Determinants Of Cardiovascular Disease Research Articles

Cohort profile of a prospective cohort study among middle-aged community-dwellers in rural Vietnam: The Khánh Hòa cardiovascular study.

Disease burden associated with cardiovascular diseases (CVDs) in low- and middle-income countries has been on an increasing trend in the past decades. Despite the worldwide genetic, cultural, and environmental variations in determinants of CVDs, few studies have attempted the identification of risk factors of CVDs in low- and middle-income countries. This article aims to introduce the Khánh Hòa Cardiovascular Study, a prospective cohort study among middle-aged community dwellers in rural Khánh Hòa, Vietnam. A total of 3000 individuals, aged 40-60 years at baseline, participated in the baseline survey conducted from June 2019 to June 2020 and will be followed up for the subsequent 10 years. The baseline survey collected information on sociodemographic variables, disease history, lifestyle, social environment, and mental health via questionnaires, physical examinations, and biochemical measurements. Information on the incidence of severe health outcomes (i.e., mortality, CVDs, and cancer) has been and will be collected using a study-specific disease registry. Results showed that the prevalences of excess body weight (body mass index ≥25 kg/m2), hypertension, diabetes mellitus, and dyslipidemia were 25.9%, 39.6%, 10.2%, and 45.1%, respectively. Furthermore, by March 2023, 21 participants had died, including 5 CVD deaths and 12 cancer deaths. Moreover, we recorded 22 and 31 cases of nonfatal CVDs and cancer, respectively. These results suggest that many rural residents in Vietnam have high cardiometabolic risk, and underscore the importance of advancing research to identify risk factors and prevent the onset of serious health events.

Relationship between personal anxiety and genes associated with eating disorders in women aged 45-64

Aim. To study the possible relationship between personal anxiety and polymorphic variants of genes associated with eating disorders (rs17782313 MC4R, rs1800497 DRD2, rs9939609 FTO) in women aged 45-64 in Novosibirsk.Material and methods. A random representative sample of women aged 45-64 years (n=1074, mean age, 54,27±0,2 years) was examined in 2003-2005 at the Research Institute of Internal and Preventive Medicine, a branch of the Institute of Cytology and Genetics, within the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) project. Personal anxiety was assessed using the Spielberger self-assessment questionnaire included in the protocol of the Multinational Monitoring of Trends and Determinants of Cardiovascular Disease — Optional Psychosocial Study (MONICA-MOPSY), tested at screenings of the World Health Organization (WHO) MONICA program in 1983-1995. The sample for the HAPIEE program was formed at the program data processing center in Prague for each of the collaborating centers in such a way that each respondent was random. From the sample, every second woman (n=537) was selected for genotyping of the FTO rs9939609 variant (n=384); every third woman (n=358) — for genotyping the MC4R rs17782313 (n=279) and DRD2 rs1800497 variants (n=327). Genotyping was performed in the laboratory of molecular genetic studies by the polymerase chain reaction with the analysis of restriction fragment length polymorphism.Results. Among women aged 45-64, anxiety was detected in 58,3%, and in 15,9% of women the anxiety level was high. The homozygous genotype C/C rs17782313 of the MC4R gene was more common among women with high anxiety levels (17,5%) than among women with low and moderate anxiety levels (1,8 and 0,8%, respectively; p=0,001). There were no significant differences in the detection rate of the rs1800497 genotypes of the DRD2 gene among women with different levels of anxiety (p>0,05). The frequency of the A/A rs9939609 genotype of the FTO gene was highest among women with high anxiety levels — 29,5%, compared to participants with low and moderate anxiety levels (15 and 15,3%, respectively; p=0,048). The probability of anxiety among carriers of the C/C+C/T genotypes of the MC4R gene was 1,29 times higher than among carriers of the T/T genotype (p=0,001). Among carriers of the A/A rs9939609 genotype of the FTO gene, the anxiety probability was 2,34 times higher than among carriers of the A/T+T/T genotypes (p=0,008).Conclusion. The association between anxiety and genes of eating disorders dictates the need for diagnosis and subsequent treatment of anxiety and its associated consequences.

Bayesian spatial-temporal analysis and determinants of cardiovascular diseases in Tanzania mainland

BackgroundCardiovascular Diseases (CVDs) are health-threatening conditions that account for high mortality in the world. Approximately 23.6 million deaths due to CVD is expected in the year 2030 worldwide. The CVD burden is more severe in developing countries, including Tanzania.ObjectivesThis study analyzed the spatial-temporal trends and determinants of cardiovascular diseases in Tanzania from 2010 to 2019.MethodsIndividual data were extracted from Jakaya Kikwete Cardiac Institute (JKCI), Mbeya Zonal Referral Hospital (MZRH), Kilimanjaro Christian Medical Centre (KCMC) and Bugando hospitals and the geographical data from TMA. The model containing spatial and temporal components was analyzed using the Bayesian hierarchical method implemented using Integrated Nested Laplace Approximation (INLA).ResultsThe results found that the incidence of CVD increased from 2010 to 2014 and decreased from 2015 to 2019. The southern highlands, lake, central and coastal zones were more likely to have CVD problems than others. It was also revealed that people aged 60–64 years OR = 1.49, females OR = 1.51, smokers OR = 1.76, alcohol drinkers OR = 1.48, and overweight OR = 1.89 were more likely to have CVD problems. Additionally, a 1oC increase in the average annual air maximum temperature was related to a 14% risk of developing CVD problems. The study revealed that the model, which included spatial and temporal random effects, was the best-predicting model.ConclusionThe study shows a decreased CVD incidence rate from 2015 to 2019. The CVD incidences occurred more in Tanzania’s coastal and lake areas between 2010 and 2019. The demographic, lifestyle and geographical risk factors were significantly associated with the CVD.

Difference in risk factor profile for abdominal aortic aneurysm and thoracic aortic aneurysm

ObjectivePrevious studies suggest partly different risk factor profiles of thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs), but prospective data are scarce. The purpose of this prospective population-based case-control study was to investigate differences in risk factor profile between TAAs and AAAs. MethodsParticipants in two prospective population-based studies, the Västerbotten Intervention Project (VIP) and the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, between 1986 and 2010, underwent cardiovascular risk assessments, including blood samples, oral glucose tolerance test, blood pressure readings, and a self-reported health questionnaire. All individuals who were later diagnosed with TAAs or AAAs were identified. Age, sex, and time-matched controls were selected from the same cohorts, aiming at four controls/case. Adjusted odds ratios (aORs) for potential risk factors for later diagnosis of TAAs and AAAs, respectively, were estimated by multivariate conditional logistic regression analyses. ResultsFrom a total of 96,196 individuals with prospectively collected data in the VIP/MONICA cohort, a total of 236 individuals with AAAs (181 men and 55 women) and 935 matched controls, and 168 individuals with TAAs (115 men and 53 women) and 662 controls were included. The average age at baseline examination was 57.0 ± 5.7 years for AAA cases and controls, and 52.1 ± 8.8 years for TAA cases and controls. Mean time between baseline examination and diagnosis of AAAs/TAAs was 12.1 and 11.7 years, respectively. There was a clear difference in risk factor profile between AAAs and TAAs. Smoking, hypertension, and coronary artery disease were significantly associated with later diagnosis of AAAs, with highest aORs for a history of smoking (aOR, 10.3; 95% confidence interval [CI], 6.3-16.8). For TAAs, hypertension was the only positive risk factor (aOR, 1.7; 95% CI, 1.1-2.7), whereas smoking was not associated. Diabetes was not associated with either AAAs or TAAs; neither was self-reported physical activity. ConclusionsIn this prospective, population-based, case-control study, risk factor profile differed between AAAs and TAAs. This suggests a partially different etiology for TAAs and AAAs.

The Impact of Organized Exercise and Non-organized Leisured Time Activity on Serum Pentraxin3 and C-reactive Protein Levels, Lipid Profile and Physical Fitness in Diabetic Children

Background: Microvascular changes and precursors of atherosclerosis are frequently observed in young patients with early-onset type 1 diabetes (T1DM). Due to their known beneficial effects, physical activity is strongly recommended for its management. Objectives: This study aimed to investigate the effects of eight weeks of organized exercise (OE) and non-organized leisure time activity (NOLTA) on determinants of cardiovascular disease and physical fitness in children with type 1 diabetes. Methods: In this quasi-experimental study, 20 children with T1DM were randomly divided into two groups of 10: OE (n = 10, mean age = 12.60 ± 1.34 years) and NOLTA (n = 10, mean age = 12.40 ± 0.84 years). Subjects in both groups participated in their respective activities 3 days per week. Blood samples and physiological measurements were taken 48 hours before and after the 8-week training period. Results: High-density lipoprotein (HDL) levels and physical fitness factors increased significantly in both exercise groups. Fasting blood glucose, C-reactive protein, and the cholesterol/HDL ratio were also significantly reduced in both groups. Waist circumference, glycosylated hemoglobin, and the LDL/HDL ratio were significantly reduced only in the OE group. However, the decrease in the acute phase protein pentraxin 3 was minimal and statistically insignificant. Conclusions: In children and adolescents with T1DM, regular exercise—due to its anti-inflammatory effects and its ability to improve cardiorespiratory fitness, lipid profile, and blood glucose levels—may help reduce the severity and likelihood of cardiovascular disease in adulthood.

Association between the COVID-19 pandemic and mental health in very old people in Sweden.

During the COVID-19 pandemic, Sweden implemented social distancing measures to reduce infection rates. However, the recommendation meant to protect individuals particularly at risk may have had negative consequences. The aim of this study was to investigate the impact of the COVID-19 pandemic on very old Swedish peoples' mental health and factors associated with a decline in mental health. We conducted a cross-sectional study among previous participants of the SilverMONICA (MONItoring of Trends and Determinants of CArdiovascular disease) study. Of 394 eligible participants, 257 (65.2%) agreed to participate. Of these, 250 individuals reported mental health impact from COVID-19. Structured telephone interviews were carried out during the spring of 2021. Data were analysed using the χ2 test, t-test, and binary logistic regression. Of 250 individuals (mean age: 85.5 ± 3.3 years, 54.0% women), 75 (30.0%) reported a negative impact on mental health, while 175 (70.0%) reported either a positive impact (n = 4) or no impact at all (n = 171). In the binary logistic regression model, factors associated with a decline in mental health included loneliness (odds ratio [95% confidence interval]) (3.87 [1.83-8.17]) and difficulty adhering to social distancing recommendations (5.10 [1.92-13.53]). High morale was associated with positive or no impact on mental health (0.37 [0.17-0.82]). A high percentage of very old people reported a negative impact on mental health from the COVID-19 pandemic, primarily from loneliness and difficulty adhering to social distancing measures, while high morale seemed to be a protective factor.

Clustering of vascular aging manifestations and incident cardiovascular events. The Paris Prospective Study III

Abstract Background Vascular aging is a key contributor to cardiovascular disease (CVD). Manifestations of vascular aging are heterogeneous and include atherosclerosis, arterial stiffening, increased arterial wall stress and arterial diameter enlargement. These manifestations have different pathophysiological mechanisms and likely require different prevention strategies. How the different vascular aging manifestations co-exist, or cluster, at the individual level and the association of any such clusters with incident CVD is unknown. Purpose To examine how vascular aging manifestations cluster and whether any such clusters are associated with incident CVD. Methods In the Paris Prospective Study III, a French community-based prospective study on novel determinants of CVD, 10,157 participants underwent a high-resolution carotid echotracking (Artlab, Esaote) between 2008 and 2012, and were thereafter monitored every two years for CVD events up to end 2020 . Hospitalized stroke and coronary heart disease (CHD) events were validated after the review of all medical records. Hierarchical clustering analysis was employed to identify patterns of vascular aging. Hazard ratios (HRs) were quantified in Cox models. Results The study sample included 8,360 participants (39% women, mean age 59.6 years) without prevalent CVD. Three clusters of vascular aging manifestations were identified: - Cluster 1 included 3,995 (47.8%) participants and was characterized by low prevalence of carotid plaques, low carotid intima-media thickness (IMT), low carotid artery stiffness, small carotid diameter and low carotid circumferential wall stress (healthy vascular aging cluster). - Cluster 2 included 2,109 (25.2%) participants and was characterized by high carotid artery stiffness and high carotid circumferential wall stress (arterial stiffness vascular aging cluster). - Cluster 3 included 2,256 (27.0%) participants, and was characterized by high prevalence of carotid plaques and high carotid IMT(atherosclerosis vascular aging cluster). After a median follow-up of 8.5 years, 108 incident stroke events, 218 CHD events and 192 deaths occurred. Compared with cluster 1, cluster 2 (HR 1.76, [95%CI, 1.06-2.94]), but not cluster 3 (HR 1.57, [0.94-2.62]), was associated with a higher risk of stroke. In addition, compared to cluster 1, cluster 3 (HR 1.53, [1.08-2.16]), but not cluster 2 (HR 1.38, [95% CI, 0.96-1.98]), was associated with higher risk of CHD. Both cluster 2 and 3 were associated with higher all-cause mortality (HR for cluster 2: 1.50, [1.02-2.21]; HR for cluster 3: 1.48, [1.01-2.17]). Internal validation using bootstrapping methods (n=1000 samples) provided consistent findings. Conclusion The simultaneous analysis of carotid-echotracking vascular aging parameters identified three patterns of vascular aging that are differentially associated with CHD and stroke in the community.Carotid properties by clustersKM survival curves by clusters

Autoimmune Disease in Turner Syndrome in Sweden: An up to 25 Years' Controlled Follow-up Study.

Turner syndrome (TS) is the most common chromosomal aberration in women; it is the result of structural or numeric abnormalities in the X chromosome. Autoimmune hypothyroidism has been recognized as one of the more prominent disorders associated with TS. This work aimed to study the prevalence of autoimmune diseases in TS. A cross-sectional, longitudinal, 25-year follow-up study was conducted of patients from adult Turner centers at the University Hospitals, Sweden. During 1994 to 2020, a total of 503 women aged 16 to 71 years with TS were evaluated consecutively every fifth year according to national guidelines. A random population sample of women, n = 401, aged 25 to 44 years, from the World Health Organization Monitoring of Trends and Determinants for Cardiovascular Disease (MONICA) project served as controls. Serum thyrotropin, free thyroxine, vitamin B12, antithyroid peroxidase (anti-TPO), and antitransglutaminase antibodies were measured. Mean follow-up time (years) was 16 ± 7 for patients and 13 ± 1 for controls. From study start, the prevalence increased in TS for hypothyroidism 40% to 58%, vitamin B12 deficiency 5% to 12%, celiac disease 4% to 7%, positive anti-TPO 26% to 41%, and antitransglutaminase antibodies 6% to 8% (P < .0001 vs controls). Type 1 diabetes and Addison disease were rare. The only interrelationship was between hypothyroidism and vitamin B12 deficiency, both in TS and controls. No association between autoimmune disease and karyotype, antecedent growth hormone treatment, or ongoing estrogen hormone replacement, was seen in TS. In women with TS up to older than 80 years, more than half developed hypothyroidism, mainly autoimmune, during follow-up. Awareness of vitamin B12 deficiency and celiac disease throughout life is also recommended in women with TS.

Dietary habits among snus users: a population-based cross-sectional study.

The dietary habits among snus users are largely unknown and have not been accounted for in observational studies on the health effects of snus use. To examine whether snus users eat unhealthier than never tobacco users. A total of 3,397 male participants, examined between 1994 and 2014 in the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, were included. Snus use and dietary habits were self-reported using questionnaires, from which intakes of different food groups, macronutrients, and a healthy diet score (HDS) were calculated (the latter as a proxy for overall diet quality). The association between snus use and dietary habits was examined by quantile regression models. In the multivariable-adjusted model, current snus users had a lower HDS (median difference: -0.86 [95% confidence interval: -1.32, -0.40]) than never tobacco users. Snus users also consumed fewer weekly servings of fruits and berries (median difference: -1.03 [-1.65, -0.40]), and their estimated percentage of energy intake consisted of less carbohydrates (median difference: -1.43 [-2.12, -0.74]) and of more total fat (median difference: 0.99 [0.30, 1.67]), saturated fat (median difference: 0.67 [0.29, 1.05]), monounsaturated fat (median difference: 0.44 [0.20, 0.68]), trans fat (median difference: 0.03 [0.01, 0.06]), and alcohol (median difference: 0.21 [0.02, 0.40]). We observed that snus users had an unhealthier diet than never tobacco users. Future studies on the association between snus use and health outcomes should, therefore, consider diet as a potential confounder.

Trends in renal function in Northern Sweden 1986–2014: data from the seven cross-sectional surveys within the Northern Sweden MONICA study

ObjectiveThe prevalence of chronic kidney disease (CKD) is increasing globally, and CKD is closely related to cardiovascular disease (CVD). CKD and CVD share several risk factors (RF), such as diabetes,...

Determinants of cardiovascular diseases among Indian expatriates residing in Ajman, UAE-A Pilot study

Determinants of cardiovascular diseases among Indian expatriates residing in Ajman, UAE-A Pilot study

Eating speed and abdominal adiposity in middle-aged adults: a cross-sectional study in Vietnam

BackgroundSeveral studies have associated fast eating speed with the risk of general obesity, but there are inadequate data on the association between eating speed and abdominal adiposity which may pose a higher threat to health than general obesity. The present study aimed to investigate the association between eating speed and abdominal obesity in a Vietnamese population.MethodsBetween June 2019 and June 2020, the baseline survey of an ongoing prospective cohort study on the determinants of cardiovascular disease in Vietnamese adults was conducted. A total of 3,000 people aged 40–60 years old (1,160 men and 1,840 women) were recruited from eight communes in the rural district of Cam Lam, Khanh Hoa province, in Central Vietnam. Self-reported eating speed was assessed on a 5-point Likert scale, and responses were collapsed into the following three categories: slow, normal, and fast. Abdominal obesity was defined as a waist-to-height ratio of ≥ 0.5. Poisson regression with a robust variance estimator was used to assess the association between eating speed and abdominal obesity.ResultsCompared with slow eating speed, the adjusted prevalence ratio (95% confidence interval) for abdominal obesity was 1.14 (1.05, 1.25)1.14 (1.05, 1.25) for normal eating speed and 1.30 (1.19, 1.41) for fast eating speed (P for trend < 0.001).ConclusionA faster eating speed was associated with a higher prevalence of abdominal obesity in a middle-aged population in rural Vietnam.

The impact of a patient's social network on emergency surgery for colon cancer.

The aim of this study was to investigate if patients with a weak social network and colon cancer are more likely to be operated as an emergency than those with a strong social network. Data from patients living in Västerbotten County, Sweden, who underwent colon cancer surgery between 2007 and 2020 were extracted from the Swedish Colorectal Cancer Registry (SCRCR). Patients identified were matched against the Västerbotten Intervention Program (VIP) and the longitudinal study Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA). These two databases include a survey that includes questions regarding quality and size of the patient's social network. Multivariable logistic regression was used for analysis. Six items from the questions on social network, and the composite variables availability of social integration (AVSI) and availability of attachment (AVAT) were analysed. Data from 801 patients were analysed. The odds ratio for emergency surgery was significantly higher for divorced patients (OR 2.01 (CI 1.03-3.91)) and for male gender (OR 1.51 (CI 1.02-2.24)). A higher OR was seen amongst those with no-one to share feelings with (OR 1.57 (CI 0.82-3.03)) or to comfort them (OR1.33 (CI 0.78-2.28)). Quantitative aspects of social life such as the number of people greater than 10 that feel relaxed at the patient's home, showed a lower OR (OR 0.71(CI 0.35-1.43)). The impact of social network on the risk for emergency surgery for colon cancer is limited. Divorced status and male gender were associated with an increased risk for emergency surgery.

About Some Social Characteristics of Chronic Stress of Shift Workers in the Arctic Conditions

The expeditionary-shift method of organizing labor involves an increase in the intensity of labor during the shift, a longer work shift, a decrease in inter-shift rest in the absence of days off and minimal social and domestic security. The article is devoted to the study of the parameters of stress at work and in the family among men aged 25-54, employed in expeditionary-shift work in the Arctic territories of the Tyumen region. A sociological study was conducted on an organized population of men aged 25-54, employed in expeditionary-shift work for more than five years at one of the industrial enterprises of the Tyumen region. The comparison group consisted of an organized population of men in the same age range, working permanently in the city of Tyumen. Determination of stress at work and stress in the family was carried out according to the WHO standard questionnaire MONICA-psychosocial (Multinational Monitoring of Trends and Determinants of Cardiovascular Disease - Optional Psychosocial Sybstudy). Among the men employed in the expeditionary-shift form of work, most often over the previous period of twelve months, a change in specialty was established, an increase in the load and responsibility at the workplace, a more negative attitude towards work, an increase in conflicts with subordinates, but also the possibility of rest after working day while reducing "other" changes at work. According to the parameters of stress in the family, among men employed in expeditionary-shift work, over the previous period of twelve months, a change in marital status, an increase in conflicts in the family, but also opportunities for a relaxing home rest were most often determined. Thus, the obtained results of a sociological study, which determined a significantly higher prevalence of some factors of chronic social stress after five years of work in the Arctic territories of the Tyumen region, should become a scientific basis for the formation of a socially oriented preventive program to reduce the risks of developing CVD among workers in the oil and gas production complex employed in expeditionary - shift form of work.

JS-ECCR/HBPRCA-2: HOMOCYSTEINE AND LIPOPROTEIN (A) AS A DETERMINANT OF ARTERIAL STIFFNESS AND A PREDICTOR OF HYPERTENSION MEDIATED TARGET ORGAN DAMAGE (HMOD)

Background: Despite advances in modern medicine, cardiovascular disease (CVD) remains a leading cause of global mortality. Among the many CVD determinants, hypertension is a leading modifiable risk factor and blood pressure control and prevention of hypertension mediated target organ damage (HMOD) has become the hallmark of cardiovascular risk management. Homocysteine and lipoprotein (a) are independent CVD risk factors, proposed to contribute to vascular compromise by facilitating thrombogenesis and atherosclerosis. Aims: We sought to determine in a real-world clinical setting whether these risk factors interact to facilitate vascular organ damage in hypertension. Methods: We performed a cross-sectional analysis of prospectively collected data in 131 hypertensive patients referred to our tertiary hypertension clinic at Royal Perth Hospital. The Lipoprotein (a), homocysteine and other biochemical parameters studied were assayed in the central hospital laboratory. We analysed the effect of the interaction between Lipoprotein (a) and homocysteine (Lpa-Hcy) on markers of HMOD including arterial stiffness, as assessed by pulse wave velocity (PWV). Results: The average age of participants was 56 ± 0.9 years, and there was a greater proportion of males than females (62% vs. 38%). The regression analysis demonstrated that Lp(a)-Hcy interaction was significantly associated with PWV [beta = 0.33; 95% CI 0.12, 0.55; p &lt; 0.005], 24 h urinary protein excretion [beta = -10.9; 95% CI -14.5, -7.4; p &lt; 0 .001], and estimated glomerular filtration rate [beta = 103.9; 95% CI 93.9, 113.8; p &lt; 0.001], which persisted after adjusting for potential confounders such as age, sex, 24 h BP, inflammation, smoking, diabetes mellitus and other metabolic risk factors. Interaction analysis showed that increasing homocysteine and lipoprotein (a) concentration was associated with increasing arterial stiffness. Hcy levels does not affect the PWV if Lp(a) levels are normal and the knowledge of both Lp(a) and Hcy are necessary to determine arterial damage. Furthermore, Lp(a)-Hcy product exhibited a positive predictive relationship with every unit increase in Lp(a)-Hcy product associated with a 0.3 m/s increase in PWV which may represent a useful marker for cardiovascular risk stratification and may suggest the need for rigorous treatment to minimise HMOD progression. These clinical findings provide novel insights into the potential interaction between Lp(a) and Hcy in the pathogenesis of hypertension mediated vascular damage

The Association of Social Connectivity and Body Weight With the Onset of Type 2 Diabetes: Findings From the Population-Based Prospective MONICA/KORA Cohort.

Low levels of social connectivity are related to the onset of type 2 diabetes mellitus (T2D), and this study investigates the role of body weight in this association. In a sample of 9448 participants followed for a mean of 15.3 years (186,158.5 person-years) from the Monitoring of Trends and Determinants in Cardiovascular Disease Augsburg/Cooperative Health Research in the Region of Augsburg population-based cohort conducted in Germany, we investigated the association of social connectivity, measured by the Social Network Index, and body mass index (BMI) with the risk of clinically validated T2D incidence using stratified Cox proportional hazards regression models adjusted for sociodemographic, life-style, cardiometabolic, and psychosocial risk factors. During a mean follow-up of 14.1 years (186,158.5 person-years), 975 (10.3%) participants developed T2D. Participants with low social connectivity developed T2D at a higher rate than socially connected participants (10.0 versus 8.0 cases/10,000 person-years); however, BMI played a significant role in the association of social connectivity with T2D ( p < .001). In comparison to their socially connected counterparts, low social connectivity was associated with a higher rate of T2D incidence in normal-weight (6.0 versus 2.0 cases/10,000 person-years), but not overweight (13.0 versus 13.0 cases/10,000 person-years) or obese participants (32.0 versus 30.0 cases/10,000 person-years). Correspondingly, Cox regression analysis showed that 5-unit increments in BMI increased the risk of T2D in socially connected participants (hazard ratio = 3.03, 95% confidence interval = 2.48-3.79, p < .001) at a substantially higher rate than in low socially connected participants (hazard ratio = 1.77, 95% confidence interval = 1.45-2.16, p < .001). The detrimental link between low social connectivity and increased risk of T2D is substantially stronger in participants with a lower BMI.

Extracellular nucleophosmin is upregulated in psoriasis and correlates with determinants of cardiovascular diseases

Abstract Introduction We previously showed that genotoxic stress induced an active extracellular release of nucleophosmin (NPM) in human cardiac mesenchymal progenitor cells, and that serum deprivation provokes NPM secretion from human endothelial cells, eliciting inflammation via nuclear factor kappa B (NF-kB) transcriptional activation. Purpose The aim of this study was to determine whether NPM was modulated in skin and plasma of psoriatic patients (Pso). Methods 29 Pso were compared to 29 control subjects (Ctrl) age- and sex-matched. All Pso had a severe psoriasis, defined as Psoriasis Area and Severity Index (PASI) &amp;gt;10 and one of the following: at least two systemic psoriasis treatments, psoriasis onset &amp;lt;40 years of age, disease duration &amp;gt;10 years. Exclusion criteria were: diabetes, cardiovascular events, psoriatic arthritis. Total RNA was extracted from plasma and miR-200c levels assayed by quantitative real-time PCR. NPM levels were assayed by ELISA. The clinical parameters were similar between the two groups except for Total Cholesterol (mg/dl) (Ctrl 193.3±6.2; Pso 213.2±6.9; P&amp;lt;0.05). Blood pressure measurement, wave reflection analysis and pulse wave velocity (PWV) were similar between groups, echocardiographic parameters were different for left ventricular (LV) mass index (g/m2) (Ctrl 84.2±5.2; Pso 102.5±4.7; P&amp;lt;0.05) and relative wall thickness (RWT) (Ctrl 0.4±0.0; Pso 0.48±0.0; P&amp;lt;0.01). Total RNA was extracted from biopsies of nonlesional (NLS) and lesional (LS) of 6 Pso and 6 healthy subject skin (HS) from which human fibroblasts (HFs) and primary Keratinocytes (KCs) were extracted. Results NPM was upregulated in LS (1.9+0.3 fold; p=0.05) vs NLS biopsies (2.9+0.1 fold; p&amp;lt;0.01) and was also increased at the transcriptional level in LS vs NLS (8.6+ 1.7fold; p&amp;lt;0.05). Both the innate stimuli, such as lipopolysaccharides and Poly I:C and adaptive stimuli, i.e. cytokine mix, were able to induce extracellular release of NPM in immortalized KCs and HFs. Interestingly, NPM interacts with Toll like receptor (TLR)4 and activates a NF-kB-dependent inflammatory pathway upregulating interleukin IL-6 and COX-2 gene expression. Circulating NPM was increased in the plasma of 29 Pso (1.1+0.1ng/ml; p&amp;lt;0.001) compared to 29 healthy controls (0.78+ 0.03ng/ml) and positively correlates with PASI (Rs=0.44; p=0.05) and with determinants of cardiovascular diseases (CVDs), i.e. PWV (Rs=0.5; p&amp;lt;0.008), PASis (Rs= 0.4; P&amp;lt;0.05) and LV mass (Rs=0.49; p&amp;lt;0.05). Further, NPM positively correlates with miR-200c circulating levels (Rs=0.29; p&amp;lt;0.05), that we previously showed to increase in Pso and to correlate with CVD progression. We found that circulating miR-200c physically associated with NPM, that most probably is responsible for its extracellular release and protection upon cytokine mix via a TLR4-mechanism. Conclusions NPM is increased in psoriasis both in skin and in plasma and could be a novel biologic target to counteract chronic inflammation associated with CVD risk. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Italian Ministry of Health and AFM Telethon 22522 grant to AM

Race, Interleukin-6, TMPRSS6 Genotype, and Cardiovascular Disease in Patients With Chronic Kidney Disease.

Background Differences in death rate and cardiovascular disease (CVD) between Black and White patients with chronic kidney disease is attributed to sociocultural factors, comorbidities, genetics, and inflammation. Methods and Results We examined the interaction of race, plasma IL-6 (interleukin-6), and TMPRSS6 genotype as determinants of CVD and mortality in 3031 Chronic Renal Insufficiency Cohort study participants. The primary outcomes were all-cause mortality and a composite of incident myocardial infarction, peripheral artery disease, stroke, and heart failure. During the median follow-up of 10 years, Black patients with chronic kidney disease experienced a significantly higher mortality (34% versus 26%) and CVD composite (41% versus 28%) compared with White patients. After adjustment, TMPRSS6 genotype did not associate with the outcomes. The adjusted hazard ratio for mortality (4.11 [2.48-6.80], P<0.001) and CVD composite (2.52 [1.96-3.24], P<0.001) were higher for the highest versus lowest IL-6 quintile. The adjusted hazards for death per 1-quintile increase in IL-6 in White and Black individuals were 1.53 (1.42-1.64) versus 1.29 (1.20-1.38) (P<0.001), respectively. For CVD composite they were 1.61 (1.50-1.74) versus 1.30 (1.22-1.39) (P<0.001), respectively. In Cox proportional hazard models that included IL-6, there was no longer a racial disparity for death (1.01 [0.87-1.16], P=0.92), but significant unexplained mediation remained for CVD (1.24 [1.07-1.43]; P=0.004). Path models that included IL-6, diabetes, and urine albumin to creatinine ratio were able to identify variables responsible for racial disparity in mortality and CVD. Conclusions Racial differences in mortality and CVD among patients with chronic kidney disease could be explained by good-fitting path models that include selected mediator variables including diabetes and plasma IL-6.

Kidney function in patients with bipolar disorder with and without lithium treatment compared with the general population in northern Sweden: results from the LiSIE and MONICA cohorts

The clinical relevance of lithium nephropathy is subject to debate. Kidney function decreases with age and comorbidities, and this decline might lead to attribution bias when erroneously ascribed to lithium. We aimed to investigate whether patients with bipolar or schizoaffective disorder had faster decline in estimated glomerular filtration rate (eGFR) compared with the general population, whether observed differences in the steepness of the decline were attributable to lithium, and whether such changes depended on the length of lithium exposure. In this cross-sectional cohort study, we used clinical data from the Lithium-Study into Effects and Side-effects (LiSIE) retrospective cohort study, which included patients with bipolar disorder or schizoaffective disorder whose medical records were reviewed up to Dec 31, 2017, and the WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, covering a representative sample of the general population in northern Sweden aged 25-74 years. The primary outcome was the age-associated decline of creatinine-based eGFR, assessed using linear regression. We adjusted for sex and grouped for different lengths of lithium exposure (never or <1 year, 1-5 years, >5-10 years, and >10 years). For patients with moderate-to-severe kidney disease we identified the underlying nephropathy in the case records. From LiSIE, we included 785 patients (498 [63%] female and 287 [37%] male), with a mean age of 49·8 years (SD 13·2; range 25-74). From MONICA, we included 1549 individuals (800 [52%] female and 749 [48%] male), with a mean age of 51·9 years (13·8; 25-74). No ethnicity data were collected. Adjusted for duration of lithium exposure, eGFR declined by 0·57 mL/min/1·73 m2/year (95% CI 0·50-0·63) in patients with bipolar disorder or schizoaffective disorder and by 0·57 mL/min/1·73 m2/year (0·53-0·61) in the reference population. Lithium added 0·54 mL/min/1·73 m2 (0·43-0·64) per year of treatment (p<0·0001). After more than 10 years on lithium, decline was significantly steeper than in all other groups including the reference population (p<0·0001). Lithium nephropathy was judged to be the commonest cause of moderate-to-severe chronic kidney disease, but comorbidities played a role. The effect of lithium on eGFR showed a high degree of inter-individual variation. Steeper eGFR decline in patients with bipolar disorder or schizoaffective disorder can be attributed to lithium, but the trajectory of kidney function decline varies widely. Comorbidities affecting kidneys should be treated assertively as one possible means to affect the trajectory. In patients with a fast trajectory, a trade-off is required between continuing lithium to treat mental health problems and discontinuing lithium for the sake of renal health. Norrbotten County Research and Learning Fund Sweden, Visare Norr (Northern County Councils Regional Federation Fund), Swedish Kidney Foundation (Njurfonden), Swedish Kidney Association (Njurförbundet), Norrbotten section. For the Swedish translation of the Summary see Supplementary Materials section.

Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases.

We previously showed that genotoxic stress induced an active extracellular release of nucleophosmin (NPM) in human cardiac mesenchymal progenitor cells, and that serum deprivation provokes NPM secretion from human endothelial cells, eliciting inflammation via nuclear factor kappa B (NF-kB) transcriptional activation. In this study, we wanted to determine whether NPM was similarly modulated in the skin and plasma of psoriatic patients (Pso). We found that NPM was induced in 6 skin biopsies compared to 6 normal skin biopsies and was markedly increased in lesional (LS) vs. non-lesional skin (NLS) biopsies. Moreover, NPM was also increased at the transcriptional levels in LS vs. NLS. Both the innate stimuli, such as lipopolysaccharides and Poly inositol–cytosine and adaptive stimuli, that is, cytokine mix, were able to induce the extracellular release of NPM in immortalized keratinocytes and human skin fibroblasts in the absence of cytotoxicity. Interestingly, NPM interacts with Toll-like receptor (TLR)4 in these cells and activates an NF-kB-dependent inflammatory pathway upregulating interleukin IL-6 and COX-2 gene expression. Finally, circulating NPM was increased in the plasma of 29 Pso compared to 29 healthy controls, and positively correlates with psoriasis area severity index (PASI) and with determinants of cardiovascular diseases (CVDs), such as pulse wave velocity, systolic pressure, and left ventricular mass. Furthermore, NPM positively correlates with miR-200c circulating levels, which we previously showed to increase in Pso and correlate with CVD progression. Our data show that circulating miR-200c is physically associated with extracellular NPM, which most probably is responsible for its extracellular release and protection upon cytokine mix via a TLR4-mechanism. In conclusion, NPM is increased in psoriasis both in the skin and plasma and might be considered a novel biologic target to counteract chronic inflammation associated with CVD risk.