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.

Motives, frequency, predictors and outcomes of MRA discontinuation in a real-world heart failure population.

INTRODUCTION: Mineralocorticoid receptor antagonists (MRAs) reduce mortality and morbidity in patients with heart failure and reduced ejection fraction (HFrEF), but are largely underused. We evaluated the frequency, motives, predictors and outcomes of MRA discontinuation in a real-world heart failure population. METHODS AND RESULTS: This was a single-centre, retrospective cohort study where medical record-based data were collected on patients with HFrEF between 2010 and 2018. In the final analysis, 572 patients were included that comprised the continued MRA group (n=275) and the discontinued MRA group (n=297). Patients that discontinued MRA were older, had a higher comorbidity index and a lower index estimated glomerular filtration rate (eGFR). Predictors of MRA discontinuations were increased S-potassium, lower eGFR, lower systolic blood pressure, higher frequency of comorbidities and a higher left ventricular ejection fraction. The most common reason for MRA discontinuation was renal dysfunction (n=97, 33%) with 59% of these having an eGFR <30 mL/min/1.73m2, and elevated S-potassium (n=71, 24%) with 32% of these having an S-potassium >5.5 mmol/L. Discontinuation of MRA increased the adjusted risk of all-cause mortality (HR 1.48; 95% CI 1.07 to 2.05; p=0.019). CONCLUSIONS: Half of all patients with HFrEF initiated on MRA discontinued the treatment. A substantial number of patients discontinued MRA without meeting the guideline-recommended levels of eGFR and S-potassium where mild to moderate hyperkalaemia seems to be the most decisive predictor. Further, MRA discontinuation was associated with increased adjusted risk of all-cause mortality.

Mineralocorticoid receptor antagonists use in patients with heart failure and impaired renal function.

AIMS: Impaired renal function is a major contributor to the low proportion of mineralocorticoid receptor antagonist (MRA) treatment in patients with heart failure with reduced ejection fraction (HFrEF). Our aims were to investigate the impact of MRA treatment on all-cause mortality and worsening renal function (WRF) in patients with HFrEF and moderately impaired renal function. METHODS: Retrospective data between 2010-2018 on HFrEF patients from a single-centre hospital with estimated glomerular renal function (eGFR) < 60 ml/min/1.73 m2 were analysed. WRF was defined as a decline of by eGFR ≥ 20%. RESULTS: 416 patients were included, 131 patients on MRA and 285 without MRA, mean age was 77 years (SD ± 9) and 82 years (SD ± 9), respectively. Median follow-up was 2 years. 128 patients (32%) experienced WRF, 25% in the MRA group and 30% in patients without MRA (p = 0.293). In multivariable analysis, hospitalization for heart failure and systolic blood pressure were associated with WRF (p = 0.015 and p = <0.001), but not use of MRA (p = 0.421). MRA treatment had no impact on the risk of adjusted all-cause mortality (HR 0.93; 95% CI, 0.66-1.32 p = 0.685). WRF was associated with increased adjusted risk of all-cause mortality (HR 1.43; 95% CI, 1.07-1.89 p = 0.014). Use of MRA did not increase the adjusted overall risk of mortality even when experiencing WRF (HR 1.15; 95% CI, 0.81-1.63 p = 0.422). CONCLUSION: In this cohort of elderly HFrEF patients with moderately impaired renal function, MRA did not increase risk for WRF or all-cause mortality.

Diabetes status-related differences in risk factors and mediators of heart failure in the general population: results from the MORGAM/BiomarCaRE consortium.

BACKGROUND: The risk of heart failure among diabetic individuals is high, even under tight glycemic control. The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers. METHODS: In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure. RESULTS: Over a median follow-up of 13.8 years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49-2.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59-2.69]; non-diabetes: HR 1.85 [1.68-2.02]), BMI (diabetes: HR 1.30 [1.18-1.42]; non-diabetes: HR 1.40 [1.35-1.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55-2.75]; non-diabetes: HR 2.86 [2.50-3.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82-2.80]; non-diabetes: HR 2.97 [2.21-4.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19-1.34]; non-diabetes: HR 1.43 [1.39-1.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04-1.16]; non-diabetes: HR 1.13 [1.10-1.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03-1.24]; non-diabetes: HR 1.29 [1.25-1.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9-52.3] and indirect effects (effect share 56.9% [47.7-66.1]) mediated by obesity (BMI, 13.2% [10.3-16.2]), cardiac strain/volume overload (nT-proBNP, 8.4% [-0.7-17.4]), and hyperglycemia (glucose, 12.0% [4.2-19.9]). CONCLUSIONS: The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.

[Focus on individualized therapy for patients with acute coronary syndrome without persistent ST-segment elevation]. / Fokus på individuell behandling vid akut koronart syndrom utan ST-höjning.

New guidelines from the European Society of Cardiology (ESC) for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (NSTEMI-ACS) stress the importance of more individualized diagnostics and therapy based on the patients' initial risk profile balancing risk of ischemia with risk of bleeding. In this commentary, the Working Group on Coronary Artery Disease of the Swedish Society of Cardiology points out what is new in the 2020 NSTEMI guidelines.

A systematic approach for introduction of novel treatments to a chronic patient group: sacubitril-valsartan as a case study.

PURPOSE: To develop a model for systematic introduction and to test the feasibility in a chronic disease population. We also investigated how the approach was received by the patients. METHODS AND RESULTS: The systematic introduction approach is a seven-step procedure: step 1, define a few main criteria; step 2, primary scan patients with the one or two main criteria using computerized medical records/databases/clinical registries; step 3, identify patients applying the other predefined criteria; step 4, evaluate if any examinations/laboratory test updates are required; step 5, summon identified patients to the clinic with an information letter; step 6, discuss treatment with the patient and prescribe if appropriate; and step 7, follow up on initiated therapy and evaluate the applied process. The model was tested in a case study during introduction of the new drug sacubitril-valsartan in a heart failure population. In total, 76 out of 1924 patients were identified to be eligible for sacubitril-valsartan and summoned to the clinic to discuss treatment. Patient experiences with the approach were investigated in an interview study with general inductive approach using qualitative content analysis. This resulted in three final categories: a good approach, role of the information letter, and trust in care. CONCLUSIONS: The systematic introduction approach ensures that strict criteria are used in the selection process and that a treatment can be implemented in eligible patients within a specified population with limited resources and time. The model was effective in our case study and maintained the patient's confidence in healthcare.

Comparison of creatinine-based methods for estimating glomerular filtration rate in patients with heart failure.

AIMS: Glomerular filtration rate is an important factor in management of heart failure (HF). Our objective was to validate eight creatinine-based equations for estimating glomerular filtration rate (eGFR) in an HF population against measured glomerular filtration rate. METHODS AND RESULTS: One hundred forty-six HF patients (mean age 68 ± 13 years, mean left ventricular ejection fraction 45% ± 15) within a single-centre hospital that underwent 51 Cr-EDTA clearance between 2010 and 2018 were included in this retrospective study. eGFR was estimated by means of Cockcroft-Gault ideal and actual weight, the Modification of Diet in Renal Disease Study (MDRD), simplified MDRD with isotope dilution mass spectroscopy traceable calibration, the Chronic Kidney Disease Epidemiology Collaboration, revised Lund-Malmö, full age spectrum, and the Berlin Initiative Study 1. Mean measured glomerular filtration rate was 42 mL/min/1.73 m2 . Pearson's correlation coefficient (r) had the highest precision for MDRD (r = 0.9), followed by revised Lund-Malmö (r = 0.88). All equations except MDRD (mean difference -4.8%) resulted in an overestimation of the renal function. The accuracy was below 75% for all equations except MDRD. CONCLUSIONS: None of the exclusively creatinine-based methods was accurate in predicting eGFR in HF patients. Our findings suggest that more accurate methods are needed for determining eGFR in patients with HF.

Differences in medical treatment and clinical characteristics between men and women with heart failure - a single-centre multivariable analysis.

PURPOSE: The aims of this study were to examine sex differences in a heart failure population with regards to treatment and patient characteristics and to investigate the impact of sex on achieved doses of heart failure medications. METHODS AND RESULTS: A total of 1924 patients with heart failure in a regional hospital were analysed, 622 patients had ejection fraction ≤ 40% of which 30% were women. In patients with reduced ejection fraction, women were older (79 ± 11 vs. 74 ± 12 years, P < 0.001), had lower body weight (70 ± 17 vs. 86 ± 18 kg, P < 0.001), lower estimated glomerular filtration rate (eGFR) (49 ± 24 vs. 71 ± 30 ml/min, P < 0.001) and received lower doses of heart failure medications than men. Multivariable linear regression on patients with reduced ejection fraction showed that sex was not associated with achieved dose of any heart failure medication. For angiotensin-converting enzyme inhibitors and angiotensin receptor blockers associated factors were eGFR, systolic blood pressure, age, ejection fraction, and heart rate. For beta-blockers associated factors were body weight, atrial fibrillation and age. For mineralocorticoid receptor antagonists associated factors were eGFR, serum potassium, age, systolic blood pressure, ejection fraction and heart rate. CONCLUSION: Women with heart failure and reduced ejection fraction were prescribed lower doses of heart failure medications, were older, had worse renal function, and lower body weight than men. Sex was not independently associated with achieved doses of heart failure medications, instead age, renal function and body weight explained the differences in treatment.

Safety and Tolerability of Initiating Maximum-Dose Sacubitril-Valsartan in Patients on Target Dose Renin-Angiotensin System Inhibitors.

AIM: Sacubitril-valsartan has proven beneficial in heart failure with reduced ejection fraction. Guidelines recommend initiating half-dose sacubitril-valsartan before up-titration even to patients already on target dose angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). To reduce the number of titration steps needed in order to simplify for the patient as well as the clinic, we aimed to investigate the safety and tolerability of switching patients on target dose ACE inhibitors or ARBs directly to maximum-dose sacubitril-valsartan. METHODS: This prospective cohort study was conducted between April 2016 and November 2017. A total of 66 patients with heart failure and reduced ejection fraction already on guideline-recommended target dose ACE inhibitors or ARBs (equivalent to enalapril 10 mg twice daily) were switched to maximum-dose sacubitril-valsartan (200 mg twice daily). The patients were followed for twelve months. RESULTS: Patients had a mean age of 72 ± 10 years, mean systolic blood pressure of 121 ± 17 mmHg, and 92% were male. At 12-month follow-up, nine patients (14%) had discontinued sacubitril-valsartan, four patients (6%) had a dose reduction, and 17 patients (26%) had developed symptomatic hypotension. No angioedema occurred within the 12-month follow-up and there were no hospitalizations or emergency room visits within the first 14 days. CONCLUSIONS: Switching directly from target dose ACE inhibitors or ARBs to maximum-dose sacubitril-valsartan was safe and generally well tolerated.

Obstacles to mineralocorticoid receptor antagonists in a community-based heart failure population.

AIM: Previous studies and national assessments indicate an undertreatment of mineralocorticoid receptor antagonists (MRA) in heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate why MRA is not used to full extent. METHODS: A complete community-based heart failure population was studied. Several variables were collected, and medical records were scrutinized to identify reasons for not prescribing MRA. RESULTS: Of 2029 patients, 812 had EF ≤40%. Five hundred and fifty-three patients (68%) tried MRA at some point but 184 of these (33%) discontinued therapy. There were 259 patients that never tried MRA with 177 with a listed explanation or contraindication. Eighty-two patients, 10% of the total HFrEF population, had no clear contraindications. They were older and had less HF hospitalizations compared to patients on MRA (P < 0.05) and 32% did not have any follow-up at the cardiology clinic. Contraindications to MRA were renal dysfunction (93 patients), hypotension (28 patients), and hyperkalemia (25 patients). Only six patients had hyperkalemia without renal dysfunction. Of the patients with renal dysfunction, 66 (72%) had eGFR >30 mL/min. CONCLUSIONS: The reasons why MRA are underutilized were mainly because of contraindications. However, the data suggest that physicians are overly cautious about moderately reduced kidney function. There seems to be a 10%-18% avoidable undertreatment with MRA, especially for elderly patients that are admitted to the hospital for other reasons than heart failure. This suggests that patients with heart failure would benefit from routine follow-up at a cardiology clinic.

[ST-elevation myocardial infarction and dual antiplatelet therapy: new guidelines]. / ST-höjningsinfarkt och dubbel trombocythämning: nya riktlinjer - Europeiska kardiologföreningens rekommendationer kommenteras av Svenska kardiologföreningens arbetsgrupp.

This report summarizes some of the most important changes and new recommendations from the ESC ST-elevation myocardial infarction and double antiplatelet therapy guidelines for 2017, which are of interest for physicians managing patients with coronary artery disease.

Eligibility of sacubitril-valsartan in a real-world heart failure population: a community-based single-centre study.

AIMS: This study aims to investigate the eligibility of the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor (ARNI) with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study to a real-world heart failure population. METHODS AND RESULTS: Medical records of all heart failure patients living within the catchment area of Umeå University Hospital were reviewed. This district consists of around 150 000 people. Out of 2029 patients with a diagnosis of heart failure, 1924 (95%) had at least one echocardiography performed, and 401 patients had an ejection fraction of ≤35% at their latest examination. The major PARADIGM-HF criteria were applied, and 95 patients fulfilled all enrolment criteria and thus were eligible for sacubitril-valsartan. This corresponds to 5% of the overall heart failure population and 24% of the population with ejection fraction ≤ 35%. The eligible patients were significantly older (73.2 ± 10.3 vs. 63.8 ± 11.5 years), had higher blood pressure (128 ± 17 vs. 122 ± 15 mmHg), had higher heart rate (77 ± 17 vs. 72 ± 12 b.p.m.), and had more atrial fibrillation (51.6% vs. 36.2%) than did the PARADIGM-HF population. CONCLUSIONS: Only 24% of our real-world heart failure and reduced ejection fraction population was eligible for sacubitril-valsartan, and the real-world heart failure and reduced ejection fraction patients were significantly older than the PARADIGM-HF population. The lack of data on a majority of the patients that we see in clinical practice is a real problem, and we are limited to extrapolation of results on a slightly different population. This is difficult to address, but perhaps registry-based randomized clinical trials will help to solve this issue.

Depression among the very old with dementia.

OBJECTIVES: The aim of this study was to investigate the prevalence of depression among very old individuals with dementia compared to those without dementia and to examine if there were any differences regarding associated factors between people with or without depression in these conditions. METHODS: In a population-based study in Sweden, 363 participants aged 85 years and above, were evaluated for depression and dementia. RESULTS: The prevalence of depression was significantly higher among the people with dementia than without dementia, 43% vs. 24% (p < 0.001). Approximately 2/3 of the depressed in both groups used antidepressants and of those, approximately 50% had responded. Depression in the group without dementia was, among other factors, associated with higher total number of medication, the use of significant more analgesics and benzodiazepines, loneliness, inability of going outside and recent loss of child. The loss of a child was the only factor that was independently associated with depression in those with dementia. CONCLUSIONS: The present study confirms that in the very old, depression is more common among people with dementia than without dementia. A large proportion, both with and without dementia, are under-diagnosed and untreated, and in addition many subjects in both groups studied were non-responders to treatment. Many of the factors associated with depression among people without dementia in this study were not associated with depression among those with dementia, thus supporting the theory that the spectrum of associated factors for depression in dementia seems to be different from that for depression in people without dementia.

One-week prevalence of depressive symptoms and psychotropic drug treatments among old people with different levels of cognitive impairment living in institutional care: changes between 1982 and 2000.

BACKGROUND: Dementia and depression are common in advanced age, and often co-exist. There are indications of a decreased prevalence of depressive symptoms among old people in recent years, supposedly because of the manifold increase in antidepressant treatment. Whether the prevalence of depressive symptoms has decreased among people in different stages of dementia disorders has not yet been investigated. METHODS: A comparison was undertaken of two cross-sectional studies, conducted in 1982 and 2000, comprising 6864 participants living in geriatric care units in the county of Västerbotten, Sweden. Depressive symptoms were measured using the Multi-Dimensional Dementia Assessment Scale (MDDAS), and the cognitive score was measured with Gottfries' cognitive scale. Drug data were obtained from prescription records. RESULTS: There was a significant decrease in depressive symptom score between 1982 and 2000 in all cognitive function groups except for the group with moderate cognitive impairment. Antidepressant drug use increased in all cognitive function groups. CONCLUSION: The prevalence of depressive symptoms decreased between 1982 and 2000, in all levels of cognitive impairment except moderate cognitive impairment. This might possibly be explained by the depressive symptoms having different etiologies in different stages of a dementia disorder, which in turn might not be equally susceptible to antidepressant treatment.

Gender differences in depression among the very old.

OBJECTIVES: The aim of this study was to investigate factors associated with depression among men and women aged 85 and over. METHOD: A population-based study was undertaken in northern Sweden. Out of 527 eligible participants, aged 85, 90 or > or = 95, 363 were evaluated for depression. Data were collected from structured interviews, assessments and medical charts and from relatives and caregivers. Depression was screened for using the Geriatric Depression Scale-15 and further assessed using the Montgomerysberg Depression Rating Scale (MADRS). RESULTS: A higher proportion of women were diagnosed with depression (33% vs. 18.6%, p = 0.006). In both men and women experienced loneliness (OR 3.4 vs. 7.0) and not going outside independently (OR 2.6 vs. 26.0) were associated with depression in the final regression model. Depression among men was also independently associated with loss of a child/children during the preceeding ten years (OR 30.0). CONCLUSION: Depression was more common among women than among men. Experienced loneliness and not going outside independently seem to be closely related to depression in both men and women. Loss of a child seems to be the most important factor among men.

Depression among the oldest old: the Umeå 85+ study.

OBJECTIVES: To investigate the prevalence of depression among the oldest old and to analyze factors associated with depression. METHODS: A cross-sectional, population-based study was undertaken in Umeå, Sweden. Out of 319 eligible participants aged 85, 90 and 95 years and older, it was possible to evaluate 242 people (75.9%) for depression. Data were collected from structured interviews and assessments in the participants' homes, and from medical charts, relatives and caregivers. Depression was screened for using the Geriatric Depression Scale-15 and further assessed with the Montgomery-Asberg Depression Rating Scale. Cognition was assessed using the Mini-mental State Examination, activities of daily living (ADL) using the Barthel ADL Index, nutrition using the Mini Nutritional Assessment and well-being using the Philadelphia Geriatric Center Morale Scale. RESULTS: The 85-year-olds had a significantly lower prevalence of depression than the 90- and 95-year-olds (16.8% vs. 34.1% and 32.3%). No sex differences were found. One-third of those with depression had no treatment and among those with ongoing treatment 59% were still depressed. Persons diagnosed with depression had a poorer well-being and a higher 1-year mortality. Logistic regression analyses showed that depression was independently associated with living in institutions and number of medications. CONCLUSION: Depression among the oldest old is common, underdiagnosed and inadequately treated, and causes poor well-being and increased mortality. More knowledge about depression is essential to improve the assessment and treatment of depression among the oldest old.