Unfavorable Cardiovascular Risk Profile Research Articles

Exploring the sex difference in cardiovascular risk during Growth Hormone Therapy in adults.

Given the previously identified sex differences in cardiovascular morbidity and mortality in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT), our aim is to investigate sex specific differences in the efficacy of (long-term) GHRT on cardiovascular (CV) risk profile and disease in subjects with GHD. Our hypothesis is that women will experience less beneficial effects than men. Retrospective nationwide cohort study. We compared all men (n = 1335) and women (n = 1251) with severe GHD registered in the Dutch National Registry of GH Treatment in Adults database with respect to cardiovascular risk profile and morbidity at baseline and during follow-up. Men had a more unfavourable CV risk profile at baseline. During the first years of GHRT, the reduction in waist circumference, waist-to-hip ratio, total cholesterol and triglyceride levels was greater in men than in women (all p < 0.05). Between-sex differences in effects during later follow-up were less clear. No sex differences were found in the risk of developing non-fatal cardio- or cerebrovascular disease during GHRT. Our results suggest that men with GHD did indeed experience more beneficial effects of GHRT on body composition and lipoprotein metabolism than women, at least in the early years of treatment. Also, the more unfavourable CV risk profile at baseline in men did not translate into a sex difference in the risk of developing cardiovascular and cerebrovascular morbidity during GHRT.

Ethnic minorities treated with new-generation drug-eluting coronary stents in two European randomised clinical trials.

Several ethnic minorities have an increased risk of cardiovascular events, but previous European trials that investigated clinical outcome after coronary stenting did not assess the patients' ethnic background. To compare ethnic minority and Western European trial participants in terms of both cardiovascular risk profile and 1‑year clinical outcome after percutaneous coronary intervention. In the BIO-RESORT and BIONYX randomised trials, which assessed new-generation drug-eluting stents, information on patients' self-reported ethnic background was prospectively collected. Pooled patient-level data of 5803 patients, enrolled in the Netherlands and Belgium, were analysed in this prespecified analysis. The main endpoint was target vessel failure after 1year. Patients were classified as belonging to an ethnic minority (n = 293, 5%) or of Western European origin (n = 5510, 95%). Follow-up data were available in 5772 of 5803 (99.5%) patients. Ethnic minority patients were younger, less often female, more often current smokers, more often medically treated for diabetes, and more often had apositive family history of coronary artery disease. The main endpoint target vessel failure did not differ between ethnic minority and Western European patients (3.5% vs 4.9%, hazard ratio 0.71, 95% confidence interval 0.38-1.33; p = 0.28). There was also no difference in mortality, myocardial infarction, and repeat revascularisation rates. Despite the unfavourable cardiovascular risk profile of ethnic minority patients, short-term clinical outcome after treatment with contemporary drug-eluting stents was highly similar to that in Western European patients. Further efforts should be made to ensure the enrolment of more ethnic minority patients in future coronary stent trials.

Evaluation of the relation between subclinical systolic dysfunction defined by four-dimensional speckle-tracking echocardiography and growth differentiation factor-15 levels in patients with acromegaly.

In patients with acromegaly, the long-term presence of elevated GH and IGF-1 levels is associated with an unfavorable cardiovascular risk profile. We aimed to assess the relationship of four-dimensional speckle tracking echocardiographic (4DSTE) measurements with growth differentiation factor-15 (GDF-15) levels and the Framingham Cardiovascular Risk Score (FRS) in patients with acromegaly. A single-center, cross-sectional study was conducted. The study included 40 acromegaly and 32 age- and gender-matched controls. Anthropometric, biochemical, and echocardiographic assessments were performed. GDF-15 levels were measured using ELISA. In the controlled acromegaly group, global longitudinal (GLS), circumferential (GCS), area (GAS), and radial (GRS) strain measurements identified by 4DSTE were lower than those of the controls (p < 0.05). Moreover, strain parameters were lower in active acromegaly patients than in controls, but the difference was not statistically significant. The GLS was negatively correlated with age, the estimated disease duration, and FRS. Serum GDF-15 levels showed no significant difference between the acromegaly and control groups. In patients with acromegaly, serum GDF-15 levels were positively correlated with age, waist-to-hip ratio, systolic and diastolic blood pressure, FRS, fasting plasma glucose, and HbA1c, but not with strain parameters. The multiple regression analysis revealed that FRS was an independent factor associated with serum GDF-15 levels in patients with acromegaly and the overall cohort (p < 0.001). Our study demonstrates that while LVEF was within normal limits, global strain parameters (GLS, GCS, GAS, and GRS) measured by using a novel imaging technique, 4DSTE, were lower in patients with acromegaly, suggesting the presence of subclinical systolic dysfunction in patients with acromegaly. GDF-15 can be a potential predictor of cardiovascular risk in patients with acromegaly.

Serum afamin and its implications in adult growth hormone deficiency: a prospective GH-withdrawal study.

Adult growth hormone deficiency (AGHD) is associated with a high prevalence of metabolic syndrome (MS), which contributes to the unfavorable cardiovascular risk profile in these patients. Insulin like growth factor-1 (IGF-1) is a widely used biomarker, however it does not always reflect the cardiometabolic risk and has a poor relationship with clinical efficacy endpoints. Consequently, there is an unmet need for biomarkers to monitor responses to GH-replacement. Afamin is a hormone-like glycoprotein, expressed in the liver. Higher afamin levels are strongly associated with MS and insulin resistance (IR). Although both MS and IR are very common in AGHD, afamin has not been investigated in these patients. To investigate afamin as a potential biomarker in patients with AGHD. Participants included 20 AGHD patients (11 GH-substituted and 9 GH-unsubstituted) and 37 healthy controls. Subjects underwent routine laboratory examinations, anthropometric measurements, body composition analysis using multi-frequency bioelectrical impedance analysis (InBody720) and measurement of serum afamin concentrations. In GH-substituted subjects, GH-substitution was withdrawn for 2 months. Measurements were carried out right before GH-withdrawal, at the end of the 2-month withdrawal period, and 1 month after reinstituting GH-replacement therapy (GHRT). GH-unsubstituted patients demonstrated higher afamin levels compared to controls (p=0.03). Afamin positively correlated with skeletal muscle mass, bone mineral content, total body water, extracellular- and intracellular water content, insulin (all, p<0.01), HOMA-IR (p=0.01) and C-peptide (p=0.03) levels in AGHD but not in healthy controls. In GH-substituted patients 2-month of GH-withdrawal caused significant changes in body composition, including decreased fat-free mass, skeletal muscle mass, total body water, and intracellular water content (all, p<0.01); but these changes almost fully recovered 1 month after reinstituting GHRT. Unexpectedly, afamin levels decreased after GH-withdrawal (p=0.03) and increased with reinstitution (p<0.01). Changes of afamin levels during GH-withdrawal positively correlated with changes of HOMA-IR (r=0.80; p<0.01) and changes of insulin (r=0.71; p=0.02). Higher afamin levels in unsubstituted AGHD patients might indicate severe metabolic dysregulation. Significant changes accompanying GH-withdrawal and reinstitution, along with strong correlations with measures of IR, suggest that afamin could be a promising biomarker to monitor GHRT-associated changes of insulin sensitivity.

No evidence for a diminished ovarian reserve among patients with hypertensive disorders of pregnancy: a case control study

BackgroundExisting evidence suggests a relation between cardiovascular dysfunction and diminished ovarian reserve. While it is known that pre-existent cardiovascular dysfunction is also associated with the development of preeclampsia (PE) during pregnancy, we hypothesize that signs of diminished ovarian reserve may occur more frequently among women with a history of hypertensive disorders of pregnancy (HDP). The aim of our study was therefore to analyse if women with a history of HDP show signs of diminished ovarian reserve, represented by lower anti-Mullarian hormone (AMH) levels, compared to controls. For this retrospective observational case control study, patients included women with a history of HDP, whereas controls constituted of women with a history of an uncomplicated pregnancy. The study was conducted in a tertiary referral centre in which all women underwent a one-time cardiovascular and metabolic assessment. Ovarian reserve and markers of cardiovascular function were evaluated, adjusted for age and body mass index (BMI) using linear regression analyses.Results163 patients and 81 controls were included over a time span of 3 years. No signs of diminished ovarian reserve i.e. lower AMH level were observed in the patient group versus controls. A subgroup analysis even showed higher AMH levels in late onset HDP as compared to controls (2.8 vs. 2.0 µg/L, p = 0.025). As expected, cardiovascular function markers were significantly less favourable in the patient group compared to controls; higher levels of systolic blood pressure (BP) (5%), diastolic BP (4%), triglycerides (29%), glucose (4%) and insulin levels (81%) (all p < 0.05), whereas high density lipid (HDL) cholesterol was 12% lower (NS).ConclusionsDespite unfavourable cardiovascular risk profile, the present study does not substantiate the hypothesis that women with HDP show accelerated ovarian ageing as compared to healthy parous controls. Although HDP patients should be warned about their cardiovascular health, they shouldn’t be concerned about unfavourable ovarian reserve status.

Abstract 151: Age‐Related Increases in Carotid Artery Calcification: Insights from NaF PET/CT Imaging

Introduction Atherosclerosis, the hardening and narrowing of the arteries, occurs due to the buildup of plaque on the inner walls of the arteries which can result in reduced blood flow to the organs and tissues. Risk factors such as smoking, chronic kidney disease, and aging can contribute to plaque formation. The gradual loss of elasticity in arterial walls and the presence of other risk factors, such as high blood pressure and diabetes, contribute to the increased risk of cardiovascular disease (CVD) observed in aging populations. Early detection through sensitive and specific imaging methods is important for the detection and treatment of CVD. 18F‐Sodium Fluoride positron emission tomography/computerized tomography (NaF‐PET/CT) can be utilized to detect and quantify molecular calcification and therefore early atherosclerosis in patients with CVD. Research has shown a positive correlation between NaF uptake in the common carotid arteries/thoracic aorta and cardiovascular/thromboembolic risk. This study aims to assess the effect of aging on NaF uptake in the left common carotid artery (LCC) in subjects with known cardiovascular risk factors. Methods In total, 36 subjects (mean age 55.4 ± 12.3 years, 50% males) with known cardiovascular risk factors underwent FDG‐PET/CT. Participants were recruited from a group of patients with chest pain syndromes who were referred for coronary CT angiography. Individuals who were not taking any blood pressure medications and who had a greater than 1% increased risk of fatal CVD, estimated by the systematic coronary risk evaluation tool, were eligible for inclusion into the at‐risk for CVD group. NaF PET/CT was performed 90 min after the intravenous injection of 2.2 MBq of NaF/kg. NaF uptake in the LCC was quantitatively assessed by measuring the blood‐pool‐corrected maximum standardized uptake value (SUVmean) on each axial slice. Pearson’s R was calculated and evaluated for significance in all variables. The threshold for significance was set at P &lt; 0.05. Results A significant association between age in patients with cardiovascular risk factors and NaF uptake in the LCC artery was found. Age positively correlated with NaF uptake (r=0.472, p= 0.004) across all 36 patients. Conclusion Our results demonstrate that NaF uptake increases in the LCC with age in subjects with known cardiovascular risk factors. The strong association between age and calcification of the carotid arteries within a population of individuals with unfavorable cardiovascular and thromboembolic risk profiles demonstrates the potential of NaF PET/CT. NaF PET/CT may allow physicians to evaluate effectiveness of treatment and determine a patient's risk for CVD. However, additional trials are needed to further evaluate the associations found in this study and determine relevance in a clinical setting.

Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population.

Caution has been advocated recently when using Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) patients with an unfavorable cardiovascular risk profile. We aimed to compare the incidences in cardiovascular events between JAKi or bDMARDs in a large population of RA patients. RA patients starting a new bDMARD or JAKi between August 1st 2018 and January 31st 2022 have been selected from IQVIA's Dutch Real-World Data Longitudinal Prescription database, covering about 63% of outpatient prescriptions in the Netherlands. Study outcome was a cardiovascular event, defined as the start of platelet aggregation inhibitors during study period. The incidence densities of cardiovascular events were compared between JAKi and bDMARDs using multilevel Poisson regression, adjusted for exposition time and confounders. 15 191 unique patients were included, with 28 481 patient-years on treatment with either JAKi (2,373) or bDMARDs (26 108). Most patients were female (72%) and median age was 62 years. We found 36 cardiovascular events (1.52 events/100 patient years) during therapy with JAKi and 383 events (1.47 events/100 patient years) during therapy with bDMARDs, respectively, resulting in an adjusted incidence rate ratio (IRR) of 0.99 for JAKi compared with bDMARDs (95% confidence interval (CI), 0.70-1.41). Sub-analyses in patients >65 years, by sex, or separately for tofacitinib and baricitinib, yielded similar results. In a large Dutch general RA population, the risk of cardiovascular events seems not different between JAKi users and those using bDMARDs, although a small increase in higher risk patients cannot be excluded.

Cardiovascular risk in myositis patients compared with the general population.

We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features. Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications. Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients. Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC.

Association of triglyceride levels with adverse cardiovascular events in patients with ST-segment elevation myocardial infarction

Although there is an established association between elevated triglyceride (eTG, ≥175 mg/dl) levels and adverse cardiovascular events, some studies have suggested that eTG levels may be linked to neutral or even improved clinical outcomes, particularly among patients with acute myocardial infarction. However, these studies had certain limitations, including small sample sizes, heterogeneous study populations, and inadequate statistical adjustments. To address these limitations, we conducted an analysis of 5347 patients with ST-segment elevation myocardial infarction (STEMI) between March 2003 and December 2020, using a prospective registry-based cohort from two large, regional STEMI centers. We used a triglyceride level of 175 mg/dl as the cutoff point for eTG levels. Of the study participants, 24.5% (n = 1312) had eTG levels. These patients were more likely to be younger, male, and have a higher number of cardiovascular risk factors compared to those with low TG levels. Despite these unfavorable cardiovascular risk profiles, patients with eTG levels had lower unadjusted risks of 1-year major adverse cardiac events (MACE) -a composite of myocardial infarction, stroke, and death- than those with low TG levels (8.8% vs. 11%, p = 0.034). However, after adjusting for certain clinical factors and lipid profile, eTG levels were not associated with a lower 1-year MACE (aHR: 1.10 (0.71–1.70), p = 0.7). In conclusion, a quarter of STEMI patients had eTG levels and these patients had comparable long-term cardiovascular outcomes compared to those with low TG levels after controlling for clinical factors and lipid profile.

Cardiorespiratory fitness and body fat percentage in young adults

Relevance. Maximal oxygen consumption (VO2max) is the maximum amount of oxygen an individual can breathe in and utilize it to produce energy aerobically. The global epidemic of overweight and obesity -’globesity’ is emerging as a public health problem in many parts of the world. Almost 30-65 % of adult urban Indians is either overweight or obese or has abdominal obesity. Recently, cardiovascular ailments are increasing in the younger generation. Low levels of cardiovascular fitness and unfavorable cardiovascular risk profiles are detected in them. Total body fatness and aerobic capacity are frequently used in association with each other and it is often implied that these parameters are strongly inter-related. Both body fatness and status aerobic fitness have been shown to be risk factors for future health outcomes. The aim of this study was to assess the correlation of cardio-respiratory fitness with body fat percentage in young adults. Materials and Methods. This was a pilot study conducted in a group of 100 subjects of age group 18 to 25 years. Ethical clearance was obtained from institutional ethical committee and written informed consent were taken from all subjects participated in the study. Following parameters were taken (a) anthropometric parameters, (b) body fat percentage, (c) physical activity level and (d) VO2max. Results and Discussion. The mean ± SD for age, height, weight, global physical activity questionnaire (GPAQ score) and VO2max was found to be higher in male participants as compared to female participants while BMI was almost equal in both the genders but body fat percentage was higher in female participants. There was positive non-significant correlation of VO2max with body mass index and global physical activity in female subjects but positive significant in male subjects. And moderate negative correlation between body fat percentage and VO2max in male and female subjects but not significant (p 0.05). Conclusion. Body fat percentage was negatively correlated with maximum oxygenconsumption (VO2 max).

Ten-year atherosclerotic cardiovascular disease risk prediction for postmenopausal women: Impacts of isolated postchallenge hyperglycemia.

Isolated postchallenge hyperglycemia (IPH) is a type of diabetes mellitus defined as 2-h glucose ≥200 mg/dL but fasting glucose <126 mg/dL. The purpose of the study was to assess impacts of IPH on 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores in postmenopausal women. This study analyzed data from 428 postmenopausal women who underwent oral glucose tolerance test at a medical center. Ten-year ASCVD risk was evaluated by using Pooled Cohort Equations. Logistic regression analysis was performed to estimate odds ratios for having high 10-year ASCVD risk scores (≥5%) among these women. The subjects with IPH had higher systolic blood pressure and worse lipid profile than those without IPH. Ten-year ASCVD risk scores for postmenopausal women with IPH were calculated under 2 scenarios: the IPH women were considered non-diabetic, they were designated as patients with DM. The median ASCVD risk score of the participants with IPH increased significantly from 3.7% under scenario 1 to 7.1% under scenario 2. Approximately 20% women with IPH were re-categorized from risk category of <5% to ≥7.5% once they were identified as patients with DM (scenario 2). The results of logistic regression analyses showed that IPH was independently positively associated with 10-year ASCVD risk scores ≥5% under both scenarios. Postmenopausal women with IPH were characterized by unfavorable cardiovascular risk profile and high predicted 10-year ASCVD risk. Knowing the women's hidden DM status would significantly alter their risk categorization.

Smoking in pregnancy is associated with increased adiposity and retinal arteriolar wall-to-lumen ratio in adolescence: The Copenhagen Child Cohort Study 2000.

To investigate the association between prenatal exposures and anthropometric data and cardiovascular risk factors including retinal arteriolar wall-to-lumen ratio in adolescence. This longitudinal observational study included all 1445 adolescents from the Copenhagen Child Cohort 2000 who attended the 2016-2017 examination. Outcome measures included retinal arteriolar wall-to-lumen ratio, height, body mass index, waist-to-hip ratio, body composition measured by bioimpedance, and blood pressure. Information on prenatal exposures (birth weight, gestational age, maternal smoking during pregnancy) as well as sex, parental age, household income and parental educational levels were obtained from national registries. Associations between exposures and outcome measures were analyzed using general linear models. Maternal smoking during pregnancy was associated with a higher retinal arteriolar wall-to-lumen ratio (0.004 or 1.9%, P=0.009) at age 16/17years, an association driven exclusively by the female participants (0.008 or 3.7%, P<0.0001). Maternal smoking during pregnancy was also associated to higher body-mass index (1.43kg/m2, P<0.0001), waist-to-hip ratio (0.02, P<0.0001) and fat mass index (0.93kg/m2, P<0.0001). Birth weight, gestational age, and parental age had no detectable impact on retinal arteriolar wall-to-lumen ratios. Prenatal exposure to tobacco smoking is associated with a higher risk of obesity and, predominantly in girls, to a greater retinal arteriolar wall thickness, which suggests that maternal smoking may induce an unfavorable cardiovascular and metabolic risk profile in the child.

Association between spicy foods consumption and cardiovascular disease risk factors: Guangzhou Biobank Cohort Study

BackgroundEvidence regarding the association of spicy foods intake with cardiovascular disease (CVD) risk factors was less clear, especially in those with diabetes. We hereby examined the association of spicy foods intake with CVD risk factors in older Chinese.MethodsThirty thousand three hundred twenty-five participants (72.34% women) aged 50+ years were recruited in the Guangzhou Biobank Cohort Study from 2003 to 2008. Information of spicy foods intake and disease history was collected by face-to-face interview. CVD risk factors were measured and treated as continuous variables. Diabetes was defined by a fasting plasma glucose (FPG) ≥7.0 mmol/L and/or self-reported physician-diagnosed diabetes.ResultsOf 30,325 participants, 12.9% consumed spicy foods regularly. After adjusting for multiple confounders, participants who consumed spicy foods of 5–7 days/week, versus none, had higher body mass index (1.18, 95% confidence interval (CI) 0.95 to 1.42 kg/m2), waist circumference (2.80, 95% CI 2.18–3.41 cm), waist-to-hip ratio (0.010, 95% CI 0.006 to 0.015), systolic blood pressure (2.44, 95% CI 0.92 to 3.97 mmHg), diastolic blood pressure (1.94, 95% CI 1.14 to 2.73 mmHg), FPG (0.310, 95% CI 0.188 to 0.432 mmol/L), triglycerides (0.185, 95% CI 0.096 to 0.273 mmol/L), and lower high-`density lipoprotein cholesterol (− 0.040, 95% CI − 0.069 to − 0.012 mmol/L). Similar results were found for the associations of spicy foods strength with CVD risk factors. The results attenuated slightly but not substantially across diabetes groups.ConclusionsOur study showed that higher frequency and strength of spicy foods intake were associated with unfavorable cardiovascular disease risk profile in older people, and such associations did not vary by diabetes status. Whether the results were causal needs to be determined in further studies.

Female fragile X premutation carriers are at increased risk for metabolic syndrome from early adulthood

Background and aimsWomen with primary ovarian insufficiency exhibit an unfavorable cardiovascular risk profile. A common cause for primary ovarian insufficiency is fragile X premutation (FXPC), and data on the cardiovascular risk factors in women with FXPC are scarce. We aimed to assess the prevalences of abnormal metabolic components among FXPC. Methods and resultsClinical, anthropometric and laboratory data were collected from 71 women with FXPC and compared to 78 women referred for counseling in an in-vitro fertilization clinic (control group). The mean ± SD ages of the FXPC and control groups were 33.5 ± 5.6 and 36.2 ± 5.3 years, respectively (p = 0.003). In a logistic regression analysis, the FXPC group had increased risks for hyperglycemia, hypertriglyceridemia, central obesity and low high-density lipoprotein cholesterol, of 21.8-fold (95% CI 2.7–175, p = 0.004), 6.9-fold (95% CI 2.5–18.7, p < 0.0001), 3.1-fold (95% CI 1.4–6.9, p = 0.005) and 2.4-fold (95% CI 1.1–5.2, p = 0.03), compared to the control group. The FXPC group had 2.7-fold higher prevalence of two abnormal metabolic components; 19% met the full criteria of MetS, compared to 3% of the control group. Neither CGG repeats nor ovarian reserve markers were associated with metabolic risk. ConclusionsCarriers of fragile X premutation are at increased metabolic risk from early adulthood; waist circumference, glucose and lipid levels are particularly elevated. We recommend metabolic screening for all women with FMR1 premutation, to enable early interventions for prevention of long-term cardiovascular comorbidities.

Proteomic profiling for detection of early-stage heart failure in the community

Abstract Background and purpose Biomarkers may provide insight into the molecular mechanisms underlying cardiac remodelling and dysfunction. Using a targeted proteomic approach, we aimed to identify circulating biomarkers associated with early-stage heart failure and extract a proteome-based risk classifier for this condition. Methods 575 community-based participants (mean age, 57 years; 51.7% women) underwent echocardiography and proteomic profiling (CVD II panel, Olink Proteomics). We applied partial least squares-discriminant analysis (PLS-DA) and a machine learning algorithm (extreme gradient boosting, XGBoost) to identify key proteins associated with echocardiographic abnormalities. We used Gaussian Mixture modelling for unbiased clustering to construct phenogroups based on influential proteins in PLS-DA and XGBoost. Results Of 87 proteins, 13 were important in PLS-DA and XGBoost modelling for detection of left ventricular (LV) remodelling, LV diastolic dysfunction and/or left atrial reservoir dysfunction: placenta growth factor, kidney injury molecule-1, prostasin, angiotensin-converting enzyme-2, galectin-9, cathepsin L1, matrix metalloproteinase-7, TNFR superfamily members 10A, 10B and 11A, interleukins-6 and 16 and alpha-1-microglobulin/bikunin precursor. Based on these proteins, the clustering algorithm divided the cohort into two distinct phenogroups, with each cluster grouping individuals with a similar protein profile. Participants belonging to the second cluster (n=118) were characterized by an unfavourable cardiovascular risk profile and adverse cardiac structure and function. The adjusted risk of presenting cardiac maladaptation was higher in this phenogroup than in the other cluster (P&amp;lt;0.0001). Conclusion We identified proteins reflecting renal function, extracellular matrix remodelling, angiogenesis and inflammation to be associated with echocardiographic signs of early-stage heart failure. Focused proteomic phenomapping discriminated individuals at high risk for cardiac maladaptation in the community. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders

Psoriasis and its impact on the clinical outcome of patients with pulmonary embolism

Abstract Background Venous thromboembolism (VTE) is common and associated with high morbidity and mortality. Although chronic inflammation was not categorized as a traditional risk factor for VTE, chronic inflammation might increase the risk to develop VTE events. While studies confirmed an increased cardiovascular morbidity and mortality in psoriatic patients, data regarding the influence of psoriasis on patients' cardiovascular profile and on prognosis of patients with pulmonary embolism (PE) are sparse. Purpose We aimed to investigate the impact of psoriasis on prognosis of PE patients. Methods Hospitalized PE patients were stratified for psoriasis and the impact of psoriasis on outcome was investigated in the German nationwide inpatient sample of the years 2005–2017 (source: Research Data Center (RDC) of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005–2017, own calculations). Results Overall, 1,076,384 hospitalizations of PE patients (53.7% females, median age 72.0 [60.0–80.0] years) were recorded in Germany 2005–2017. Among these, 3,145 patients were additionally coded with psoriasis (0.3%). Psoriatic PE patients were younger (68.0 [57.0–76.0] vs. 72.0 [60.0–80.0] years, P&amp;lt;0.001) and more often male (64.1% vs. 46.3%, P&amp;lt;0.001). The prevalence of VTE risk factors, traditional cardiovascular risk factors and cardiovascular comorbidities was higher in psoriatic than in non-psoriatic individuals: All investigated traditional cardiovascular risk factors such as essential arterial hypertension (49.8% vs. 43.1%, P&amp;lt;0.001), diabetes mellitus (24.4% vs. 18.7%, P&amp;lt;0.001), hyperlipidaemia (14.1% vs. 12.0%, P&amp;lt;0.001), as well as obesity (19.6% vs. 9.6%, P&amp;lt;0.001) and atherosclerotic comorbidities like coronary artery disease (15.2% vs. 13.8%, P=0.022) and peripheral artery disease (3.6% vs. 2.9%, P=0.010) were more prevalent in PE patients with psoriasis. Psoriatic PE patients showed a lower in-hospital case-fatality rate (11.1% vs. 16.0%, P&amp;lt;0.001), confirmed by logistic regressions showing an independent association of psoriasis with reduced case-fatality rate (OR 0.73 [95% CI 0.65–0.82], P&amp;lt;0.001), despite higher prevalence of pneumonia (24.8% vs. 23.2%, P=0.029). Psoriasis was an independent predictor for gastro-intestinal bleeding (OR 1.35 [95% CI 1.04–1.75], P=0.023) and transfusion of blood constituents (OR 1.23 [95% CI 1.11–1.36], P&amp;lt;0.001). Conclusions Overall, only a minority (0.3%) of all PE cases were coded additionally with psoriasis. PE patients with psoriasis were hospitalized in median four years earlier than those without. Although psoriasis was associated with an unfavorable cardiovascular-risk and VTE-risk profile in PE patients, our data demonstrate a lower in-hospital mortality rate in psoriatic PE, which might be mainly driven by younger age. Our findings may improve the clinical management of these patients and contribute evidence for relevant systemic manifestation of psoriasis. Funding Acknowledgement Type of funding sources: None.

Correlation between Peri-Coronary Epicardial Adipose Tissue Volume, Cardiac Calcification and the Severity of Coronary Artery Disease by Multi Slice Computed Tomography

ABSTRACT The authors in that article addressed a very important and relevant issue. Background Epicardial adipose tissue (EAT) is a complex endocrine organ that plays an important role in the development of unfavorable metabolic and cardiovascular risk profile. EAT may express a variety of inflammatory mediators which may contribute to the pathogenesis of coronary artery disease (CAD). Aortic and mitral valve calcification may reflect generalized atherosclerosis in the elderly and may be a marker of high prevalence and severity of CAD. There is a direct correlation (extent, severity and the future CV events) between the coronary artery calcium and the CAD. Aim and Objectives To correlate peri-coronary epicardial adipose tissue and coronary artery calcification and valvular (aortic and mitral) calcification with the severity of the coronary artery disease. Patients and Methods The study recruited 200 patients with suspected coronary artery disease. The amount of EAT surrounding the left main and the three main coronary arteries was quantified in axial cuts with the most distinct layer of EAT. The amount of calcium in the aortic and mitral valve and the coronaries were quantified with multi-detector computed tomography MDCT using dedicated software for measuring calcium score that is based on Agatson score. Coronary artery disease severity was assessed in terms of number of vessels affected and the severity of coronary stenosis by multi-planner reformation technique. Results Based on the finding of the MDCT and according to the presence of calcification in the aortic or the mitral valves, and the significance of the coronary artery disease, patients were classified into two groups, group (I): 115 patients with normal coronaries or with non significant lesions in their coronaries, and group (II): 85 patients with significant coronary artery disease. The Mean ± SD (in millimeters) of EAT for the entire study cohort in various coronary artery locations were as follows: LM EAT 9.82 ± 2.67, proximal LAD EAT 10.06 ± 2.80, mid LAD EAT 9.15 ± 2.41, distal LAD EAT 6.46 ± 1.87, proximal LCX EAT 8.10 ± 1.90, distal LCX EAT 6.83 ± 1.79, proximal RCA EAT 10.23 ± 2.42, mid RCA EAT 9.26 ± 2.72, distal RCA EAT 7.25 ± 2.58. Statistically highly significant difference was observed between the two groups with regards to LM EAT, proximal, mid and distal LAD EAT, proximal and distal LCX EAT, proximal, mid and distal RCA EAT (8.38 ± 2.18 Vs 11.77 ± 1.94 P: 0.000, 8.49 ± 2.21 Vs 12.18 ± 2.00, 7.93 ± 1.77 Vs 10.81 ± 2.16, 5.45 ± 1.26 Vs 7.82 ± 1.68 P: 0.000, 7.08 ± 1.34 Vs 9.46 ± 1.67, 6.05 ± 1.50 Vs 7.89 ± 1.61 P: 0.000, 9.01 ± 1.94 Vs 11.88 ± 1.99, 8.07 ± 2.32 Vs 10.86 ± 2.39, 6.31 ± 2.26 Vs 8.51 ± 2.45 P: 0.000; respectively). Statistically highly significant difference was observed between the two groups with regards calcium score and the severity of CAD in the three major vessels (LAD, LCX and RCA) and the total calcium score in all vessels (35 (16 – 85.5) Vs 179.5 (59.5 – 243) P: 0.000, 20.5 (7 – 50.5) Vs 56 (33 – 95) P: 0.000, 31 (9 – 54) Vs 97 (54 – 199) P: 0.000, 12 (0 – 84) Vs 286 (106 – 511) P:0.000; respectively) while calcium score in the LM was not statistically significant with the severity of CAD (4 (3 – 26) Vs 12 (9 – 16) P: 0.360). As regards aortic valve calcification there was statistically highly significant difference between the two groups; P value 0.000, while mitral valve calcification was found to be not statistically significant between the two groups P: 0.272. Conclusion The present study demonstrated a significant correlation between the peri-coronary epicardial adipose tissue, coronary calcification and aortic valve calcification and the severity of the coronary artery disease.

Cardiovascular Risk Factor Progression in Adolescents and Young Adults With Type 2 Diabetes

Background: Onset of type 2 diabetes (T2D) in youth confers a high risk of early adverse cardiovascular outcomes. We describe the cumulative incidence of hypertension, LDL-cholesterol dyslipidemia, hypertriglyceridemia, and prevalence of smoking over time, and examine the relationships with body mass index and measures of glycemia, insulin sensitivity, and beta-cell function in an adolescent cohort with T2D enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. Methods: Longitudinal data from the TODAY clinical trial and TODAY2 observational follow-up study were used to evaluate the relationships between hypertension, LDL-C dyslipidemia, hypertriglyceridemia, and smoking with risk factors using time-to-event models and generalized estimating equation models. Findings: Data were available on 677 participants. Mean age at baseline was 14±2 years and mean follow-up 10·2±4·5 years. The 14-year cumulative incidence of hypertension, LDL-C dyslipidemia, and hypertriglyceridemia was 59%, 33%, and 37% respectively, and the average prevalence of reported smoking was 23%. Male sex, non-Hispanic white race/ethnicity, obesity, poor glycemic control, lower insulin sensitivity, and reduced beta-cell function were significantly associated with an unfavorable cardiovascular risk profile. After an average of 10·2 years of follow-up, 54% of the cohort had ≥2 cardiovascular risk factors in addition to T2D. Interpretation: Cardiovascular risk factor incidence and prevalence was high over a decade of follow-up in young adults with youth-onset T2D. Addressing glucose control and insulin sensitivity, as well as medical management of cardiovascular risk factors will be critical in youth with T2D for prevention of cardiovascular morbidity and mortality. Trial Registration: Clinicaltrials.gov NCT00081328. Funding: United States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease. Declaration of Interest: None of the authors reported a conflict of interest. Ethical Approval: The TODAY and TODAY2 studies were approved by institutional review boards at all 15 centers and all participants and guardians provided written informed assent and/or consent as appropriate for age.

Proteomic profiling for detection of early-stage heart failure in the community.

AimsBiomarkers may provide insights into molecular mechanisms underlying heart remodelling and dysfunction. Using a targeted proteomic approach, we aimed to identify circulating biomarkers associated with early stages of heart failure.Methods and resultsA total of 575 community‐based participants (mean age, 57 years; 51.7% women) underwent echocardiography and proteomic profiling (CVD II panel, Olink Proteomics). We applied partial least squares‐discriminant analysis (PLS‐DA) and a machine learning algorithm [eXtreme Gradient Boosting (XGBoost)] to identify key proteins associated with echocardiographic abnormalities. We used Gaussian mixture modelling for unbiased clustering to construct phenogroups based on influential proteins in PLS‐DA and XGBoost. Of 87 proteins, 13 were important in PLS‐DA and XGBoost modelling for detection of left ventricular remodelling, left ventricular diastolic dysfunction, and/or left atrial reservoir dysfunction: placental growth factor, kidney injury molecule‐1, prostasin, angiotensin‐converting enzyme‐2, galectin‐9, cathepsin L1, matrix metalloproteinase‐7, tumour necrosis factor receptor superfamily members 10A, 10B, and 11A, interleukins 6 and 16, and α1‐microglobulin/bikunin precursor. Based on these proteins, the clustering algorithm divided the cohort into two distinct phenogroups, with each cluster grouping individuals with a similar protein profile. Participants belonging to the second cluster (n = 118) were characterized by an unfavourable cardiovascular risk profile and adverse cardiac structure and function. The adjusted risk of presenting echocardiographic abnormalities was higher in this phenogroup than in the other (P < 0.0001).ConclusionsWe identified proteins related to renal function, extracellular matrix remodelling, angiogenesis, and inflammation to be associated with echocardiographic signs of early‐stage heart failure. Proteomic phenomapping discriminated individuals at high risk for cardiac remodelling and dysfunction.

The Value of 4D Speckle-Tracking Strain Echocardiography in Evaluating the Relationship Between Asprosin and Growth Differentiation Factor-15 Levels and Subclinical Systolic Dysfunction in Patients With Acromegaly and Prolactinoma

Introduction: In patients with acromegaly and prolactinoma, the long-term presence of elevated GH and PRL levels is associated with an unfavorable cardiovascular risk profile. Early recognition of dysfunctions related to cardiovascular complications, which can be a significant contributor to mortality, is important. The aim of this study was to assess the relationship of four-dimensional speckle-tracking strain echocardiographic (4DSTE) measurements with asprosin, GDF-15 levels, and the Framingham cardiovascular risk score (FRS) in patients with acromegaly and prolactinoma. Methods: The study included 41 acromegaly [20F/21M, age: 49 (41-57)], 29 prolactinoma patients [18F/11M, age: 40 (28-48)] and 33 healthy control subjects [15F/18M, age: 48 (37-54)]. Data are presented as median with interquartile ranges (IQR). Anthropometric, biochemical and echocardiographic measurements were performed. Asprosin and GDF-15 levels were measured by ELISA. Results: Plasma asprosin concentration in the prolactinoma group [2.4 ng/mL (0.0-9.7)] was significantly lower than the concentration in both the acromegaly group [6.8 ng/mL (2.6-9.9)] and the control group [10.2 ng/mL (2.3-18.0)] (p=0.022 and p=0.006, respectively). In the study population, asprosin levels were positively correlated with age, FRS, and GDF-15 levels (r=0.361, p<0.001; r=0.275, p=0.005 and r=0.240, p=0.015; respectively). Plasma GDF-15 concentration was lower in prolactinoma group [262.2 pg/mL (169.3-336.1)] than in the acromegaly [332.5 pg/mL (257.4-438.8)] and control groups [331.3 pg/mL (233.6-428.9)] (p=0.008 and p=0.047, respectively). In multiple linear regression analysis, GDF-15 level was independently positively related to the FRS in both patient groups (p<0.001). FRS was highest in patients with acromegaly (p=0.004). In 2DE; the left ventricular ejection fraction although within normal limits, was lower in acromegaly [63% (63-65)] and prolactinoma [63% (60-65)] patients compared to the healthy controls [66% (63-68)] (p=0.003). In both acromegaly and prolactinoma groups; global longitudinal, circumferential, areal and radial strain measurements identified by 4DSTE were lower than the control group (acromegaly: p=0.007, p=0.008, p=0.015, p=0.008; prolactinoma: p=0.033, p=0.019, p=0.030, p=0.025, respectively). In contrast, diastolic functions were evaluated as normal in 85% of acromegaly patients, 86% of prolactinoma patients, and 93% of the control group (p=0.365). Conclusion: This is the first study to demonstrate the isolated subclinical systolic dysfunction identified by four-dimensional echocardiography in patients with acromegaly and prolactinoma. Asprosin may be associated with cardiovascular diseases in addition to its role in the pathogenesis of type 2 diabetes mellitus, and GDF-15 can be used as a biomarker to predict cardiovascular risk in these patient groups.