin had an increased risk of uterine rupture compared with nulliparous women (adjusted odds ratio [OR], 3.33 [95% confidence interval (CI), 1.38-8.04]; P < 0.007). Multiparous women with no previous cesarean section (CS) induced with prostaglandin had more than three times higher risk of uterine rupture (crude OR, 3.55 [95% Cl, 1.48-8.53]; P = 0.005) compared with nulliparous women and four times higher risk compared with uniparous women (OR, 4.10 [95% CI, 1.12-15.00]; P < 0.033). Multiparous women with previous CS had a decreased risk of uterine rupture compared with uniparous women with one previous CS (crude OR, 0.41 [95% Cl, 0.21-0.78]; P = 0.007). CONCLUSION: Our study implies that multiparity in women with no previous CS is a risk factor for uterine rupture when induced with prostaglandin. This should be taken into consideration when deciding on the appropriate method of induction.