Transcription Factor Regulation of Gene Expression Network by ZNF385D and HAND2 in Carotid Atherosclerosis.

Carotid intima-media thickness (CIMT) is a surrogate indicator for atherosclerosis and has been shown to predict cardiovascular risk in multiple large studies. Identification of molecular markers for carotid atheroma plaque formation can be critical for early intervention and prevention of atherosclerosis. This study performed transcription factor (TF) network analysis of global gene expression data focusing on two TF genes, ZNF385D and HAND2, whose polymorphisms have been recently reported to show association with CIMT. Genome-wide gene expression data were measured from pieces of carotid endarterectomy collected from 34 hypertensive patients (atheroma plaque of stages IV and above according to the Stary classification) each paired with one sample of distant macroscopically intact tissue (stages I and II). Transcriptional regulation networks or the regulons were reconstructed for ZNF385D (5644 target genes) and HAND2 (781 target genes) using network inference. Their association with the progression of carotid atheroma was examined using gene-set enrichment analysis with extremely high statistical significance for regulons of both ZNF385D and HAND2 (p < 6.95 × 10-7) suggesting the involvement of expression quantitative loci (eQTL). Functional annotation of the regulon genes found heavy involvement in the immune system's response to inflammation and infection in the development of atherosclerosis. Detailed examination of the regulation and correlation patterns suggests that activities of the two TF genes could have high clinical and interventional impacts on impairing carotid atheroma plaque formation and preventing carotid atherosclerosis.

15 weeks of soccer training increases left ventricular mass and improves indices of left ventricular diastolic function in previously sedentary, mildly hypertensive, middle-aged women.

PURPOSE: To investigate the impact of soccer training on cardiac adaptations in mildly hypertensive middle-aged women. METHODS: Hypertensive premenopausal women (n = 41; age (mean ± SD): 44 ± 7 years; height: 166 ± 6 cm; weight: 78.6 ± 11.6 kg; body fat: 43.3 ± 5.2%) were randomized to soccer training (SOC, n = 21) or control (CON, n = 20). SOC performed three weekly training sessions for 15 weeks, whereas CON had no training or lifestyle changes during the same period. Cardiac structure and function were assessed by echocardiography pre-intervention and post-intervention. RESULTS: Soccer training increased (P = 0.001) left ventricular mass index by 10% [95% CI 4; 15], while no changes occurred in CON (time × group interaction, P = 0.005). In addition, only SOC demonstrated a within-group increase (P = 0.01) of 8% [95% CI 2; 14] in left ventricular septum diameter. For markers of right ventricular remodelling, a within-group increase (P = 0.02) occurred for tricuspid annulus plane systolic excursion of 8% [95% CI 1; 14] in SOC only. Left atrial diameter index increased (P < 0.001) by 6% [95% CI 3; 10] after SOC, while it was unaffected in CON (time × group interaction, P = 0.02). For makers of diastolic function, SOC demonstrated a within-group increase (P = 0.02) in the average early diastolic mitral annulus velocity of 10% [95% CI 2; 19]. In addition, a reduction (P < 0.001) in mitral valve A velocity of - 19% [95% CI - 29; - 10] was observed following soccer training, which manifested in increased (P < 0.001) mitral valve E/A ratio of 34% [95% CI 16; 53] in SOC. No within-group changes were apparent in CON. CONCLUSION: In sedentary, mildly hypertensive, middle-aged women, 15 weeks of soccer training increases left ventricular mass and left atrial diameter and improves indices of left ventricular diastolic function.

High Lipoprotein(a) May Explain One-Quarter of Clinical Familial Hypercholesterolemia Diagnoses in Danish Lipid Clinics.

CONTEXT: Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH). OBJECTIVE: We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH. METHODS: Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a). RESULTS: We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a). CONCLUSION: Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.

Genetic testing increases the likelihood of a diagnosis of familial hypercholesterolaemia among people referred to lipid clinics: Danish national study.

BACKGROUND AND AIMS: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH. METHODS: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice. RESULTS: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant. CONCLUSIONS: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening.

The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial.

BACKGROUND: Depression following acute coronary syndrome is prevalent and associated with increased mortality and morbidity. Melatonin may function as a primary prophylactic antidepressant substance and alleviate depressive symptoms. The study was undertaken to determine if melatonin administered following an acute coronary syndrome (ACS) could prevent development of depression. METHODS: The study was a double-blinded, placebo-controlled, multicenter, randomized clinical trial performed in five primary care cardiology departments at Zealand, Denmark. Included patients were adults patients, free of depression at baseline, included at the latest 4 weeks after acute coronary syndrome. Twenty-five mg melatonin or placebo was administered 1 h before participants' bedtime for 12 weeks. The primary outcome is Major Depression Inventory (MDI) measured every two weeks throughout the trial. Incidence of depression was apriori defined as MDI score ≥ 21 during the trial. Reported exploratory outcomes were patterns of dropout and safety outcomes. RESULTS: 1220 patients were screened and 252 participants were randomized in a 1:1 ratio. Baseline MDI score in the melatonin and placebo group were, respectively, 6.18 (CI 5.32-7.05) and 5.98 (CI 5.19-6.77). No significant intergroup differences were found during the study in the intention-to-treat analysis or per-protocol analysis. Cumulative events of depressive episodes during the 12 weeks were six in the melatonin group and four in the placebo group. A significant drop in depressive symptoms were present throughout the study period. No intergroup differences were present in dropouts or adverse events. CONCLUSIONS: Melatonin showed no prophylactic antidepressant effect following acute coronary syndrome. The non-significant results might be due to a type II error or melatonin might not be able to prevent development of depressive symptoms following ACS.

The effect of MElatonin on Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS): study protocol for a randomized controlled trial.

BACKGROUND: Depression following acute coronary syndrome (ACS) constitutes a serious and debilitating problem. Approximately one in five patients will develop significant depression following ACS and less severe depressive symptoms are even more frequent. Furthermore, anxiety symptoms and sleep-wake disturbances are frequent. The objective of the MEDACIS trial is to investigate whether prophylactic treatment with melatonin has a preventive effect on depression, depressive and anxiety symptoms, sleep, and circadian disturbances following ACS. METHODS/DESIGN: "The effect of MElatonin and Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome" trial (MEDACIS) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial. A total of 240 patients with ACS and no depressive symptoms will be included in the trial for treatment with either 25 mg melatonin or placebo for a 12-week period. Development and severity of depressive symptoms will be evaluated using Major Depression Inventory every 2 weeks with the purpose of investigating the potential preventive effect of melatonin on depressive symptoms. DISCUSSION: Previously, only selective serotonin reuptake inhibitors (SSRIs) have been investigated in a primary preventive setup in patients following ACS. However, SSRIs are associated with several side effects. An ideal intervention would constitute the highest degree of prevention of depressive symptoms with the lowest risk of side effects. In this regard, melatonin may have advantages due to its low toxicity as well as its proven anxiolytic and hypnotic effects. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02451293 . Registered on 12 May 2015. EudraCT nr. 2015-002116-32.

[High volume exercise can be unhealthy]. / Supermotionisme og helbred.

There are positive health effects of exercise performed at regular intervals also in high volume exercisers. However, at present there is no exact definition of the optimal dose or the maximal safe dose of exercise, nor can the level of exercise to induce increased risk of harmful effects be defined. People who often exercise with a high volume and intensity should therefore individually consider the health-related effects and possible risks of their training as well as the physical or psychological warning signals.

Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the 'FC Prostate' randomized controlled trial.

BACKGROUND: Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The 'Football Club (FC) Prostate' study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. METHODS/DESIGN: Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2-3 times/week for 45-60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. DISCUSSION: The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01711892.

Cardiovascular effects of 3 months of football training in overweight children examined by comprehensive echocardiography: a pilot study.

We examined effects of a 3-month football training programme in overweight children using comprehensive echocardiography and peripheral arterial tonometry. Twenty preadolescent overweight children (17 boys, 3 girls aged 8-12 yrs; body mass index [BMI] ≥ 85(th) percentile) participated in a structured 3-month football training programme, consisting of 4 weekly 60-90 min sessions with mean heart rate (HR) > 80% of HRmax (football group, FG). A parallel control group (CG) included 11 children (7 boys, 4 girls) of equivalent age from an obesity clinic. After 3 months, systolic blood pressure was unchanged in FG, but had increased in CG (112 [s 6] vs. 122 [10] mmHg, P = 0.02). FG demonstrated increased left ventricular (LV) posterior wall diameter (0.60 [0.07] vs. 0.68 [0.10] cm, P < 0.001) and an improved right ventricular systolic function determined by tricuspid annular plane systolic excursion (TAPSE, 2.01 [0.29] vs. 2.27 [0.28] cm, P = 0.003). Measures of LV systolic function showed only discrete alterations and two-dimensional (2D) global strain was not changed. After 3 months, global isovolumetric relaxation time (IVRTglobal) had increased in FG (64.0 [7.5] vs. 73.9 [9.4] ms, P < 0.001) while other examined LV diastolic function variables were not altered. No echocardiographic changes were observed in CG. Between-group differences in pre-post delta values were observed for systolic blood pressure, TAPSE, and IVRTglobal (P = 0.02-0.03). We conclude that short-term football training may have positive structural and functional effects on the cardiovascular system in overweight preadolescent children.

Cardiovascular health profile of elite female football players compared to untrained controls before and after short-term football training.

This study examined the intermittent exercise performance and cardiovascular health profile in elite female football players in comparison to untrained young women, as well as a subgroup subjected to football training 2x1 h · week(-1) for 16 weeks. Twenty-seven Danish national team players (elite trained, ET) and 28 untrained women (UT) underwent dual-energy X-ray absorptiometry-scanning (DXA), comprehensive transthoracic echocardiography, treadmill and Yo-Yo Intermittent Endurance level 2 (IE2) testing. Eight women in UT were also tested after the football training period. Maximal oxygen uptake rate (VO2max), peak ventilation and peak lactate were 40, 18 and 51% higher (P< 0.01) in ET than UT, respectively. Cardiac dimensions and function were greater in ET than UT, with left ventricular diastolic diameter, right ventricular diastolic diameter, tricuspid annular plane systolic excursion (TAPSE) and peak transmitral flow in early diastole divided by peak transmitral flow velocity in late diastole during atrial contraction (E/A-ratio) being 13, 19, 27 and 41%, respectively, greater in ET than UT (P< 0.001 to< 0.05). Yo-Yo IE2 performance was 7-fold higher in ET than UT (1772 ± 508 vs. 234 ± 66 m, P< 0.001), fat mass was 51% lower (P< 0.001) and high density lipoprotein (HDL) cholesterol levels were 20% higher (P< 0.01). Sixteen weeks of football elevated VO2max and Yo-Yo IE2 performance by 16 and 40%, respectively, and lowered fat mass by 6%. Cardiac function was markedly improved by 16 weeks of football training with 26 and 46% increases in TAPSE and E/A ratio, respectively, reaching levels comparable to ET. In summary, elite female football players have a superior cardiovascular health profile and intermittent exercise performance compared to untrained controls, but short-term football training can markedly improve the cardiovascular health status.

Soccer training improves cardiac function in men with type 2 diabetes.

INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease, which is worsened by physical inactivity. Subclinical myocardial dysfunction is associated with increased risk of heart failure and impaired prognosis in T2DM; however, it is not clear if exercise training can counteract the early signs of diabetic heart disease. PURPOSE: This study aimed to evaluate the effects of soccer training on cardiac function, exercise capacity, and blood pressure in middle-age men with T2DM. METHODS: Twenty-one men age 49.8 ± 1.7 yr with T2DM and no history of cardiovascular disease participated in a soccer training group (n = 12) that trained 1 h twice a week or a control group (n = 9) with no change in lifestyle. Examinations included comprehensive transthoracic echocardiography, measurements of blood pressure, maximal oxygen consumption (V(˙)O(2max)), and intermittent endurance capacity before and after 12 and 24 wk. Two-way repeated-measures ANOVA was applied. RESULTS: After 24 wk of soccer training, left ventricular (LV) end-diastolic diameter and volume were increased (P < 0.001) compared to baseline. LV longitudinal systolic displacement was augmented by 23% (P < 0.001) and global longitudinal two-dimensional strain increased by 10% (P < 0.05). LV diastolic function, determined by mitral inflow (E/A ratio) and peak diastolic velocity E', was increased by 18% (P < 0.01) and 29% (P < 0.001), respectively, whereas LV filling pressure E/E' was reduced by 15% (P = 0.05). Systolic, diastolic, and mean arterial pressures were all reduced by 8 mm Hg (P < 0.01, P < 0.001, and P < 0.001, respectively). V(˙)O(2max) and intermittent endurance capacity was 12% and 42% (P < 0.001) higher, respectively. No changes in any of the measured parameters were observed in control group. CONCLUSION: Regular soccer training improves cardiac function, increases exercise capacity, and lowers blood pressure in men with T2DM.

Short-term street soccer improves fitness and cardiovascular health status of homeless men.

This study examined the effect of 12 weeks of small-sided street soccer (2.2 ± 0.7 sessions/week) and fitness center training (0.5 ± 0.2 sessions/week) on physical fitness and cardiovascular health profile for homeless men. Exercise capacity, maximal oxygen uptake (VO(2max)), body composition (DXA scans), blood pressure (BP), and blood lipid profile were determined before and after the intervention period for 22 soccer-group subjects (SG) and 10 waiting list controls (CO). In addition, time-motion analyses, HR measurements, and pedometer recordings were performed during street soccer training and daily-life activities. During a 60 min 4 versus 4 street soccer session 182 ± 62 intense running bouts were performed; mean HR was 82 ± 4% HR(max) and HR was >90% HR(max) for 21 ± 12% (±SD) of total time. On a day without training the participants performed 10,733 ± 4,341 steps and HR was >80% HR(max) for 2.4 ± 4.3 min. In SG, VO(2max) was elevated (p < 0.05) from 36.7 ± 7.6 to 40.6 ± 8.6 ml/min/kg after 12 weeks and incremental cycle test performance was improved (p < 0.05) by 81 s (95% CI: 47-128 s). After 12 weeks, fat percentage (19.4 ± 8.5 to 17.5 ± 8.6%) and LDL cholesterol (3.2 ± 1.1 to 2.8 ± 0.8 mmol L(-1)) were lowered (p < 0.05) in SG. The observed changes in SG were different (p < 0.05) from CO and no intra-group changes occurred for CO (p > 0.05). BP was unaltered after 12 weeks (p > 0.05), but diastolic BP was lowered for all SG subjects with pre-values >75 mmHg (83 ± 6 to 76 ± 6 mmHg, n = 8, p < 0.05). In conclusion, the exercise intensity is high during street soccer and regular street soccer training can be used as an effective activity to promote physical fitness and cardiovascular health status for homeless men.

[Heart screening of elite athletes]. / Hjertescreening af eliteatleter.

Sudden cardiac death in competing athletes is usually caused by unsuspected heart disease, and pre-participation screening may reduce the incidence of this tragic event. Although the cost-effectiveness of screening programs is unclear, international sports associations are currently implementing mandatory screening of elite athletes. During the first year of screening in the top Danish soccer league, all athletes were found to be eligible for continued participation in the game, suggesting that concern about false positive screening results may be exaggerated.

Natriuresis induced by mild hypernatremia in humans.

The hypothesis that increases in plasma sodium induce natriuresis independently of changes in body fluid volume was tested in six slightly dehydrated seated subjects on controlled sodium intake (150 mmol/day). NaCl (3.85 mmol/kg) was infused intravenously over 90 min as isotonic (Iso) or as hypertonic saline (Hyper, 855 mmol/l). After Hyper, plasma sodium increased by 3% (142.0 +/- 0.6 to 146.2 +/- 0.5 mmol/l). During Iso a small decrease occurred (142.3 +/- 0.6 to 140.3 +/- 0.7 mmol/l). Iso increased estimates of plasma volume significantly more than Hyper. However, renal sodium excretion increased significantly more with Hyper (291 +/- 25 vs. 199 +/- 24 micromol/min). This excess was not mediated by arterial pressure, which actually decreased slightly. Creatinine clearance did not change measurably. Plasma renin activity, ANG II, and aldosterone decreased very similarly in Iso and Hyper. Plasma atrial natriuretic peptide remained unchanged, whereas plasma vasopressin increased with Hyper (1.4 +/- 0.4 to 3.1 +/- 0.5 pg/ml) and decreased (1.3 +/- 0.4 to 0.6 +/- 0.1 pg/ml) after Iso. In conclusion, the natriuretic response to Hyper was 50% larger than to Iso, indicating that renal sodium excretion may be determined partly by plasma sodium concentration. The mechanism is uncertain but appears independent of changes in blood pressure, glomerular filtration rate, the renin system, and atrial natriuretic peptide.