Does iodine fortification affect the risk of atrial fibrillation in incident hyperthyroidism? A national register-based cohort.

OBJECTIVE: Iodine fortification (IF) induces an initial increase followed by a decrease in the incidence of hyperthyroidism in the general population. Within the population of hyperthyroid patients, the sex-, age- and subtype distribution changes after IF. The risk of atrial fibrillation (AF) in hyperthyroid patients may be influenced by these factors. Therefore, we aimed to examine how the association between incident hyperthyroidism and AF was affected by IF increasing the population iodine intake from moderate-mild iodine deficiency to low adequacy. DESIGN, PATIENTS AND MEASUREMENTS: Incident hyperthyroid patients were included at the date of first inpatient or outpatient diagnosis, and AF diagnoses within 3 months before to 6 months after the index date were identified in Danish nationwide registers, 1997-2018. The relative risk (RR) of AF each calendar year (reference: 1997; IF introduced: 2000) was analyzed in Poisson regression models adjusted for age, sex, educational level, geographic region, and comorbidities. RESULTS: Overall, in 62,201 patients with incident hyperthyroidism 7.9% were diagnosed with AF. There was a minor nonsignificantly increased risk of AF during the first years after IF followed by a gradual decrease to RR 0.76 (0.62-0.94) in 2017. There were no statistically significant differences in the development in the risk of AF by sex, age group, or geographic region. CONCLUSIONS: Results indicate that IF may reduce the risk of concomitant AF in hyperthyroid patients. If these results are confirmed, IF may not only reduce the population incidence of hyperthyroidism but also reduce the burden of morbidity in the remaining hyperthyroid patients.

[15O]H2O myocardial perfusion positron emission tomography: Added value of relative stress perfusion deficit in the prediction of significant coronary artery stenosis in a mixedpopulation.

BACKGROUND: It remains unknown whether estimation of the relative stress perfusion deficit offers added value in the prediction of significant coronary artery stenosis in myocardial perfusion imaging with [15O]H2O positron emission tomography (PET) in a population with high prevalence of established cardiac disease. METHODS: During eight months, we consecutively included all patients undergoing [15O]H2O PET and subsequent invasive coronary angiography (ICA). Significant stenosis was defined from ICA as fractional flow reserve ≤.8 or coronary artery narrowing of ≥70%. We calculated absolute and relative total perfusion deficits (aTPD and rTPD, respectively) as semiquantitative measures of the extent and severity of reduced stress perfusion. A multivariate logistic regression analysis was performed to test the adjusted associations (odds ratio (OR) with 95% CI) with significant coronary artery stenosis. RESULTS: Of 800 patients undergoing [15O]H2O PET, 144 underwent ICA, where 142 patients had aTPD of ≥3% and 79 (55%) of these had at least one significant stenosis. In an adjusted analysis, rTPD (OR10% increase = 2.12 (1.44-3.12), P < .001), previous coronary artery bypass grafting (CABG) (OR = .11 (.03-.36), P < .001) and reduced left ventricular ejection fraction (LVEF) (OR = .25 (.08-.84), P = .02) were independently associated with significant stenosis, whereas the association with aTPD (OR10% increase = 1.14 (.98-1.32), P = .08) was modest. CONCLUSIONS: In the presence of an absolute perfusion deficit (aTPD of ≥3%), rTPD may improve the prediction of significant stenosis in a heterogeneous population of patients examined with [15O]H2O PET. Furthermore, previous CABG and reduced LVEF are associated with nonstenotic perfusion deficiencies, suggesting caution when interpreting myocardial perfusion imaging in such patients.

Cardiovascular events according to blood pressure thresholds recommended by ACC/AHA.

AIM: The latest guidelines from ACC/AHA define hypertension at systolic blood pressure (SBP) 130-139 mmHg or diastolic blood pressure (DBP) 80-89 mmHg in contrast to guidelines from ESC/ESH defining hypertension at SBP ≥ 140 mmHg or DBP ≥ 90 mmHg. The aim was to determine whether the ACC/AHA definition of hypertension identifies persons at elevated risk for future cardiovascular outcome. METHODS: In a Danish prospective cardiovascular study, 19,721 white men and women aged 20-98 years were examined up to five occasions between 1976 and 2015. The population was followed until December 2018. The ACC/AHA definition of the BP levels were applied: Normal: SBP <120 mmHg and DBP <80 mmHg, Elevated: SBP 120-129 mmHg and DBP <80 mmHg, Stage 1: SBP 130-139 mmHg or DBP 80-89 mmHg, Stage 2: SBP ≥140 mmHg or DBP ≥90 mmHg. Absolute 10-year risk was calculated taking repeated examinations, covariates, and competing risk into account. RESULTS: For all outcomes, the 10-year risk in stage 1 hypertension did not differ significantly from risk in subjects with normal BP: The 10-year risk of cardiovascular events in stage 1 hypertension was 14.1% [95% CI 13.2;15.0] and did not differ significantly from the risk in normal BP at 12.8% [95% CI 11.1;14.5] (p = 0.19). The risk was highest in stage 2 hypertension 19.4% [95% CI 18.9;20.0] and differed significantly from normal BP, elevated BP, and stage 1 hypertension (p < 0.001). The 10-year risk of cardiovascular death was 6.6% [95% CI 5.9;7.4] in stage 1 hypertension and did not differ significantly from the risk in normal BP at 5.7% [95% CI 4.1;7.3] (p = 0.33). CONCLUSIONS: Stage 1 hypertension as defined by the ACC/AHA guidelines has the same risk for future cardiovascular events as normal BP. In contrast, the definition of hypertension as suggested by ESC/ESH identifies patients with elevated risk of cardiovascular events.

Until 2017, there was worldwide agreement on defining hypertension at systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg.In 2017, the American Cardiology Societies (ACC and AHA) lowered the threshold for defining hypertension at SBP 130-139 mmHg or DBP 80-89 mmHg.Lowering the threshold might make healthy persons sick if the thresholds do not identify persons at high risk.Unnecessary medical treatment is associated with high economic cost for the health care systems.We wanted to explore whether applying the American BP definition in a Scandinavian population identified persons with elevated risk for cardiovascular disease.As part of the Copenhagen City Heart study, 19,721 men and women aged 20-98 years were followed from 1976.They went through up to five examinations between 1976 and 2018 including BP measurements.We applied the American BP thresholds and followed the persons until death or 2018.In Denmark all citizens have a unique identification number which is linked to all health care contacts and administrative registers.We used advanced statistical methods and linked the BP measurements with the data for cardiovascular disease and death date from the Danish registries for each person.The results showed that the American definition of hypertension has same risk for future cardiovascular disease as the definition of normal BP.This means that healthy persons will be diagnosed with hypertension if the US guidelines were applied in Denmark.

Prevalence and management of familial hypercholesterolaemia in patients with chest pain admitted to hospital: a retrospective observational study.

OBJECTIVES: Patients with familial hypercholesterolaemia (FH) are genetically burdened by a lifelong elevation of the low-density lipoprotein cholesterol (LDL-C) level, putting them at a very high risk of premature ischaemic heart disease (IHD). This study aims to assess the prevalence of FH among patients admitted for IHD and the preventive treatment status before admission. DESIGN: Observational, retrospective, register-based study. SETTING: Individuals discharged with a diagnosis of IHD were enrolled consecutively throughout 2012-2016 from the cardiac care units of two hospitals in Copenhagen. PARTICIPANTS: 4223 individuals were discharged during the period. Inclusion criteria for further investigation were the availability of one measurement of LDL-C at the time of admission. In total, 2797 individuals were included for further investigation. There were no exclusion criteria. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary objective has been to determine the prevalence of FH in the population. The secondary objective has been to determine the use of lipid-lowering therapy and to which extend the individuals reach their treatment goal. RESULTS: Among the 2797 consecutive patients evaluated, the prevalence of potential FH was 7.7% (1: 13) and 6.8% (1:15) had probably or definite FH. The prevalence of FH was age-dependent: Among the 680 patients (24.3%) with premature IHD (men <55 years/women <60 years), 136 patients (20.0%) had potential FH and 21 (3.1%) had probable/definite FH. None were diagnosed and almost none attained their treatment goal. CONCLUSIONS: There is still a massive lack of recognition of FH in patients admitted to a cardiac care unit with a diagnosis of IHD. Despite a measured high LDL-C, the diagnosis was not made for any patients not even in patients who were admitted at an early age or had a previous cardiovascular event.

Contact with general practice in patients with suspected chronic coronary syndrome before and after CT angiography compared with the general population.

BACKGROUND: Most patients undergoing coronary computed tomography angiography (CCTA) to diagnose coronary artery disease (CAD) are referred from general practitioners (GP). The burden in contacts to GP in relation to investigation on suspected CAD is unknown. METHODS: All patients undergoing CCTA in Western Denmark from 2014-2022 were included. CCTA stenosis was defined as diameter stenosis of ≥ 50%. Patients with and without stenosis were matched, in each group, 1:5 to a reference population based on birth-year, gender and municipality using data from national registries. All GP visits were registered in up to five years preceding and one year after the CTA and stratified by gender and age. Charlson comorbidity index (CCI) were calculated in all groups. RESULTS: Of the 62 512 patients included, 12 886 had a stenosis while 49 626 did not. Patients in both groups had a substantially higher GP visit frequency compared to reference populations. In the year of coronary CTA median GP contacts in patients with stenosis was 11 [6-17] vs. 6 [2-11] in the reference population (P < 0.001), in patients without stenosis 10 [6-17] vs. 5 [2-11] (P < 0.001). These findings were consistent across age and gender. CCI was higher among both patients with and without stenosis compared to reference groups. CONCLUSION: In patients undergoing CCTA to diagnose CAD, a substantially increased frequency of contacts to GP was observed in the five-year period prior to examination compared to the reference populations regardless of the CCTA findings. Obtaining the CCTA result did not seem to substantially affect the GP visit frequency.

Long-term aspirin adherence following myocardial infarction and risk of cardiovascular events.

BACKGROUND AND AIMS: Aspirin is considered mandatory after myocardial infarction (MI). However, its long-term efficacy has been questioned. This study investigated the effectiveness of long-term aspirin after MI. METHODS: Patients ≥ 40 years with MI from 2004-2017 who were adherent to aspirin one year after MI were included from Danish nationwide registries. At 2, 4, 6, and 8 years after MI, continued adherence to aspirin was evaluated. Absolute and relative risks of MI, stroke, or death at 2 years from each timepoint were calculated using multivariable logistic regression analysis with average treatment effect modeling standardized for age, sex, and comorbidities. Subgroup analyses were stratified by sex and age > and ≤ 65 years. RESULTS: Among 40 114 individuals included, the risk of the composite endpoint was significantly higher for nonadherent patients at all timepoints. The absolute risk was highest at 2-4 years after MI for both adherent (8.34%, 95% confidence interval [CI]: 8.05-8.64%) and nonadherent patients (10.72%, 95% CI: 9.78-11.66%). The relative risk associated with nonadherence decreased from 4 years after index-MI and onwards: 1.41 (95% CI: 1.27-1.55) at 4-6 years and 1.21 (95% CI: 1.06-1.36) at 8-10 years (Ptrend = 0.056). Aspirin nonadherence in women and individuals > 65 years was not associated with increased risk. Pinteraction at each of the timepoints: Age-<0.001, <0.001, 0.002, 0.51; Sex - 0.25, 0.02, 0.02, 0.82. CONCLUSION: Nonadherence to long-term aspirin was associated with increased risk of MI, stroke, or death, but not in women or individuals > 65 years. The risk decreased from 4 years after MI with near statistical significance.

Exercise training and high-sensitivity cardiac troponin-I in patients with heart failure with reduced ejection fraction.

AIMS: The aims of this sub-study of the SMARTEX trial were (1) to evaluate the effects of a 12-week exercise training programme on serum levels of high sensitivity cardiac troponin I (hs-cTnI) in patients with moderate chronic heart failure (CHF), in New York Heart Association class II-III with reduced ejection fraction (HFrEF) and (2) to explore the associations with left ventricular remodelling, functional capacity and filling pressures measured with N-terminal pro brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: In this sub-study, 196 patients were randomly assigned to high intensity interval training (HIIT, n = 70), moderate continuous training (MCT, n = 59) or recommendation of regular exercise (RRE), (n = 67) for 12 weeks. To reveal potential difference between structured intervention and control, HIIT and MCT groups were merged and named supervised exercise training (SET) group. The RRE group constituted the control group (CG). To avoid contributing factors to myocardial injury, we also evaluated changes in patients without additional co-morbidities (atrial fibrillation, hypertension, diabetes mellitus, and chronic obstructive pulmonary disease). The relationship between hs-cTnI and left ventricular end-diastolic diameter (LVEDD), VO2peak, and NT-proBNP was analysed by linear mixed models. At 12 weeks, Hs-cTnI levels were modestly but significantly reduced in the SET group from median 11.9 ng/L (interquartile ratio, IQR 7.1-21.8) to 11.5 ng/L (IQR 7.0-20.7), P = 0.030. There was no between-group difference (SET vs. CG, P = 0.116). There was a numerical but not significant reduction in hs-cTnI for the whole population (P = 0.067) after 12 weeks. For the sub-group of patients without additional co-morbidities, there was a significant between-group difference: SET group (delta -1.2 ng/L, IQR -2.7 to 0.1) versus CG (delta -0.1 ng/L, IQR -0.4 to 0.7), P = 0.007. In the SET group, hs-cTnI changed from 10.9 ng/L (IQR 6.0-22.7) to 9.2 ng/L (IQR 5.2-20.5) (P = 0.002), whereas there was no change in the CG (6.4 to 5.8 ng/L, P = 0.64). Changes in hs-cTnI (all patients) were significantly associated with changes in; LVEDD, VO2peak, and NT-proBNP, respectively. CONCLUSIONS: In patients with stable HFrEF, 12 weeks of structured exercise intervention was associated with a modest, but significant reduction of hs-cTnI. There was no significant difference between intervention group and control group. In the sub-group of patients without additional co-morbidities, this difference was highly significant. The alterations in hs-cTnI were associated with reduction of LVEDD and natriuretic peptide concentrations as well as improved functional capacity.

Health-related quality of life in elderly cardiac patients undergoing cardiac rehabilitation and the association with exercise capacity: The EU-CaRE study.

AIMS: The ability to be physically active is pivotal to the quality of life in elderly patients. This study aims to describe the association between exercise capacity and health-related quality of life (HRQoL), anxiety, and depression following an exercise-based cardiac rehabilitation (CR) program in elderly cardiac patients. METHODS: Patients aged ≥65 years with acute and chronic coronary syndrome or heart valve surgery were consecutively included from 8 CR centers in 7 European countries. Exercise capacity (VO2peak(ml/kg/min)) was assessed with a cardiopulmonary exercise test (97%) or a six-minute walk test. Outcome variables included HRQoL (SF-36 physical and mental component scores (PCS and MCS)), anxiety (GAD-7), and depression (PHQ-9). Mixed models were used to address the association between baseline and the development in VO2peak, and outcome variables stratified on sex, and adjusted for baseline values, age, and CR center. RESULTS: A total of 1,633 patients were included (T0), 1,523 (93%) completed end-of-CR assessment (T1), and 1,457 (89%) 1-year follow-up (T2). Women had higher % of predicted VO2peak, but poorer scores in HRQoL, anxiety and depression at all time-points. All scores improved in both sexes at follow-up. We found significant associations between VO2peak at baseline as well as development in VO2peak and all outcome variables at T1 and T2 in men (all p < 0.001). In women, VO2peak was only associated with PCS scores (p < 0.001). CONCLUSIONS: Improvements in exercise capacity was strongly associated with improvements in HRQoL and mental health, however with stronger associations in men. The results highlight the importance of physical fitness for HRQol and mental health. The findings from this study might be useful to better target individual CR programs.

This study explores the association between exercise capacity and the well-being of elderly cardiac patients participating in a cardiac rehabilitation program, focusing on health-related quality of life (HRQoL), anxiety, and depression. Key Findings:Women, despite having higher percentages of predicted exercise capacity, consistently reported poorer HRQoL, anxiety, and depression scores compared to men at all assessed time points.Improvements in exercise capacity were strongly associated with positive changes in HRQoL and mental health, with these associations being more pronounced in men.

Hemodynamic Response in Ascending Aorta Surgery Patients during Moderate Intensity Resistance Training.

Background: In patients undergoing ascending aortic surgery (AAS), postsurgical physical exercise with a safe and effective exercise prescription is recommended. Resistance training is associated with blood pressure (BP) elevations that may increase the risk of new aortic dissection or rupture. However, the acute hemodynamic response to resistance training for this patient group is unknown. Aim: The aim of this study was to investigate peak systolic BP (SBP) increases in AAS patients during moderate intensity resistance training. Methods: SBP was measured continuously beat-to-beat with a noninvasive method during three sets of leg presses at moderate intensity. A 15-repetition maximum strength test was performed to estimate the maximal amount of resistance a participant could manage 15 times consecutively (equivalent to approximately 60-65% of their maximum strength). Results: The study had 48 participants in total, i.e., 24 cases and 24 controls. Both groups consisted of 10 females (42%) and 14 males (58%). The case group had a mean age of 60.0 (SD ± 11.9) years and a mean of 16.3 months since surgery (minimum 4.4 and maximum 39.6 months). 22 of the 24 cases received antihypertensive medication. The median baseline BP was 119/74 mmHg among cases and 120/73 mmHg among controls. During the first set of leg presses, the median peak SBP was 152 mmHg, in the second set 154 mmHg, and in the third set 165 mmHg. Corresponding values in controls were 170 mmHg, 181 mmHg, and 179 mmHg. The highest peak SBP registered in an AAS patient was 190 mmHg and in any healthy control was 287 mmHg. Conclusion: The findings indicate that AAS patients in control of their BP have the endurance to perform 3 sets of resistance training at moderate intensity as their SBP increases with a maximum of 39% from the baseline compared to the 51% increase in the control group.

Biomarkers and Coronary Microvascular Dysfunction in Women With Angina and No Obstructive Coronary Artery Disease.

Background: Coronary microvascular dysfunction (CMD) is a major cause of ischemia with no obstructed coronary arteries. Objectives: The authors sought to assess protein biomarker signature for CMD. Methods: We quantified 184 unique cardiovascular proteins with proximity extension assay in 1,471 women with angina and no obstructive coronary artery disease characterized for CMD by coronary flow velocity reserve (CFVR) by transthoracic echo Doppler. We performed Pearson's correlations of CFVR and each of the 184 biomarkers, and principal component analyses and weighted correlation network analysis to identify clusters linked to CMD. For prediction of CMD (CFVR < 2.25), we applied logistic regression and machine learning algorithms (least absolute shrinkage and selection operator, random forest, extreme gradient boosting, and adaptive boosting) in discovery and validation cohorts. Results: Sixty-one biomarkers were correlated with CFVR with strongest correlations for renin (REN), growth differentiation factor 15, brain natriuretic protein (BNP), N-terminal-proBNP (NT-proBNP), and adrenomedullin (ADM) (all P < 1e-06). Two principal components with highest loading on BNP/NTproBNP and interleukin 6, respectively, were strongly associated with low CFVR. Weighted correlation network analysis identified 2 clusters associated with low CFVR reflecting involvement of hypertension/vascular function and immune modulation. The best prediction model for CFVR <2.25 using clinical data had area under the receiver operating characteristic curve (ROC-AUC) of 0.61 (95% CI: 0.56-0.66). ROC-AUC was 0.66 (95% CI: 0.62-0.71) with addition of biomarkers (P for model improvement = 0.01). Stringent two-layer cross-validated machine learning models had ROC-AUC ranging from 0.58 to 0.66; the most predictive biomarkers were REN, BNP, NT-proBNP, growth differentiation factor 15, and ADM. Conclusions: CMD was associated with pathways particularly involving inflammation (interleukin 6), blood pressure (REN, ADM), and ventricular remodeling (BNP/NT-proBNP) independently of clinical risk factors. Model prediction improved with biomarkers, but prediction remained moderate.

Moderate continuous or high intensity interval exercise in heart failure with reduced ejection fraction: Differences between ischemic and non-ischemic etiology.

Background: Exercise for heart failure (HF) with reduced ejection fraction (HFrEF) is recommended by guidelines, but exercise mode and intensities are not differentiated between HF etiologies. We, therefore, investigated the effect of moderate or high intensity exercise on left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and maximal exercise capacity (peak VO2) in patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM). Methods: The Study of Myocardial Recovery after Exercise Training in Heart Failure (SMARTEX-HF) consecutively enrolled 231 patients with HFrEF (LVEF ≤ 35 %, NYHA II-III) in a 12-weeks supervised exercise program. Patients were stratified for HFrEF etiology (ICM versus NICM) and randomly assigned (1:1:1) to supervised exercise thrice weekly: a) moderate continuous training (MCT) at 60-70 % of peak heart rate (HR), b) high intensity interval training (HIIIT) at 90-95 % peak HR, or c) recommendation of regular exercise (RRE) according to guidelines. LVEDD, LVEF and peak VO2 were assessed at baseline, after 12 and 52 weeks. Results: 215 patients completed the intervention. ICM (59 %; n = 126) compared to NICM patients (41 %; n = 89) had significantly lower peak VO2 values at baseline and after 12 weeks (difference in peak VO2 2.2 mL/(kg*min); p < 0.0005) without differences between time points (p = 0.11) or training groups (p = 0.15). Etiology did not influence changes of LVEDD or LVEF (p = 0.30; p = 0.12), even when adjusting for sex, age and smoking status (p = 0.54; p = 0.12). Similar findings were observed after 52 weeks. Conclusions: Etiology of HFrEF did not influence the effects of moderate or high intensity exercise on cardiac dimensions, systolic function or exercise capacity. Clinical Trial Registration­URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.