Cytokine responses of CD4+ T cells and NKT cells to periodontitis-associated bacteria in individuals with or without periodontitis.

AIM: Periodontitis is an inflammatory disease driven by opportunistic bacteria including Porphyromonas gingivalis and Fusobacterium nucleatum, where T-cell and NKT-cell responses to these bacteria in patients with periodontitis grade B or C are not fully elucidated. The objective is to determine if exaggerated proinflammatory Th-cell responses to periodontitis-associated bacteria, but not commensal bacteria, is a characteristic of increased periodontitis grade. METHODS: Mononuclear cells from patients with periodontitis grade C (n = 26) or grade B (n = 33) and healthy controls (HCs; n = 26) were stimulated with P. gingivalis, F. nucleatum or the commensal bacteria, Staphylococcus epidermidis and Cutibacterium acnes. Cytokine production by different T-cell populations and FOXP3-expression by regulatory T cells were assessed by flow cytometry. RESULTS: Compared to HCs, grade C patients had decreased frequencies of interleukin (IL)-10-producing CD4+ T cells before stimulation (p = .02) and increased frequencies of IFN-y-producing CD4+ T cells after stimulation with P. gingivalis (p = .0019). Grade B patients had decreased frequencies of FOXP3+ CD4+ T cells before (p = .030) before and after stimulation with anti-CD2/anti-CD3/anti-CD28-loaded beads (p = .047), P. gingivalis (p = .013) and S. epidermidis (p = .018). Clinical attachment loss correlated with the frequencies of IFN-y-producing Th1 cells in P. gingivalis- and F. nucleatum-stimulated cultures in grade B patients (p = .023 and p = .048, respectively) and with the frequencies of Th17 cells in P. gingivalis-stimulated cultures (p = .0062) in grade C patients. Patients with periodontitis grade C or grade B showed lower frequencies of IL-10-producing NKT cells than HCs in unstimulated cultures (p = .0043 and p = .027 respectively). CONCLUSIONS: Both periodontitis groups showed decreased frequencies of immunoregulatory T-cell and NKT cell subsets at baseline. Clinical attachment loss correlated with P. gingivalis-induced Th17-responses in grade C patients and with Th1-responses in grade B patients when cells were stimulated with P. gingivalis, supporting that dysregulated pro-inflammatory T-cell responses to periodontitis-associated bacteria contribute to the pathogenesis of periodontitis.

Treated periodontitis and recurrent events after first-time myocardial infarction: A Danish nationwide cohort study.

AIM: To investigate the association between previous periodontal treatment and recurrent events after first-time myocardial infarction (MI). MATERIALS AND METHODS: From the Danish nationwide registries, patients with first-time MI between 2000 and 2015 were divided into three groups according to oral health care within 1 year prior to first-time MI. A multiple logistic regression model provided adjusted odds ratios (ORs) with 95% confidence intervals (CIs) to assess the 3-year risk of major adverse cardiovascular events (MACE). RESULTS: A total of 103,949 patients were included. Patients with treated periodontitis (PD) prior to first-time MI had an adjusted 3-year risk of MACE similar to patients presumed periodontally healthy (OR 0.97 [95% CI 0.92-1.03]). Patients with no prior dental visits were significantly older, had more comorbidities and showed significantly increased adjusted 3-year risks of MACE (OR 1.47 [95% CI 1.42-1.52]), cardiovascular death (OR 1.71 [95% CI 1.64-1.78]) and heart failure (OR 1.13 [95% CI 1.07-1.20]) compared with patients presumed periodontally healthy. CONCLUSIONS: Patients with treated PD 1 year prior to first-time MI had a similar risk of recurrent cardiovascular events as patients presumed periodontally healthy. No dental visit prior to first-time MI was an independent risk factor for recurrent events.

Blood Cell Biomarkers of Inflammation and Cytokine Levels as Predictors of Response to Biologics in Patients with Psoriasis.

For people with psoriasis, biomarkers aiding in the personalization of treatment with biologics are needed. We examined the usefulness of several biomarkers of inflammation in this respect. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) were measured in patients with psoriasis initiating TNF-α inhibitors (n = 131), IL-17/IL-17R inhibitors (n = 65), or IL-23/IL-12/23 inhibitors (n = 50). The blood levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, interferon (IFN)-γ, IL-17A, IL-6, soluble IL-6 receptor (sIL-6R), and soluble IL-6 signal transducer (sIL-6ST) were measured in patients initiating adalimumab (n = 62) or IL-17/IL-17R inhibitors (n = 24). Treatment response was defined by a psoriasis area and severity index (PASI) ≤ 2 three months after treatment initiation. Responders to TNF-α inhibitors had a lower NLR at baseline than non-responders (median and interquartile range (IQR) 2.15 (1.67-2.86) vs. 2.54 (1.88-3.55); p = 0.04). Responders to treatment with adalimumab had lower IL-6 levels at baseline than non-responders (0.99 (0.42-1.4) vs. 1.62 (0.96-2.41) pg/mL; p = 0.02). For the majority of patients, the IL-17A, IL-1ß, and IFN-γ levels were below quantification limits. NLR and IL-6 may serve as predictive biomarkers of treatment response to TNF-α inhibitor therapy in patients with psoriasis.

Cardiovascular Diseases and Periodontitis.

Periodontitis is a chronic inflammatory disease of the tooth-supporting connective tissue and alveolar bone that is initiated by a bacterial biofilm in periodontal pockets. It affects about half of adults in the Western world, and is associated with a range of systemic comorbidities, e.g., cardiovascular disease (CVD), diabetes and rheumatoid arthritis, and these diseases share overlapping systemic and target tissue inflammatory mechanisms. Indeed, mounting evidence has indicated that their association is causal and built on the presence of systemic low-grade inflammation (LGI). Prior research linking periodontitis to CVD has mainly been derived from experimental studies, observational data, and small interventional trials with surrogate markers of CVD, e.g., endothelial dysfunction. However, recent data from randomised studies have demonstrated that intensive treatment of periodontitis can reduce blood pressure in patients with hypertension in conjunction with reduction of systemic inflammatory markers. Furthermore, targeted anti-inflammatory therapy has been shown to reduce recurrent events in patients with established CVD and LGI. Along this line, the concept of residual inflammatory risk has emerged as an independent new risk factor for atherothrombotic CVD. The present review summarizes translational evidence indicating that periodontitis is a risk factor for CVD dependent on LGI, and we conclude that treatment of periodontitis is likely to contribute importantly to reduction of residual inflammatory risk.

IL-17 Pathway Members as Potential Biomarkers of Effective Systemic Treatment and Cardiovascular Disease in Patients with Moderate-to-Severe Psoriasis.

Psoriasis is a chronic inflammatory condition associated with atherosclerotic cardiovascular disease (CVD). Systemic anti-psoriatic treatments mainly include methotrexate and biological therapies targeting TNF, IL-12/23 and IL-17A. We profiled plasma proteins from patients with moderate-to-severe psoriasis to explore potential biomarkers of effective systemic treatment and their relationship to CVD. We found that systemically well-treated patients (PASI < 3.0, n = 36) had lower circulating levels of IL-17 pathway proteins compared to untreated patients (PASI > 10, n = 23). Notably, IL-17C and PI3 were decreased with all four examined systemic treatment types. Furthermore, in patients without CVD, we observed strong correlations among IL-17C/PI3/PASI (r ≥ 0.82, p ≤ 1.5 × 10-12) pairs or between IL-17A/PASI (r = 0.72, p = 9.3 × 10-8). In patients with CVD, the IL-17A/PASI correlation was abolished (r = 0.2, p = 0.24) and the other correlations were decreased, e.g., IL-17C/PI3 (r = 0.61, p = 4.5 × 10-5). Patients with moderate-to-severe psoriasis and CVD had lower levels of IL-17A compared to those without CVD (normalized protein expression [NPX] 2.02 vs. 2.55, p = 0.013), and lower IL-17A levels (NPX < 2.3) were associated with higher incidence of CVD (OR = 24.5, p = 0.0028, 95% CI 2.1-1425.1). As a result, in patients with moderate-to-severe psoriasis, we propose circulating IL-17C and PI3 as potential biomarkers of effective systemic anti-psoriatic treatment, and IL-17A as potential marker of CVD.

Peptidylarginine Deiminase 2 Gene Polymorphisms in Subjects with Periodontitis Predispose to Rheumatoid Arthritis.

Epidemiologic studies have shown associations between periodontitis and rheumatoid arthritis (RA), but a causal relationship has not been established. Citrullination of gingival proteins by human peptidylarginine deiminases (PADs) or PAD from Porphyromonas gingivalis has been proposed to generate autoantigens in anti-CCP-positive RA. This study investigated whether the association between periodontitis and RA is influenced by single nucleotide polymorphisms (SNPs) in the genes encoding PAD2 and PAD4 that catalyze aberrant citrullination in RA and often are overexpressed in inflamed gingival connective tissue in subjects with periodontitis. The study included 137 RA patients and 161 controls with self-reported periodontitis. Periodontitis onset preceded RA onset by 13 years on average and was not associated with any of the SNPs investigated. In subjects with periodontitis, carriage of the minor alleles of rs2057094 and rs2235912 in PADI2 significantly increased the risk of RA (odds ratios 1.42 [p = 0.03] and 1.48 [p = 0.02], respectively), and this effect was driven by the anti-CCP-negative RA patients. The minor alleles of these SNPs only increased risk of anti-CCP-positive RA in individuals with periodontitis and a history of smoking. These data suggest that individuals with periodontitis carrying the minor alleles of SNPs rs2057094, rs2076616 and rs2235912 in PADI2 may be at increased risk of RA.

Predictors of 10-Year Stent-Related Adverse Outcomes after Coronary Drug-Eluting Stent Implantation: The Importance of Stent Size.

INTRODUCTION: The predictors of stent treatment failure and their importance 10 years after treatment with drug-eluting stents (DESs) have not been reported in detail. METHODS: Data were retrieved from the SORT-OUT II database encompassing 2,849 non-left main coronary lesions in 2,073 unselected all-comer patients treated with first-generation DES and followed clinically for 10 years. Stent treatment failure (STF) was defined as definite or probable stent thrombosis, target lesion revascularization (TLR), or >70% restenosis left untreated. Target lesion failure (TLF) was defined as cardiac death, target vessel myocardial infarction, or TLR. Characteristics predicting higher hazard ratios (HRs) were identified by the multivariate Cox regression analysis. RESULTS: A stent diameter ≤2.5 versus ≥3.5 mm had STF 23.3 versus 11.8% and TLF 27.9 versus 18.8%. Stent length <20 versus >40 mm had STF 13.0 versus 29.0% and TLF 18.7 versus 34.6%. In multivariate analysis, decreasing stent diameter (HR: 1.24 [3.0 mm] to 2.12 [2.25 mm], reference ≥3.5 mm) and increasing stent length (HR: 1.15 [20-30 mm] to 2.07 [>40 mm], reference <20 mm) predicted STF together with diabetes (HR: 1.31), previous revascularization (HR: 1.31), restenotic (HR: 2.25), bifurcation (HR: 1.45), and chronically occluded lesions (HR: 1.54). A predictive score (PS) was calculated for each lesion from the HRs for the predictors present. The 10-year rates of STF were 10% in lesions with a PS ≤ 1.5 and 37% in those with PS ≥ 3.5. CONCLUSIONS: Ten-year outcomes show large variations depending on the stent size and a few patient and lesion characteristics. The calculation of a PS from these unambiguous variables may be used to improve the risk estimate in individual lesions and patients.

Neutrophil Pathways of Inflammation Characterize the Blood Transcriptomic Signature of Patients with Psoriasis and Cardiovascular Disease.

BACKGROUND: Patients with psoriasis have an increased risk of atherosclerotic cardiovascular disease (CVD). The molecular mechanisms behind this connection are not fully understood, but the involvement of neutrophils have drawn attention as a shared inflammatory factor. METHODS: RNA sequencing using the Illumina platform was performed on blood from 38 patients with moderate to severe psoriasis; approximately half had prior CVD. The neutrophil to lymphocyte ratio (NLR) was obtained from blood samples. Subclinical atherosclerosis was assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and ultrasound imaging. Transcriptomic analysis for differential expression and functional enrichment were performed, followed by correlation analyses of differentially expressed genes (DEGs), NLR and subclinical measurers of CVD. RESULTS: 291 genes were differentially expressed between patients with psoriasis with and without CVD. These included 208 upregulated and 83 downregulated DEGs. Neutrophil degranulation was identified as the most significant process related to the upregulated DEGs. Genes for the neutrophil-associated markers MPO, MMP9, LCN2, CEACAM1, CEACAM6 and CEACAM8 were identified as being of special interest and their mRNA levels correlated with NLR, high-sensitive C-reactive protein and markers of subclinical CVD. CONCLUSIONS: Patients with psoriasis and CVD had an increased expression of genes related to neutrophil degranulation in their blood transcriptome compared with patients with psoriasis without CVD. NLR may be a potential biomarker of subclinical CVD in psoriasis.

SuPAR is associated with death and adverse cardiovascular outcomes in patients with suspected coronary artery disease.

BACKGROUND: The inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with presence and severity of coronary artery disease (CAD) and incident death and myocardial infarction (MI). We sought to validate this finding in a further cohort of patients with suspected CAD. METHODS: Plasma suPAR was available in 1635 patients (73% with CAD) undergoing coronary angiography at a single regional Danish hospital between 2003 and 2005. Patients were followed for adverse cardiovascular outcomes of death, cardiac death and MI over a median follow-up of 4.2 years. RESULTS: In multivariate Cox models, adjusted for established cardiovascular risk factors, the biomarkers C-reactive protein, troponin-T and N-terminal-pro brain natriuretic peptide and the number of stenotic vessels, suPAR was independently associated with the combined endpoint of death/MI, hazard ratio (HR) 1.88; cardiovascular death, HR 2.01; and non-fatal MI, HR 1.53; (all p ≤ .037) per doubling of suPAR concentration. A plasma cutoff for suPAR ≥ 3.5 ng/mL was also significantly associated with death/MI, HR 1.51; p = .005. The C-statistic for the multivariate model predicting death/MI improved from 0.712 to 0.730 (p for difference .008) after inclusion of suPAR. However, suPAR was not associated with presence or extent of CAD (p > .05). CONCLUSION: These results validate previous findings that demonstrate suPAR to be an independent predictor of death/MI in patients with suspected or known CAD, however suPAR was not associated with presence or extent of CAD in our cohort. Probably because suPAR reflects end organ damage rather than the degree of atherosclerosis. BRIEF SUMMARY: We demonstrate that the inflammatory biomarker soluble urokinase plasminogen activator receptor is an independent predictor of death/myocardial infarction in patients with suspected or known coronary artery disease, but is not associated with the presence or severity of coronary artery disease.

Cardiovascular and metabolic health effects of team handball training in overweight women: Impact of prior experience.

PURPOSE: We tested the hypothesis that participation in small-sided team handball training could provide beneficial effects on cardiovascular and metabolic parameters in overweight premenopausal women with special focus on the importance of prior team handball experience. METHODS: A 16-week RCT training intervention was conducted in overweight premenopausal women randomized into three groups: a team handball training group without prior experience (UN; n = 13), a team handball group with prior experience (EXP; n = 10), and an inactive control group (CON; n = 9). Both UN and EXP completed 1.6 ± 0.3 training sessions per week with average heart rates of 84 ± 5 and 85 ± 9% of maximal heart rate, respectively. Cardiovascular and metabolic parameters were assessed before and after the intervention. RESULTS: Compared to CON, UN had significant increases in VO2max  (7 ± 4%) and intermittent endurance performance (26 ± 14%) as well as reduced total fat mass (4 ± 6%), total fat percentage (4 ± 5%), and android fat mass (7 ± 12%), respectively (all P < .05). Compared to UN and CON, EXP displayed increased left ventricular mass and left ventricular mass index (both P < .05) after the training period. There were no significant changes between any of the groups in muscle mass, blood lipids, resting heart rate, and blood pressure (all P > .05). CONCLUSION: Small-sided team handball training in overweight premenopausal women resulted in improvement of VO2max and body composition for participants with minimal team handball experience, indicating that prior team handball experience is not a prerequisite for improving physiological parameters of importance for health. Furthermore, EXP displayed cardiac adaptations, including increased left ventricular mass and left ventricular mass index.

Salivary microbiota and inflammation-related proteins in patients with psoriasis.

OBJECTIVE: The purpose of the present study was to characterize the composition of the salivary microbiota and quantify salivary levels of inflammation-related proteins (neutrophil gelatinase-associated lipocalin [NGAL] and transferrin) in patients with psoriasis and compare data to those obtained in patients with periodontitis and orally healthy controls, respectively. MATERIALS AND METHODS: Stimulated saliva samples from patients with psoriasis (n = 27), patients with periodontitis (n = 58), and orally healthy controls (n = 52) were characterized by means of next-generation sequencing of the 16S rRNA gene. Salivary levels of NGAL and transferrin were quantified using immunoassays. RESULTS: Linear discriminant effect size analysis showed that 52 (22 psoriasis-associated and 30 periodontitis-associated) and 21 (8 psoriasis-associated and 13 orally healthy control-associated) bacterial taxa differentiated the salivary microbiota in patients with psoriasis from that of patients with periodontitis and orally healthy controls, respectively. Significantly lower mean salivary levels of NGAL (psoriasis: 996 [std. error 320], periodontitis: 2,072 [295], orally healthy controls: 2,551 [345] ng/ml, p < .0001) and transferrin (psoriasis: 4.37 [0.92], periodontitis: 7.25 [0.88], orally healthy controls: 10.02 [0.94] ng/ml, p < .0001) were identified in patients with psoriasis. CONCLUSIONS: Psoriasis associates with characteristics of the salivary microbiota and salivary levels of inflammation-related proteins, which are different from characteristics in patients with periodontitis and orally healthy controls, respectively.

Short- and long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy in patients with mild left ventricular hypertrophy: a propensity score matching analysis.

AIMS: Based on European guidelines, alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) is indicated only in patients with interventricular septum (IVS) thickness >16 mm. The aim of this study was to evaluate the short- and long-term outcomes in ASA patients with mild hypertrophy (IVS ≤ 16 mm). METHODS AND RESULTS: We retrospectively evaluated 1505 consecutive ASA patients and used propensity score to match 172 pairs (344 patients) in groups IVS ≤ 16 mm or IVS > 16 mm. There was no occurrence of post-ASA ventriculoseptal defect in the whole cohort (n = 1505). Matched patients had 30-day mortality rate 0% in IVS ≤ 16 mm group and 0.6% in IVS > 16 mm group (P = 1). Patients in IVS ≤ 16 mm group had more ASA-attributable early complications (16% vs. 9%; P = 0.049), which was driven by higher need for pacemaker implantation (13% vs. 8%; P = 0.22). The mean follow-up was 5.4 ± 4.3 years and the annual all-cause mortality rate was 1.8 and 3.2 deaths per 100-patient-years in IVS ≤ 16 group and IVS > 16 group, respectively (log-rank test P = 0.04). There were no differences in symptom relief and left ventricular (LV) gradient reduction. Patients with IVS ≤ 16 mm had less repeated septal reduction procedures (log-rank test P = 0.03). CONCLUSION: Selected patients with HOCM and mild hypertrophy (IVS ≤ 16 mm) had more early post-ASA complications driven by need for pacemaker implantation, but their long-term survival is better than in patients with IVS >16 mm. While relief of symptoms and LV obstruction reduction is similar in both groups, a need for repeat septal reduction is higher in patients with IVS > 16 mm.

Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. METHODS: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. RESULTS: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023). CONCLUSIONS: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Coronary Artery Disease Assessed by Computed Tomography in Patients with Psoriasis: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with psoriasis have an increased risk of coronary artery disease (CAD) but data on coronary calcium score (CCS) and cardiac computed tomography angiography (CCTA) are inconsistent. OBJECTIVES: The present study quantitatively summarizes the literature data on the prevalence and burden of CAD in patients with psoriasis compared with controls using CCS and CCTA. METHODS: A systematic review and meta-analysis was conducted. The search included all studies examining CAD prevalence and burden detected by CCS with or without CCTA in patients with psoriasis without prior CAD compared with controls, between the year 2000 and May 30, 2018. RESULTS: Fourteen eligible studies provided data on 1,427 patients with psoriasis and 9,670 controls. Pooled data provided the estimated risk ratio (RR) of CAD and weighted mean differences of CCS in psoriasis patients versus controls. Meta-analysis of the prevalence and burden of CCS showed that patients with psoriasis had an increased risk of CAD (RR 1.14, 95% CI 1.04-1.26; p = 0.004), and for more severe CAD (CCS >100) the risk was further increased (RR 1.71, 95% CI 1.28-2.30; p < 0.001) compared with controls. Weighted mean difference for CCS was significantly higher in patients with psoriasis (12.74, 95% CI 10.70-14.78; p < 0.001). The risk of high-risk coronary plaques identified by CCTA was also significantly higher in psoriasis patients compared with controls (RR 1.77, 95% CI 1.37-2.28; p < 0.001). CONCLUSIONS: Patients with psoriasis have a higher prevalence of subclinical CAD, a higher burden of the disease, and more high-risk coronary plaques compared with controls without psoriasis.

Coronary microvascular dysfunction is associated with cardiac time intervals in women with angina and no obstructive coronary artery disease: An iPOWER substudy.

BACKGROUND: Coronary microvascular dysfunction (CMD) may cause angina in the absence of obstructive coronary artery disease (CAD) and increases the risk of future adverse cardiovascular events. Transthoracic Doppler echocardiography (TTDE) with pharmacological stress can assess coronary flow velocity reserve (CFVR), a measure of coronary microvascular function. However, simpler methods would be preferable for diagnosing CMD. Therefore, we examined the relationship between CFVR and cardiac time intervals measured by TTDE in a cohort of women with angina and no obstructive CAD. METHODS: In a prospective cohort study, we included 389 women with angina, left ventricular ejection fraction > 45%, and no obstructive CAD. CMD was defined as CFVR < 2.0. The study population was divided into three groups according to cutoff values of CFVR < 2, 2 ≤ CFVR ≤ 2.5, and CFVR > 2.5. Isovolumic contraction time (IVCT), ejection time (ET), and isovolumic relaxation time (IVRT) were measured by tissue Doppler M-mode, and the myocardial performance index (MPI = (IVCT + IVRT)/ET) was calculated. RESULTS: Coronary microvascular dysfunction was associated with increasing age, hypertension, higher resting heart rate, and lower diastolic blood pressure. Moreover, CMD was associated with higher E/e' ratio (P = 0.002) and longer IVCT (P < 0.001), higher MPI (P < 0.001) and shorter ET (P = 0.002), but not with IVRT or conventional measures of left ventricular geometry, mass, and function. In multivariable analysis, longer IVCT (P < 0.001) and higher MPI (P = 0.002) remained associated with CMD. CONCLUSION: In women with angina and no obstructive CAD, CMD is associated with longer IVCT and higher MPI indicating a link between CMD and subtle alternations of systolic and combined measures of cardiac time intervals.

Cardiovascular adaptations after 10 months of intense school-based physical training for 8- to 10-year-old children.

This study examined cardiovascular adaptations in 8- to 10-year-old schoolchildren after 10 months (a full school year) of 3 × 40 minute per week of small-sided ball games (SSG, including football, basketball, and/or floorball) or circuit strength training (CST). The study involved 291 Danish schoolchildren, 8-10 years old, cluster-randomized to SSG (n = 93, 4 schools, 5 classes), CST (n = 83, 4 schools, 4 classes), or a control group (CON, n = 115, 2 schools, 5 classes). Before and after the 10-month intervention, resting heart rate and blood pressure measurements were performed as well as comprehensive transthoracic echocardiography and peripheral arterial tonometry (PAT). Analysis of baseline-to-10-months changes showed between-group differences (P < 0.05) after both training interventions in diastolic blood pressure (delta scores: SSG -2.1 ± 6.0 mm Hg; CST -3.0 ± 7.1 mm Hg; CON 0.2 ± 5.3 mm Hg). Moreover, there were between-group differences in delta scores (P < 0.05) in interventricular septum thickness (SSG 0.17 ± 0.87 mm; CST 0.30 ± 0.94 mm; CON -0.15 ± 0.68 mm), left-atrial volume index (SSG 0.32 ± 5.13 mL/m2 ; CON 2.60 ± 5.94 mL/m2 ), and tricuspid annular plane systolic excursion (SSG -0.4 ± 3.3 mm; CON: 0.1 ± 3.6 mm). No significant between-group differences were observed for the PAT-derived reactive hyperemia index. In conclusion, 10 months of 3 × 40 minutes per week of SSG and CST in 8- to 10-year-old children decreased diastolic blood pressure and elicited discrete cardiac adaptations, suggesting that intense physical exercise in school classes can have effects on cardiovascular health in children.

Positive effects on bone mineralisation and muscular fitness after 10†months of intense school-based physical training for children aged 8-10†years: the FIT FIRST randomised controlled trial.

OBJECTIVES: We investigated whether musculoskeletal fitness of school children aged 8-10 years was affected by frequent intense PE sessions. DESIGN AND PARTICIPANTS: 295 Danish school children aged 8-10 years were cluster randomised to a small-sided ball game group (SSG) (n=96, four schools, five classes), a circuit strength training group (CST) (n=83, four schools, four classes) or a control group (CON, n=116, two schools, five classes). INTERVENTION: SSG or CST was performed 3×40 min/week over 10 months. Whole-body dual-energy X-ray absorptiometry (DXA) scans were used to determine areal bone mineral density (aBMD), bone mineral content (BMC) and lean body mass (LBM). Flamingo balance, standing long jump and 20-m sprint tests were used to determine muscular fitness. RESULTS: Analysis of baseline-to-10 months change scores showed between-group differences in favour of the interventions in whole-body aBMD (SSG vs CON: 8 mg/cm2, 95% CI 3 to 13; CST vs CON: 7 mg/cm2, 95% CI 2 to 13, p<0.05) and leg BMC (SSG vs CON: 11 g, 95% CI 4 to 18; CST vs CON: 11 g, 95% CI 3 to 18, p<0.05). SSG had higher change scores in leg aBMD compared with CON and CST (SSG vs CON: 19 mg/cm2, 95% CI 11 to 39, p<0.05; SSG vs CST: 12 mg/cm2, 95% CI 3 to 21, p<0.05), and CST had higher change scores in whole-body BMC compared with CON (CST vs CON: 25 g, 95% CI 10 to 39, p<0.05). Both training types resulted in higher change scores in postural balance (SSG vs CON: 2.4 fewer falls/min, 95% CI 0.3 to 4.5, CST vs CON: 3.6 fewer falls/min, 95% CI 1.3 to 5.9, p<0.05) and jump length (SSG vs CON: 10%, 95% CI 5 to 16%; CST vs CON: 9%, 95% CI 3 to 15%, p<0.05). No between-group differences were observed for sprint performance or LBM (p>0.05). CONCLUSIONS: In conclusion, 3×40 min/week with SSG or CST over a full school year improves bone mineralisation and several aspects of muscular fitness of children aged 8-10 years, suggesting that well-organised intense physical education classes can contribute positively to develop musculoskeletal health in young children. TRIAL REGISTRATION NUMBER: NCT02000492, post results.

Nationwide Study on the Risk of Abdominal Aortic Aneurysms in Patients With Psoriasis.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a complex multifactorial disease associated with a high morbidity and mortality. Increased inflammation including T-helper 17 cell-mediated effects has been implicated in AAA pathogenesis. Psoriasis is considered to be a T-helper 17-driven chronic inflammatory disease and in view of potentially overlapping inflammatory mechanisms, we investigated the risk of AAA in patients with psoriasis in a nationwide cohort. APPROACH AND RESULTS: The study comprised all Danish residents aged ≥18 years followed up from January 1, 1997, until diagnosis of AAA, December 31, 2011, migration or death. Information on comorbidity, concomitant medication, and socioeconomic status was identified by individual-level linkage of administrative registers. Incidence rates for AAA were calculated and incidence rate ratios adjusted for age, sex, comorbidity, medications, socioeconomic status, and smoking were estimated in Poisson regression models. A total of 5 495 203 subjects were eligible for analysis. During the study period, we identified 59 423 patients with mild psoriasis and 11 566 patients with severe psoriasis. The overall incidence rates of AAA were 3.72, 7.30, and 9.87 per 10 000 person-years for the reference population (23 696 cases), mild psoriasis (240 cases), and severe psoriasis (50 cases), respectively. The corresponding adjusted incidence rate ratios for AAA were increased in patients with psoriasis with incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (confidence interval, 1.21-2.32) for subjects with mild and severe disease, respectively. CONCLUSIONS: In a nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of AAA. The mechanisms and consequences of this novel finding require further investigation.