Development of Portable Electronic Health Record Based Algorithms to Identify Individuals with Diabetic Retinopathy.

Objectives: To develop, validate and implement algorithms to identify diabetic retinopathy (DR) cases and controls from electronic health care records (EHR)s. Methods : We developed and validated EHR-based algorithms to identify DR cases and individuals with type I or II diabetes without DR (controls) in three independent EHR systems: Vanderbilt University Medical Center Synthetic Derivative (VUMC), the VA Northeast Ohio Healthcare System (VANEOHS), and Massachusetts General Brigham (MGB). Cases were required to meet one of three criteria: 1) two or more dates with any DR ICD-9/10 code documented in the EHR, or 2) at least one affirmative health-factor or EPIC code for DR along with an ICD9/10 code for DR on a different day, or 3) at least one ICD-9/10 code for any DR occurring within 24 hours of an ophthalmology exam. Criteria for controls included affirmative evidence for diabetes as well as an ophthalmology exam. Results: The algorithms, developed and evaluated in VUMC through manual chart review, resulted in a positive predictive value (PPV) of 0.93 for cases and negative predictive value (NPV) of 0.97 for controls. Implementation of algorithms yielded similar metrics in VANEOHS (PPV=0.94; NPV=0.86) and lower in MGB (PPV=0.84; NPV=0.76). In comparison, use of DR definition as implemented in Phenome-wide association study (PheWAS) in VUMC, yielded similar PPV (0.92) but substantially reduced NPV (0.48). Implementation of the algorithms to the Million Veteran Program identified over 62,000 DR cases with genetic data including 14,549 African Americans and 6,209 Hispanics with DR. Conclusions/Discussion: We demonstrate the robustness of the algorithms at three separate health-care centers, with a minimum PPV of 0.84 and substantially improved NPV than existing high-throughput methods. We strongly encourage independent validation and incorporation of features unique to each EHR to enhance algorithm performance for DR cases and controls.

Interaction between gut microbiota metabolites and dietary components in lipid metabolism and metabolic diseases.

Gut microbiota composition has caused perplexity in developing precision therapy to cure metabolic disorders. However, recent research has focused on using daily diet and natural bioactive compounds to correct gut microbiota dysbiosis and regulate host metabolism. Complex interactions between the gut microbiota and dietary compounds disrupt or integrate the gut barrier and lipid metabolism. In this review, we investigate the role of diet and bioactive natural compounds in gut microbiota dysbiosis and also the modulation of lipid metabolism by their metabolites. Recent studies have revealed that diet, natural compounds and phytochemicals impact significantly on lipid metabolism in animals and humans. These findings suggest that dietary components or natural bioactive compounds have a significant impact on microbial dysbiosis linked to metabolic diseases. The interaction between dietary components or natural bioactive compounds and gut microbiota metabolites can regulate lipid metabolism. Additionally, natural products can shape the gut microbiota and improve barrier integrity by interacting with gut metabolites and their precursors, even in unfavourable conditions, potentially contributing to the alignment of host physiology.

Fatty liver mediates the association of hyperuricemia with prediabetes and diabetes: a weighting-based mediation analysis.

Background: Fatty liver, obesity, and dyslipidemia are associated with prediabetes or diabetes risk, and hyperuricemia co-exists. The present study evaluated the role of multiple mediators, namely, fatty liver, body mass index (BMI), and dyslipidemia, in the association between hyperuricemia and diabetes status. Methods: Baseline data from the ongoing Fuqing cohort (5,336 participants) were analyzed to investigate the association of hyperuricemia with diabetes status using a multinomial logistic regression model. Furthermore, causal mediation analysis with the weighting-based approach was performed to estimate hyperuricemia's total natural direct effect (tnde), total natural indirect effect (tnie), and total effect (te) on prediabetes and diabetes risk, mediating jointly via fatty liver, BMI, and dyslipidemia. Results: In multinomial analysis without considering mediators' effects, hyperuricemia was associated with a higher risk of prediabetes only (odds ratio: 1.25; 95% CI: 1.09-1.43; p < 0.001). When fatty liver, BMI, and dyslipidemia were considered as multiple mediators in the association, hyperuricemia was linked to both prediabetes [tnde: 1.11, 95% CI: 1.04-1.11; tnie: 1.07, 95% CI: 1.05-1.09; and overall proportion mediated (pm): 42%, 95% CI: 27%-73%] and diabetes risk (tnde: 0.96, 95% CI: 0.82-1.14; tnie: 1.25, 95% CI: 1.18-1.33; and pm: 100%, 95% CI: 57%-361%). Hyperuricemia showed significant tnde, te, and tnie, mediated by fatty liver jointly with dyslipidemia (pm = 17%) or BMI (pm = 35%), on prediabetes risk. Conclusion: Hyperuricemia could increase prediabetes or diabetes risk, partially mediated by fatty liver, BMI, and dyslipidemia. Fatty liver is the crucial mediator in the association between hyperuricemia and prediabetes.

Association between urinary polycyclic aromatic hydrocarbon metabolites and diabetes mellitus among the US population: a cross-sectional study.

BACKGROUND: The primary aim of this study is to examine the association between urinary polycyclic aromatic hydrocarbons (PAHs) and diabetes mellitus (DM) among the US population. METHODS: We used data from the National Health and Nutritional Examination Survey 2003-16, which is a nationally representative population-based survey of the US non-institutionalized population. Logistic regression analysis was performed to evaluate the association between urinary PAHs and the prevalence of DM using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The study sample including 13 792 individuals ≥18 y of age. The average ages of the three PAH tertiles were 42.56±19.67, 42.21±19.51 and 43.39±17.99 y. An increased risk of DM was found with increased odds for the second (OR 1.56 [95% CI 1.36 to 1.79]) and third tertile (OR 1.79 [95% CI 1.55 to 2.06)] of urinary PAH as compared with the first tertile. Similarly, higher chances of DM were observed in the second (men: OR 1.42 [95% CI 1.18 to 1.71]; women: OR 1.76 [95% CI 1.44 to 2.14]) and third tertile (men: OR 1.69 [95% CI 1.38 to 2.08]; women: OR 1.79 [95% CI 1.46 to 2.19]) of urinary PAHs as compared with the first tertile in both men and women. CONCLUSIONS: A population-based cross-sectional study found a positive association between urinary PAHs and DM in the US population.

Cancer situation in China: what does the China cancer map indicate from the first national death survey to the latest cancer registration?

BACKGROUND: Over the past four decades, the Chinese government has conducted three surveys on the distribution of causes of death and built cancer registration. In order to shine a new light on better cancer prevention strategies in China, we evaluated the profile of cancer mortality over the forty years and analyzed the policies that have been implemented. METHODS: We described spatial and temporal changes in both cancer mortality and the ranking of major cancer types in China based on the data collected from three national surveys during 1973-1975, 1990-1992, 2004-2005, and the latest cancer registration data published by National Central Cancer Registry of China. The mortality data were compared after conversion to age-standardized mortality rates based on the world standard population (Segi's population). The geographical distribution characteristics were explored by marking hot spots of different cancers on the map of China. RESULTS: From 1973 to 2016, China witnessed an evident decrease in mortality rate of stomach, esophageal, and cervical cancer, while a gradual increase was recorded in lung, colorectal, and female breast cancer. A slight decrease of mortality rate has been observed in liver cancer since 2004. Lung and liver cancer, however, have become the top two leading causes of cancer death for the last twenty years. From the three national surveys, similar profiles of leading causes of cancer death were observed among both urban and rural areas. Lower mortality rates from esophageal and stomach cancer, however, have been demonstrated in urban than in rural areas. Rural areas had similar mortality rates of the five leading causes of cancer death with the small urban areas in 1973-1975. Additionally, rural areas in 2016 also had approximate mortality rates of the five leading causes with urban areas in 2004-2005. Moreover, stomach, esophageal, and liver cancer showed specific geographical distributions. Although mortality rates have decreased at most of the hotspots of these cancers, they were still higher than the national average levels during the same time periods. CONCLUSIONS: Building up a strong primary public health system especially among rural areas may be one critical step to reduce cancer burden in China.

Determinants of Voluntary Counseling and Testing Service Uptake Among Adult Sub-Saharan Africans: A Systematic Review and Meta-Analysis.

Objective: To examine the major determinants of VCT service uptake among adults in SSA. Methods: Electronic databases were searched to identify eligible English language publications. Reporting of the study selection procedure was done according to PRISMA and the selected articles were also critically appraised. Results: We found 8 significant determinants of VCT uptake among adults in SSA, such as less physical access [OR (Odds ratio): 0.77 (95% CI (Confidence interval): 0.62-0.96), p < 0.01], older age [OR: 1.36 (95% CI: 1.08-1.73), p < 0.01], higher education level [OR: 1.60 (95% CI: 1.24-2.05), p < 0.01], high knowledge of HIV and VCT awareness [OR: 1.40 (95% CI: 1.03-1.90), p < 0.01], unprotected sexual practices [OR: 1.75 (95% CI: 1.18-2.58), p < 0.01], discussion on HIV among partners and others [OR: 1.76 (95% CI: 1.10-2.81), p < 0.01], other STIs [OR: 1.40 (95% CI: 1.00-1.98), p < 0.01], and divorced/separated [OR: 1.39 (95% CI: 1.12-1.72), p < 0.01]. Conclusion: This study showed that 8 determinants were significantly associated with VCT service uptake in SSA. Thus, HIV interventions and policy initiatives should be tailored to these determinants to ensure scale-up of VCT service uptake in SSA.

Medical laboratory staff satisfaction and their perspective on the role of health institutions to combat COVID-19 pandemic.

OBJECTIVE: To assess the facilities and challenges encountered in the clinical laboratories, satisfaction of the medical laboratory staff (MLS) toward their profession and their views on the role of related health institutions during the first wave of the Coronavirus Disease 2019 (COVID-19) pandemic in Nepal. METHODS: A web-based cross-sectional study was conducted among registered MLS in Nepal. Data were collected using a structured self-reported questionnaire on the Google Docs platform. RESULTS: A total of 301 respondents were enrolled in the study; of which 180 were male and 121 were female. Of the 301 respondents, a lack of infrastructure was reported by 241 (80.1%), a lack of skill development training by 204 (67.8%), limited availability of diagnostics kits by 151 (50.2%), overburdened by the workload by 142 (47.2%) and difficulty in sample management by 129 (42.9%). A total of 244 of 301 respondents (81.1%) believed that stakeholder institutions should collaborate with the government during the pandemic. The level of satisfaction during the pandemic (130 of 301; 43.19%) was found to have decreased compared with before the pandemic (203 of 301; 67.4%). CONCLUSION: MLS were not fully satisfied with the available resources during the pandemic.

Overview on Thioredoxin-Interacting Protein (TXNIP): A Potential Target for Diabetes Intervention.

BACKGROUND: Diabetes mellitus (DM) is a common metabolic disorder characterized by a persistent increment of blood glucose. Type 2 DM is characterized by insulin resistance and ß-cell dysfunction. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of pancreatic ß-cells. OBJECTIVE: Recent studies have shown that high glucose can significantly up-regulate the expression of the TXNIP. Overexpression of TXNIP in ß-cells not only induced apoptosis but also decreased the production of insulin. At the same time, TXNIP deficiency protected the apoptosis of ß-cells, leading to increased insulin production. Therefore, finding small molecules that can modulate TXNIP expression and downstream signalling pathways is essential. Thus, the inhibition of TXNIP has beneficial effects on the cardiovascular system and other tissues such as the heart and the kidney in DM. Therefore, DM treatment must target small TXNIP activity, inhibit expression, and promote endogenous cell mass and insulin production. CONCLUSION: This review briefly describes the effect mechanism, regulatory mechanism, and crystal structure of TXNIP. In addition, we highlight how TXNIP signalling networks contribute to diabetes and interact with drugs that inhibit the development often and its complexes. Finally, the current status and prospects of TXNIP targeted therapy are also discussed.

Knowledge, practice and psychological symptoms among medical laboratory staff during COVID-19 pandemic in Nepal: An online based survey.

INTRODUCTION: Despite several attempts to control COVID-19, there was a continuous rise in the number of cases, and this has left questions unanswered on the availability of health resources in Nepal. Here, we tried to assess the level of knowledge, practice and psychological symptoms among medical laboratory staff. METHODS: An online survey was conducted in February 2021. A total of 301 completely filled responses were used to assess knowledge, practice and psychological distress. R-language software was used for data analysis and p-value less than 0.05 was considered statistically significant. RESULTS: Of the total 301 respondents, 180 (59.8%) were male and 121 (40.2%) were female. The average score of knowledge obtained in this study was 32.4 ± 5.7 on a 56-point scale. Knowledge level was significantly different among age-groups (p-value - 0.034). The average practice score obtained was 2.25 ± 0.91 on a 4-point scale. More than one psychological distress symptom was observed in nearly half (41.5%) of the participants. CONCLUSION: We conclude that medical laboratory staff in Nepal has satisfactory levels of knowledge and practice and, larger number of them has psychological distress. The study recommends further improvement in an effective information flow system, regular training, social security and psychological support.

Investigation of the relationships between sleep behaviors and risk of healthspan termination: a prospective cohort study based on 323,373 UK-Biobank participants.

OBJECTIVES: To examine the associations between four sleep behaviors and the risk of healthspan termination. METHODS: This study included 323,373 participants, free of terminated healthspan at baseline, from the UK-Biobank (UKB). We applied multivariable-adjusted Cox regression models to estimate the risk of terminated healthspan based on four sleep behaviors (insomnia/sleeplessness, napping, daytime sleepiness, and difficulty getting up from bed), which were self-reported and measured on Likert scales from "usually" to "never/rarely" experiences. In this study, healthspan was defined based on eight events that are strongly associated with longevity (congestive heart failure, myocardial infarction, chronic obstructive pulmonary disease, stroke, dementia, diabetes, cancer, and death). RESULTS: Participants who reported the following unhealthy sleep behaviors had a significantly higher risk of terminated healthspan: "usually experience sleeplessness/insomnia" (HR = 1.05, 95% CI: 1.03-1.07; P < 0.001); "usually nap" (HR = 1.22, 95% CI: 1.18-1.26; P < 0.01); "excessive daytime sleepiness" (HR = 1.25, 95% CI: 1.19-1.32; P < 0.001); and "difficult getting up from bed" (HR = 1.08, 95% CI: 1.05-1.10; P < 0.001). The corresponding population attributable risk percentage (PAR%) indicated that about 7% of healthspan termination in this cohort would have been eliminated if all participants had healthy sleep behaviors. CONCLUSION: Participants who reported "usually experience sleeplessness/insomnia," "usually nap," "excessive daytime sleepiness," and "difficult getting up from bed" had increased risk of shortened healthspan. Therefore, adherence to healthy sleep behavior is significant for the extension of healthspan.

A non-traditional dietary pattern increases risk of coronary artery disease in the Nepalese population.

OBJECTIVES: Several dietary patterns are associated with cardiovascular diseases. Traditional, Western, Mediterranean, and vegetarian are common dietary patterns, derived from principal component analysis (PCA) of dietary food intakes associated with cardiovascular diseases; however, these patterns were derived mostly from the diet habits of people in Western and European countries. Therefore, the present study aimed to determine dietary patterns linked with coronary artery disease (CAD) in the Nepalese population. METHODS: Food frequency questionnaires were used to estimate dietary intakes in 306 people with CAD and 306 people in a control group matched for age and sex. PCA was performed to deduce the dietary patterns, and conditional logistic regression was executed to determine the association of the dietary patterns with CAD. RESULTS: The component of PCA with higher loadings of refined grain, sugar, and meat and lower loadings of milk, whole grain, and fruit was named the non-traditional dietary pattern in the present study. We found a 34% increased risk of CAD (odds ratio, 1.34; 95% confidence interval, 1.14-1.58; P < 0.001) associated with this dietary pattern after adjusting for smoking, physical activity, and cardiometabolic risk factors. Dietary-pattern scores were further categorized into tertiles, and the third tertile was observed with significanly higher odds of CAD than the first tertile (odds ratio, 2.32; 95% confidence interval, 1.3-4.14; P for trend = 0.004). CONCLUSIONS: PCA-derived non-traditional dietary patterns can be a risk for developing CAD in Nepalese people. However, further cohort studies or randomized community trials are suggested to confirm our findings.

Combating the COVID-19 Pandemic: Experiences of the First Wave From Nepal.

Unprecedented and unforeseen highly infectious Coronavirus Disease 2019 (COVID-19) has become a significant public health concern for most of the countries worldwide, including Nepal, and it is spreading rapidly. Undoubtedly, every nation has taken maximum initiative measures to break the transmission chain of the virus. This review presents a retrospective analysis of the COVID-19 pandemic in Nepal, analyzing the actions taken by the Government of Nepal (GoN) to inform future decisions. Data used in this article were extracted from relevant reports and websites of the Ministry of Health and Population (MoHP) of Nepal and the WHO. As of January 22, 2021, the highest numbers of cases were reported in the megacity of the hilly region, Kathmandu district (population = 1,744,240), and Bagmati province. The cured and death rates of the disease among the tested population are ~98.00 and ~0.74%, respectively. Higher numbers of infected cases were observed in the age group 21-30, with an overall male to female death ratio of 2.33. With suggestions and recommendations from high-level coordination committees and experts, GoN has enacted several measures: promoting universal personal protection, physical distancing, localized lockdowns, travel restrictions, isolation, and selective quarantine. In addition, GoN formulated and distributed several guidelines/protocols for managing COVID-19 patients and vaccination programs. Despite robust preventive efforts by GoN, pandemic scenario in Nepal is, yet, to be controlled completely. This review could be helpful for the current and future effective outbreak preparedness, responses, and management of the pandemic situations and prepare necessary strategies, especially in countries with similar socio-cultural and economic status.

Associations Between Sleep Quality and Health Span: A Prospective Cohort Study Based on 328,850 UK Biobank Participants.

OBJECTIVE: To examine the associations between sleep quality and health span using a prospective cohort design based on the UK Biobank (UKB). MATERIALS AND METHODS: This longitudinal cohort study enrolled 328,850 participants aged between 37 and 73 years from UKB to examine the associations between sleep quality and risk of terminated health span. End of health span was defined by eight events strongly associated with longevity (cancer, death, congestive heart failure, myocardial infarction, chronic obstructive pulmonary disease, stroke, dementia, and diabetes), and a sleep score was generated according to five sleep behavioral factors (sleep duration, chronotype, sleeplessness, daytime sleepiness, and snoring) to characterize sleep quality. The hazard ratio (HR) and 95% confidence intervals (CIs) were calculated by multivariate-adjusted Cox proportional hazards model. Moreover, we calculated population attributable risk percentage (PAR%) to reflect the public health significance of healthy sleep quality. RESULTS: Compared with poor sleep quality, participants with healthy sleep quality had a 15% (HR: 0.85, 95% CI: 0.81-0.88) reduced risk of terminated health span, and those of less-healthy sleep quality had a 12% (HR: 0.88, 95% CI: 0.85-0.92) reduced risk. Linear trend results indicated that the risk of terminated health span decreased by 4% for every additional sleep score. Nearly 15% health span termination events in this cohort would have been prevented if a healthy sleep behavior pattern was adhered to (PAR%: 15.30, 95% CI: 12.58-17.93). CONCLUSION: Healthy sleep quality was associated with a reduced risk of premature end of health span, suggesting healthy sleep behavior may extend health span. However, further studies are suggested for confirmation of causality and potential mechanism.

A Multilevel Analysis to Determine the Factors Associated with Institutional Delivery in Nepal: Further Analysis of Nepal Demographic and Health Survey 2016.

BACKGROUND: One out of two neonatal deaths and 2 out of 5 maternal deaths occur at home in Nepal. An essential intervention in reducing maternal mortality and neonatal death is institutional delivery. The objective of this study was to find out the external environmental, predisposing, and enabling factors associated with the use of institutional delivery care in Nepal. METHODS: Data from Nepal Demographic and Health Surveys (NDHS) 2016 was used to estimate socio-economic, provincial, and use of media differentials with institutional delivery under the Andersen behavioral model framework using multilevel regression analysis. RESULTS: More than half of the women (60.9%) among 3899 women with last birth had their babies delivered in a health facility. In the multilevel logistic regression analysis, we found that women from province 2 (OR = 0.47 95%CI: 0.28-0.79) were significantly less likely to deliver in health institutions, and province 7 (OR = 1.76, 95%CI: 1.05-2.94) were significantly more likely deliver in a health institution. Age (OR = 0.94, 95%CI: 0.92-0.95) was also significantly associated with the place of delivery. Women with higher education (OR = 3.17, 95%CI: 2.09-4.81) were most likely to go for institutional delivery. The odds of women opting for institutional delivery were 3 folds more for those who had visited Antenatal Care (ANC) 4 or more times compared to those who did not. CONCLUSION: The results highlight the need for governments and health care providers to emphasize the promotion of institutional delivery and ANC visits as per protocol with a special focus on underprivileged communities. The use of multi-media is a vital strategy to promote the use of institutional delivery services.

Causal effects of dietary calcium, zinc and iron intakes on coronary artery disease in men: G-estimation and inverse probability of treatment weighting (IPTW) analyses.

BACKGROUND & AIMS: Dietary minerals have significant effects on the risk of cardiovascular disease. However, the results of previous studies were not uniform across different countries. The current study aims to determine the causal effects of dietary calcium, zinc, and iron intakes on coronary artery disease (CAD) among Nepalese men. METHODS: A matched case-control study was carried out at Shahid Gangalal National Heart Center. Dietary intakes of 466 male participants over the past 12 months were evaluated using a semi-quantitative customized food frequency questionnaire. G-estimation and inverse probability treatment weighting (IPTW) analyses were performed to determine the causal odds of CAD due to dietary calcium, zinc, and iron intakes. RESULTS: Daily dietary calcium, zinc, and iron intakes were categorized into two groups: less than versus more than the median value and less than versus equal or more than recommended daily allowance (RDA). In G-estimation, dietary calcium intake was inversely associated with CAD in both medians (OR: 91; 91%CI: 0.86, 95) and RDA categories (OR: 0.88: 95%CI: 0.84, 0.97). However, in IPTW analysis, only median calcium intake was significantly associated with CAD (OR: 7; 91%CI: 0.5, 98). We observed a significant inverse association of equal or more than RDA of dietary zinc intake with CAD (OR: 0.91: 95%CI: 0.87, 0.96 in G-estimation, OR: 0.73: 95%CI: 0.66, 0.82 in IPTW); however, more than median dietary zinc intake showed inverse but not significant association with CAD in both analyses. Dietary iron intake was inversely but not significantly associated with CAD in G-estimation in both groups. Nevertheless, in IPTW analysis, equal or more than RDA iron intake was significantly positively (OR: 1.4; 95%CI: 1.14, 1.73) related to CAD. CONCLUSIONS: A significant inverse association of dietary zinc intake above RDA indicates the potential protective effect of higher dietary zinc against CAD. However, causal odds of CAD are inconsistent across the median or RDA of calcium and iron intakes. Therefore, cohort and randomized clinical trial studies with a large sample size are recommended to substantiate these nutrients' causal link with CAD development in the Nepalese population.

Xanthine Oxidase and Transforming Growth Factor Beta-activated Kinase 1: Potential Targets for Gout Intervention.

BACKGROUND: Gout, inflammatory arthritis caused by the deposition of monosodium urate crystals into affected joints and other tissues, has become one of the major health problems of today's world. The main risk factor for gout is hyperuricemia, which may be caused by excessive or insufficient excretion of uric acid. The incidence is usually in the age group of 30- 50 years, commonly in males. In developed countries, the incidence of gout ranges from 1 to 4%. Despite effective treatments, there has been an increase in the number of cases over the past few decades. OBJECTIVE: In recent years, the development of targeted drugs in gout has made significant achievements. The global impact of gout continues to increase, and as a result, the focus of disease-modifying therapies remains elusive. In addition, the characterization of available instrumental compounds is urgently needed to explore the use of novel selective and key protein-ligand interactions for the effective treatment of gout. Xanthine oxidase (XO) is a key target in gout to consider the use of XO inhibitors in patients with mild to moderate condition, however, the costs are high, and no other direct progress has been made. Despite many XO inhibitors, a selective potent inhibitor for XO is limited. Likewise, in recent years, attention has been focused on different strategies for the discovery and development of new selectivity ligands against transforming growth factor beta- activated kinase 1 (TAK1), a potential therapeutic target for gout. Therefore, the insight on human XO structure and TAK1 provides a clue into protein-ligand interactions and provides the basis for molecular modeling and structure-based drug design. CONCLUSION: In this review, we briefly introduce the clinical characteristics, the development of crystal, inhibitors, and crystal structure of XO and TAK1 protein.

HDL cholesterol: A potential mediator of the association between urinary cadmium concentration and cardiovascular disease risk.

Evidence from previous studies has shown that exposure to metals is associated with cardiovascular disease (CVD). However, the association between metal mixtures and CVD risk and the potential mechanisms in epidemiologic studies remain unclear. The data of 14,795 adults who participated in the U.S. National Health and Nutrition Examination Survey (NHANES) 1999-2016 were analyzed. Multivariate logistic regression was performed to investigate the associations between urinary metal levels and CVDs. Weighted quantile sum (WQS) regression was performed to examine the effects of mixed metals on CVDs. Multivariate linear regression and mediation analysis were conducted to explore the associations between metals and blood lipids. Urinary cadmium (Cd) was significantly associated with an increased total CVD risk and with individual CVD risk. The odds ratio (OR) for CVD in the highest quartile of the WQS index was 1.43 (95% confidence interval [CI]: 1.19, 1.71). One augmented urinary Cd concentration unit (Log10) was associated with a 0.93 mg/dL decrease in HDL cholesterol, a 1.34 mg/dL increase in LDL cholesterol and a 1.30 mg/dL increase in total cholesterol in the fully adjusted model. Mediation analysis showed that HDL cholesterol mediated 4.91% of the association between urinary Cd and the prevalence of CVD. Our findings suggest that urinary Cd and metal mixtures were significantly and positively associated with CVD. The downregulation of HDL cholesterol might play a significant role in mediating Cd exposure-associated CVD risk increases.

Dietary nutrients of relative importance associated with coronary artery disease: Public health implication from random forest analysis.

Dietary nutrients have significant effects on the risk of cardiovascular diseases. However, the results were not uniform across different countries. The study aims to determine the relative importance of dietary nutrients associated with coronary artery disease (CAD) among the Nepalese population. A hospital-based matched case-control study was carried out at Shahid Gangalal National Heart Center in Nepal. In the present study, patients with more than seventy percent stenosis in any main coronary artery branch in angiography were defined as cases, while those presenting normal coronary angiography or negative for stressed exercise test were considered controls. Dietary intakes of 612 respondents over the past 12 months were evaluated using a semi-quantitative customized food frequency questionnaire. In conditional regression model, the daily average dietary intake of ß-carotene (OR: 0.54; 95%CI: 0.34, 0.87), and vitamin C (OR: 0.96; 95%CI: 0.93, 0.99) were inversely, whereas dietary carbohydrate (OR: 1.16; 95%CI: 1.1, 1.24), total fat/oil (OR: 1.47; 95%CI: 1.27, 1.69), saturated fatty acid (SFA) (OR: 1.2; 95%CI: 1.11, 1.3), cholesterol (OR: 1.01; 95%CI: 1.001, 1.014), and iron intakes (OR: 1.11; 95%CI: 1.03, 1.19) were positively linked with CAD. Moreover, in random forest analysis, the daily average dietary intakes of SFA, vitamin A, total fat/oil, ß-carotene, and cholesterol were among the top five nutrients (out of 12 nutrients variables) of relative importance associated with CAD. The nutrients of relative importance imply a reasonable preventive measure in public health nutrients specific intervention to prevent CAD in a resource-poor country like Nepal. The findings are at best suggestive of a possible relationship between these nutrients and the development of CAD, but prospective cohort studies and randomized control trials will need to be performed in the Nepalese population.