Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study.

BACKGROUND & AIMS: Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and the risk of developing IBD using the Prospective Urban Rural Epidemiology cohort. METHODS: This was a prospective cohort study of 133,137 individuals between the ages of 20 and 80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed up prospectively at least every 3 years. The main outcome was the development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aORs) with 95% CIs. RESULTS: During a median follow-up period of 11.0 years (interquartile range, 9.2-12.2 y), there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was associated significantly with baseline antibiotic (aOR, 2.81; 95% CI, 1.67-4.73; P = .0001) and hormonal medication use (aOR, 4.43; 95% CI, 1.78-11.01; P = .001). Among females, previous or current oral contraceptive use also was associated with IBD development (aOR, 2.17; 95% CI, 1.70-2.77; P < .001). Nonsteroidal anti-inflammatory drug users also were observed to have increased odds of IBD (aOR, 1.80; 95% CI, 1.23-2.64; P = .002), which was driven by long-term use (aOR, 5.58; 95% CI, 2.26-13.80; P < .001). All significant results were consistent in direction for CD and UC with low heterogeneity. CONCLUSIONS: Antibiotics, hormonal medications, oral contraceptives, and long-term nonsteroidal anti-inflammatory drug use were associated with increased odds of incident IBD after adjustment for covariates.

May Measurement Month 2019: analysis of blood pressure screening in Bishkek, Kyrgyzstan.

High blood pressure (BP) is one of the leading causes of death in Kyrgyzstan. The world's largest event in the field of increasing awareness of raised BP is the May Measurement Month (MMM) campaign. Kyrgyzstan joined MMM in 2019. The inclusion criteria for participants in the study were: age ≥18 years and providing informed consent. Hypertension was defined as the presence of systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg based on the mean of the second and third of three sitting BP measurements or on treatment for hypertension. Most of the participants (96.9%) were surveyed inside two large shopping malls of Bishkek. The total number of people who took part in the screening was 2013. The mean age was 38.8 (± 12.6) years, and 1006 were women (50.0%) and 1007 men (50.0%). One-hundred eighty-four participants had hypertension (9.1%), of whom 59 (32.0%) were aware of their diagnosis, and hypertension was controlled in 25 participants (13.7%). The mean BMI was 24.0 (± 4.1) kg/m2, 34 (1.7%) participants had diabetes mellitus, 12 (0.6%) had a history of myocardial infarction, 4 (0.2%) had a history of stroke, 314 (15.6%) were smokers. 41 (2.0%) drank alcohol 1-3 times a month, 46 (2.3%)-once per week. MMM screening allows us to gather up-to-date data on the prevalence, awareness and control of hypertension among volunteer screenees in Bishkek, Kyrgyzstan.

Reperfusion therapies and in-hospital outcomes for ST-elevation myocardial infarction in Europe: the ACVC-EAPCI EORP STEMI Registry of the European Society of Cardiology.

AIMS: The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset <24 h in 196 centres across 29 countries. A total of 11 462 patients were enrolled, for whom primary percutaneous coronary intervention (PCI) (total cohort frequency: 72.2%, country frequency range 0-100%), fibrinolysis (18.8%; 0-100%), and no reperfusion therapy (9.0%; 0-75%) were performed. Corresponding in-hospital mortality rates from any cause were 3.1%, 4.4%, and 14.1% and overall mortality was 4.4% (country range 2.5-5.9%). Achievement of quality indicators for reperfusion was reported for 92.7% (region range 84.8-97.5%) for the performance of reperfusion therapy of all patients with STEMI <12 h and 54.4% (region range 37.1-70.1%) for timely reperfusion. CONCLUSIONS: The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Statin therapy in athletes and patients performing regular intense exercise - Position paper from the International Lipid Expert Panel (ILEP).

Acute and chronic physical exercises may enhance the development of statin-related myopathy. In this context, the recent (2019) guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) for the management of dyslipidemias recommend that, although individuals with dyslipidemia should be advised to engage in regular moderate physical exercise (for at least 30 min daily), physicians should be alerted with regard to myopathy and creatine kinase (CK) elevation in statin-treated sport athletes. However it is worth emphasizing that abovementioned guidelines, previous and recent ESC/EAS consensus papers on adverse effects of statin therapy as well as other previous attempts on this issue, including the ones from the International Lipid Expert Panel (ILEP), give only general recommendations on how to manage patients requiring statin therapy on regular exercises. Therefore, these guidelines in the form of the Position Paper are the first such an attempt to summary existing, often scarce knowledge, and to present this important issue in the form of step-by-step practical recommendations. It is critically important as we might observe more and more individuals on regular exercises/athletes requiring statin therapy due to their cardiovascular risk.

The global burden of falls: global, regional and national estimates of morbidity and mortality from the Global Burden of Disease Study 2017.

BACKGROUND: Falls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) provides a comprehensive assessment of morbidity and mortality from falls. METHODS: Estimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records. RESULTS: Globally, the age-standardised incidence of falls was 2238 (1990-2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence was 5186 (4622-5849) per 100 000 in 2017, representing a decline of 6.5% (7.6 to 5.4) from 1990 to 2017. Age-standardised mortality rate was 9.2 (8.5-9.8) per 100 000 which equated to 695 771 (644 927-741 720) deaths in 2017. Globally, falls resulted in 16 688 088 (15 101 897-17 636 830) YLLs, 19 252 699 (13 725 429-26 140 433) YLDs and 35 940 787 (30 185 695-42 903 289) DALYs across all ages. The most common injury sustained by fall victims is fracture of patella, tibia or fibula, or ankle. Globally, age-specific YLD rates increased with age. CONCLUSIONS: This study shows that the burden of falls is substantial. Investing in further research, fall prevention strategies and access to care is critical.

The association of Val109Asp polymorphic marker of intelectin 1 gene with abdominal obesity in Kyrgyz population.

BACKGROUND: The aim of this study was to quantify the association of Val109Asp polymorphism of intelectin 1 (ITLN1) gene with the abdominal obesity (AO) in Kyrgyz population. METHODS: Patients admitted to annual screening at a local outpatient facility were enrolled or this study. We genotyped 297 nonrelated adults of Kyrgyz ethnicity, of whom 127 were AO patients, including 46 men and 81 women with the mean age 53.2 ± 7.1 years, and 170 non-obese controls, including 61 men and 109 women with the mean age 52.0 ± 9.0 years. AO was defined as having waist circumferences ≥ 102 cm in men and ≥ 88 cm in women. We used PCR-RFLP method to define Val109Asp polymorphism of ITLN1 gene. RESULTS: Asp109Asp, Asp109Val and Val109Val genotypes were found in 48%, 40%, and 12% of AO patients respectively, and in 53%, 43%, and 4% of controls, whereas Val109Val homozygous genotype of ITLN1 gene Val109Asp polymorphic marker was significantly more prevalent in AO patients. In Kyrgyz population, Val109Val genotype of ITLN1 gene increased the risk of AO (odds ratio (OR) 3.12, 95% CI 1.23-7.90). Asp109Asp homozygous genotype, on opposite, was not associated with this condition (OR 0.82, 95% CI 0.53-1.30). Finally, the allelic variants of Val109Asp polymorphism of ITLN1 gene were not associated with AO. CONCLUSION: Significant increase in the frequency of Val109Val genotype of ITLN1 gene in AO patients may be indicative of some potential role of ITLN1 gene in molding genetic predisposition to AO in the Kyrgyz. This requires further elaboration in the future studies.

Association between the intima-media thickness of the extracranial carotid arteries and metabolic syndrome in ethnic Kyrgyzs.

BACKGROUND: It is known that atherosclerosis is the leading cause of cardiovascular disease. We aimed to study the correlation between components of metabolic syndrome (MS) and subclinical carotid atherosclerosis in a group of ethnic Kyrgyzs. METHODS: In а descriptive study we assessed 144 ethnic Kyrgyzs (69 males, 75 females) aged 36-73 years (average age 51.03 ± 8.2). All participants underwent a clinical investigation and an anthropometric evaluation (weight, height, waist circumference (WC)). Abdominal obesity (АО) was confirmed at WC ≥ 94 cm in males and ≥ 88 cm in females. Fasting plasma glucose and lipid spectrum tests were performed. An ultrasound assessment of carotid intima-media thickness (IMT) was performed using a 7.5 MHz transducer (Phillips-SD 800). RESULTS: MS was revealed in 61 (42.4%; 47.8% in men and 37.3% in women) of the investigated patients. IMT was significantly increased with the presence of MS components in males (no components vs 2 components of MS: 0.67 ± 0.007 and 0.81 ± 0.009 respectively; р < 0.05) and females (no components vs 3 components of MS: 0.63 ± 0.007 and 0.76 ± 0.01 respectively; р < 0.01). IMT trended towards an increase in the presence of a greater number of MS components in patients with and without AO (р < 0.01). In order to identify independent factors affecting IMT we carried out a multifactorial logistic regression analysis. Arterial hypertension was found to have the greatest influence on the development of MS (OR = 3.81, p < 0.0001). CONCLUSION: In the group of ethnic Kyrgyzs, a greater number of MS components, with AO or without AO, is associated with higher carotid IMT.

Association between sleep apnoea and pulmonary hypertension in Kyrgyz highlanders.

This case-control study evaluates a possible association between high altitude pulmonary hypertension (HAPH) and sleep apnoea in people living at high altitude.Ninety highlanders living at altitudes >2500 m without excessive erythrocytosis and with normal spirometry were studied at 3250 m (Aksay, Kyrgyzstan); 34 healthy lowlanders living below 800 m were studied at 760 m (Bishkek, Kyrgyzstan). Echocardiography, polysomnography and other outcomes were assessed. Thirty-six highlanders with elevated mean pulmonary artery pressure (mPAP) >30 mmHg (31-42 mmHg by echocardiography) were designated as HAPH+. Their data were compared to that of 54 healthy highlanders (HH, mPAP 13-28 mmHg) and 34 healthy lowlanders (LL, mPAP 8-24 mmHg).The HAPH+ group (median age 52 years (interquartile range 47-59) had a higher apnoea-hypopnoea index (AHI) of 33.8 events·h-1 (26.9-54.6) and spent a greater percentage of the night-time with an oxygen saturation <90% (T<90; 78% (61-89)) than the HH group (median age 39 years (32-48), AHI 9.0 events·h-1 (3.6-16), T<90 33% (10-69)) and the LL group (median age 40 years (30-47), AHI 4.3 events·h-1 (1.4-12.6), T<90 0% (0-0)); p<0.007 for AHI and T<90, respectively, in HAPH+ versus others. In highlanders, multivariable regression analysis confirmed an independent association between mPAP and both AHI and T<90, when controlled for age, gender and body mass index.Pulmonary hypertension in highlanders is associated with sleep apnoea and hypoxaemia even when adjusted for age, gender and body mass index, suggesting pathophysiologic interactions between pulmonary haemodynamics and sleep apnoea.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Rationale and Design.

Familial hypercholesterolemia (FH) is a genetic disorder with well-known genetic transmission and clinical course. Despite great recent progress, FH is still underestimated, under-diagnosed and thus undertreated. Furthermore it represents a significant healthcare challenge as a common risk factor for the premature development of coronary heart disease. The ScreenPro FH Project is an international network project aiming at improving complex care - from timely screening, through diagnosis to up-to-date treatment of familial hypercholesterolemia in Central, Eastern and Southern Europe. An important task for the project is to harmonise and unify diagnostic and therapeutic approaches in participating countries, where the situation differs from country to country. Countries with more experience should serve as a model for countries developing the FH network.Key words: diagnosis - familial hypercholesterolemia - screening - treatment optimization.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Basic Epidemiology.

INTRODUCTION: Despite great recent progress, familial hypercholesterolemia (FH) is still underestimated, under-diagnosed and thus undertreated worldwide. We have very little information on exact prevalence of patients with FH in the Central, Eastern and Southern Europe (CESE) region. The aim of the study was to describe the epidemiological situation in the CESE region from data available. METHODS: All local leaders of the ScreenPro FH project were asked to provide local data on (a) expert guess of FH prevalence (b) the medical facilities focused on FH already in place (c) the diagnostic criteria used (d) the number of patients already evidenced in local database and (e) the availability of therapeutic options (especially plasma apheresis). RESULTS: With the guess prevalence of FH around 1 : 500, we estimate the overall population of 588 363 FH heterozygotes in the CESE region. Only 14 108 persons (2.4 %) were depicted in local databases; but the depiction rate varied between 0.1 % and 31.6 %. Only four out of 17 participating countries reported the the LDL apheresis availability. CONCLUSION: Our data point to the large population of heterozygous FH patients in the CESE region but low diagnostic rate. However structures through the ScreenPro FH project are being created and we can hope that the results will appear soon.Key words: diagnosis - epidemiology - familial hypercholesterolemia - screening.

Prevalence of health risk behaviors and their associated factors among university students in Kyrgyzstan.

BACKGROUND: With the advancements in knowledge about health promotion, public health professionals have been seeking determinants of personal health behaviors. The purpose of this study was to assess the prevalence of health risk behaviors and its associated factors in a sample of Kyrgyz university students. METHODS: In a cross-sectional survey, health risk behaviors among a sample of randomly selected university students were assessed. The sample included 837 university students from health sciences undergraduate courses of the State Medical Academy in Kyrgyzstan. The students were 358 (42.8%) males and 479 (57.2%) females in the age range of 18-29 years (Median age=21.3 years, SD=1.5). RESULTS: On average, students engaged in 9.4 (SD=2.3) out of 23 health risk behavior practices (range, 3-18). Generally, there was a high rate of insufficient fruit and vegetable intake (86.4%), eating red meat at least once a day (62%), usually adding salt to meals (78.3%), skipping breakfast (50.5%), current tobacco use (49.7%) and two or more sexual partners in the past 12 months (46.1%) among men, and never using a condom with a primary partner in the past 3 months (90.9%) among women. Furthermore, 60.8% of the women were physically inactive. In bivariate analysis among men, the lack of perceived benefits was associated with health risk behavior. In multivariate analysis among women, poorer family background, being Russian, high personal constraints or stress, and better subjective health were associated with the health risk behavior index. CONCLUSIONS: Students had a high proportion of health risk behavior practices. Several high health risk practices were identified, including poor dietary behavior, physical inactivity, sexual risk behavior, and tobacco use. Gender specific predictors identified included sociodemographic characteristics and social and health variables, which can be utilized in health promotion programs.

Lipids and leptin level in natives of Kyrgyzstan.

OBJECTIVES: A possible link between obesity and impaired lipid metabolism is leptin, the 167-amino acid protein, secreted by adipocytes. The content of leptin in the body is closely associated with body mass index (BMI). Data obtained from studies on the association of leptin with dyslipidemia are contradictory. The level of leptin has not been studied in the ethnic Kyrgyz population previously. The purpose of this study was to investigate the relationship between leptin and lipid parameters in a group of ethnic Kyrgyz. STUDY DESIGN: The study included 322 ethnic Kyrgyz (145 males, 177 females) aged ≥30 years, living in Kyrgyzstan. Measurement of anthropometric parameters (height, weight, waist circumference [WC], hip circumference [HC]) and blood pressure (BP) was done. Laboratory tests included blood glucose (fasting) in plasma, lipid profile (total cholesterol [TC], triglycerides [TG], high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol), and serum leptin. RESULTS: Leptin was positively correlated with BMI, WC and TG in both sexes and with TC in males. CONCLUSION: Leptin is associated with BMI, WC and TG in both sexes of Kyrgyz and with TC in Kyrgyz males.

Association of leptin receptor gene Gln223Arg polymorphism with insulin resistance and hyperglycemia in patients with metabolic syndrome.

Introduction: Worldwide, there has been an increase in the incidence of metabolic syndrome. The search for genetic markers of this syndrome is ongoing. The leptin receptor has recently received attention. One of the polymorphisms (Gln223Arg) is possibly associated with the development of obesity and insulin resistance. However, the results of studies on this polymorphism remain equivocal. Gln223Arg polymorphism has not been studied previously in the Kyrgyz population. Thus, we aimed to investigate the possible association of the Gln223Arg polymorphism of the leptin receptor gene with metabolic syndrome components in the Kyrgyz population. Material and methods: 237 Kyrgyz subjects, aged 35-70 years, were studied. For the analysis anthropometric data, glucose, insulin, lipid spectrum, leptin were obtained. The genotype of the Gln223Arg leptin polymorphism was evaluated using TaqMan real-time PCR. Results: The distribution of genotypes was as follows: Gln223Gln 46.4%, Gln223Arg 40.1%, Arg223Arg 13.5%. In the study no association was found with abdominal obesity, arterial hypertension, hypertriglyceridemia or low-density cholesterol levels. Relationships of Gln223Arg and Arg223Arg genotypes with insulin resistance (p < 0.03) were found. Gln223Arg polymorphism was associated with a higher level of glycemia (5.54 vs. 5.39 mmol/l, p < 0.05) and insulinemia (8.3 vs. 7.1 µIU/ml, p < 0.05). Correlation analysis showed that carriers of the Arg223 allele demonstrated a higher risk of insulin resistance (odds ratio (OR) = 1.83, 95% CI: 1.03-3.24; p < 0.03) than carriers of the Gln223 allele. Conclusions: Gln223Arg polymorphism of the leptin receptor gene may be a marker of predisposition to insulin resistance in the Kyrgyz population. Further studies are necessary to confirm these results in populations from other regions.

Prevalence and target attainment of traditional cardiovascular risk factors in patients with systemic lupus erythematosus: a cross-sectional study including 3401 individuals from 24 countries.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. METHODS: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. FINDINGS: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. INTERPRETATION: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. FUNDING: None.