Association between public health policies on alcohol and worldwide cancer, liver disease and cardiovascular disease outcomes.

BACKGROUND & AIMS: The long-term impact of alcohol-related public health policies (PHPs) on disease burden is unclear. We aimed to assess the association between alcohol-related PHPs and alcohol-related health consequences. METHODS: We conducted an ecological multi-national study including 169 countries. We collected data on alcohol-related PHPs from the WHO Global Information System of Alcohol and Health 2010. Data on alcohol-related health consequences between 2010-2019 were obtained from the Global Burden of Disease database. We classified PHPs into five items, including criteria for low, moderate, and strong PHP establishment. We estimated an alcohol preparedness index (API) using multiple correspondence analysis (0 lowest and 100 highest establishment). We estimated an incidence rate ratio (IRR) for outcomes according to API using adjusted multilevel generalized linear models with a Poisson family distribution. RESULTS: The median API in the 169 countries was 54 [IQR 34.9-76.8]. The API was inversely associated with alcohol use disorder (AUD) prevalence (IRR 0.13; 95% CI 0.03-0.60; p = 0.010), alcohol-associated liver disease (ALD) mortality (IRR 0.14; 95% CI 0.03-0.79; p = 0.025), mortality due to neoplasms (IRR 0.09; 95% CI 0.02-0.40; p = 0.002), alcohol-attributable hepatocellular carcinoma (HCC) (IRR 0.13; 95% CI 0.02-0.65; p = 0.014), and cardiovascular diseases (IRR 0.09; 95% CI 0.02-0.41; p = 0.002). The highest associations were observed in the Americas, Africa, and Europe. These associations became stronger over time, and AUD prevalence was significantly lower after 2 years, while ALD mortality and alcohol-attributable HCC incidence decreased after 4 and 8 years from baseline API assessment, respectively (p <0.05). CONCLUSIONS: The API is a valuable instrument to quantify the robustness of alcohol-related PHP establishment. Lower AUD prevalence and lower mortality related to ALD, neoplasms, alcohol-attributable HCC, and cardiovascular diseases were observed in countries with a higher API. Our results encourage the development and strengthening of alcohol-related policies worldwide. IMPACT AND IMPLICATIONS: We first developed an alcohol preparedness index, an instrument to assess the existence of alcohol-related public policies for each country. We then evaluated the long-term association of the country's alcohol preparedness index in 2010 with the burden of chronic liver disease, hepatocellular carcinoma, other neoplasms, and cardiovascular disease. The strengthening of alcohol-related public health policies could impact long-term mortality rates from cardiovascular disease, neoplasms, and liver disease. These conditions are the main contributors to the global burden of disease related to alcohol use. Over time, this association has not only persisted but also grown stronger. Our results expand the preliminary evidence regarding the importance of public health policies in controlling alcohol-related health consequences.

Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease.

BACKGROUND: The prognoses with respect to mortality and hepatic and nonhepatic outcomes across the histologic spectrum of nonalcoholic fatty liver disease (NAFLD) are not well defined. METHODS: We prospectively followed a multicenter patient population that included the full histologic spectrum of NAFLD. The incidences of death and other outcomes were compared across baseline histologic characteristics. RESULTS: A total of 1773 adults with NAFLD were followed for a median of 4 years. All-cause mortality increased with increasing fibrosis stages (0.32 deaths per 100 person-years for stage F0 to F2 [no, mild, or moderate fibrosis], 0.89 deaths per 100 persons-years for stage F3 [bridging fibrosis], and 1.76 deaths per 100 person-years for stage F4 [cirrhosis]). The incidence of liver-related complications per 100 person-years increased with fibrosis stage (F0 to F2 vs. F3 vs. F4) as follows: variceal hemorrhage (0.00 vs. 0.06 vs. 0.70), ascites (0.04 vs. 0.52 vs. 1.20), encephalopathy (0.02 vs. 0.75 vs. 2.39), and hepatocellular cancer (0.04 vs. 0.34 vs. 0.14). As compared with patients with stage F0 to F2 fibrosis, patients with stage F4 fibrosis also had a higher incidence of type 2 diabetes (7.53 vs. 4.45 events per 100 person-years) and a decrease of more than 40% in the estimated glomerular filtration rate (2.98 vs. 0.97 events per 100 person-years). The incidence of cardiac events and nonhepatic cancers were similar across fibrosis stages. After adjustment for age, sex, race, diabetes status, and baseline histologic severity, the incidence of any hepatic decompensation event (variceal hemorrhage, ascites, or encephalopathy) was associated with increased all-cause mortality (adjusted hazard ratio, 6.8; 95% confidence interval, 2.2 to 21.3). CONCLUSIONS: In this prospective study involving patients with NAFLD, fibrosis stages F3 and F4 were associated with increased risks of liver-related complications and death. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; NAFLD DB2 ClinicalTrials.gov number, NCT01030484.).

Gender differences in the association of individual and contextual socioeconomic status with hypertension in 230 Latin American cities from the SALURBAL study: a multilevel analysis.

BACKGROUND: Despite global interest in gender disparities and social determinants of hypertension, research in urban areas and regions with a high prevalence of hypertension, such as Latin America, is very limited. The objective of this study was to examine associations of individual- and area-level socioeconomic status with hypertension in adults living in 230 cities in eight Latin America countries. METHODS: In this cross-sectional study, we used harmonized data from 109,184 adults (aged 18-97 years) from the SALURBAL (Salud Urbana en America Latina/Urban Health in Latin America) project. Hypertension was assessed by self-report. Individual-, sub-city- and city-level education were used as proxies of socioeconomic status. All models were stratified by gender. RESULTS: Higher individual-level education was associated with lower odds of hypertension among women (university education or higher versus lower than primary: odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.61-0.74) but higher odds among men (OR = 1.65; 95%CI 1.47-1.86), although in men an inverse association emerged when measured blood pressure was used (OR = 0.86; 95%CI 0.76-0.97). For both genders, living in sub-city areas with higher educational achievement was associated with higher odds of hypertension (OR per standard deviation [SD] = 1.07, 95%CI = 1.02-1.12; OR = 1.11 per SD, 95%CI = 1.05-1.18, for women and men, respectively). The association of city-level education with hypertension varied across countries. In Peru, there was an inverse association (higher city level education was associated with lower odds of hypertension) in women and men, but in other countries no association was observed. In addition, the inverse association of individual-level education with hypertension became stronger (in women) or emerged (in men) as city or sub-city education increased. CONCLUSION: The social patterning of hypertension differs by gender and by the level of analysis highlighting the importance of context- and gender-sensitive approaches and policies to reduce the prevalence of hypertension in Latin America.

Impact of Public Health Policies on Alcohol-Associated Liver Disease in Latin America: An Ecological Multinational Study.

BACKGROUND AND AIMS: Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality in Latin America, yet the impact of public health policies (PHP) on liver disease is unknown. We aimed to assess the association between alcohol PHP and deaths due to ALD in Latin American countries. APPROACH AND RESULTS: We performed an ecological multinational study including 20 countries in Latin America (628,466,088 inhabitants). We obtained country-level sociodemographic information from the World Bank Open Data source. Alcohol-related PHP data for countries were obtained from the World Health Organization Global Information System of Alcohol and Health. We constructed generalized linear models to assess the association between the number of PHP (in 2010) and health outcomes (in 2016). In Latin America, the prevalence of obesity was 27% and 26.1% among male and female populations, respectively. The estimated alcohol per capita consumption among the population at 15 years old or older was 6.8 L of pure alcohol (5.6 recorded and 1.2 unrecorded). The overall prevalence of alcohol use disorders (AUD) was 4.9%. ALD was the main cause of cirrhosis in 64.7% of male and 40.0% of female populations. A total of 19 (95%) countries have at least one alcohol-related PHP on alcohol. The most frequent PHP were limiting drinking age (95%), tax regulations (90%), drunk-driving policies and countermeasures (90%), and government monitoring systems and community support (90%). A higher number of PHP was associated with a lower ALD mortality (PR, 0.76; 95% CI, 0.61-0.93; P = 0.009), lower AUD prevalence (PR, 0.80; 95% CI, 0.65-0.99; P = 0.045), and lower alcohol-attributable road traffic deaths (PR, 0.81; 95% CI, 0.65-1.00; P = 0.051). CONCLUSIONS: Our study indicates that in Latin America, countries with higher number of PHP have lower mortality due to ALD, lower prevalence of AUD, and lower alcohol-attributable road traffic mortality.

COVID-19 Outcomes Among the Hispanic Population of 27 Large US Cities, 2020-2021.

Objectives. To examine racial/ethnic disparities in COVID-19 outcomes between Hispanics and Whites across 27 US jurisdictions whose health departments are members of the Big Cities Health Coalition (BCHC). Methods. Using surveillance data from the BCHC COVID-19 dashboard as of mid-June 2021, we computed crude incidence, age-adjusted hospitalization and mortality, and full vaccination coverage rates for Hispanics and Whites by city. We estimated relative and absolute disparities cumulatively and for 2020 and 2021 and explored associations between city-level social vulnerability and the magnitude of disparities. Results. In most of the cities with available COVID-19 incidence data, rates among Hispanics were 2.2 to 6.7 times higher than those among Whites. In all cities, Hispanics had higher age-adjusted hospitalization (1.5-8.6 times as high) and mortality (1.4-6.2 times as high) rates. Hispanics had lower vaccination coverage in all but 1 city. Disparities in incidence and hospitalizations narrowed in 2021, whereas disparities in mortality remained similar. Disparities in incidence, hospitalization, mortality, and vaccination rates were wider in cities with lower social vulnerability. Conclusions. A deeper exploration of racial/ethnic disparities in COVID-19 outcomes is essential to understand and prevent disparities among marginalized communities. (Am J Public Health. 2022;112(7): 1034-1044. https://doi.org/10.2105/AJPH.2022.306809).

Are Women's Empowerment and Income Inequality Associated with Excess Weight in Latin American Cities?

While income gradients and gender inequalities in excess weight have been noted elsewhere, data from Latin American cities is lacking. We analyzed gender-specific associations between city-level women's empowerment and income inequality with individual-level overweight/obesity, assessing how these associations vary by individual education or living conditions within cities in Latin America. Data came from national surveys and censuses, and was compiled by the SALURBAL project (Urban Health in Latin America). The sample included 79,422 individuals (58.0% women), living in 538 sub-cities, 187 cities, and 8 countries. We used gender-stratified Poisson multilevel models to estimate the Prevalence Rate Ratios (PRR) for overweight/obesity (body mass index ≥ 25 kg/m2) per a unit change in city-level women's empowerment (proxied by a score that measures gender inequalities in employment and education) and income inequality (proxied by income-based Gini coefficient). We also tested whether individual education or sub-city living conditions modified such associations. Higher city labor women's empowerment (in women) and higher city Gini coefficient (in men) were associated with a lower prevalence of overweight/obesity (PRR = 0.97 (95%CI 0.94, 0.99) and PRR = 0.94 (95%CI 0.90, 0.97), respectively). The associations varied by individual education and sub-city living conditions. For labor women's empowerment, we observed weakened associations towards the null effect in women with lower education and in residents of sub-cities with worse living conditions (men and women). For the Gini coefficient, the association was stronger among men with primary education, and a negative association was observed in women with primary education. Our findings highlight the need for promoting equity-based policies and interventions to tackle the high prevalence of excess weight in Latin American cities.

Association of blood manganese, selenium with steatosis, fibrosis in the National Health and Nutrition Examination Survey, 2017-18.

BACKGROUND & AIMS: Chronic liver disease is a growing health burden worldwide. Chronic metal exposures may be associated with non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate the association of blood cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and selenium (Se) with two hallmark features of NAFLD: liver steatosis and fibrosis in the general U.S. METHODS: We analyzed transient liver elastography data from participants of the National Health and Nutrition Examination Survey (NHANES) 2017-18, using ordinal logistic regression analyses to evaluate the cross-sectional association between blood metal concentrations and clinical stages of steatosis and fibrosis. We applied survey weights, strata, and primary sampling units and analyses were conducted using the R survey package. RESULTS: 4,154 participants were included. Median (IQR) for blood Mn and blood Se were 9.28 (7.48-11.39) and 191.08 (176.55-207.16) µg/L, respectively. Per interquartile range increase of natural log transformed blood Mn, the adjusted odds ratio (OR) (95% CI) was 1.59 (1.13-2.23) for a higher grade of steatosis and 1.16 (0.67-2.00) for liver fibrosis. The corresponding OR for steatosis was 2.00 (1.24-3.24) and 2.14 (1.04-4.42) in Black and Mexican American participants, respectively. The corresponding OR for liver fibrosis was 2.96 (1.42-6.17) for females. Per interquartile range increase of natural log transformed blood Se, the adjusted OR was 2.25 (1.30-3.89) for steatosis but 0.31 (0.13-0.72) for liver fibrosis. The inverse association of blood Se with liver fibrosis was also observed in males and White participants. Blood Cd, Hg, and Pb were not associated with liver steatosis and fibrosis in fully-adjusted models overall. CONCLUSIONS: In NHANES 2017-18, higher blood Mn was positively associated with liver steatosis, and higher Se was positively associated with liver steatosis but negatively associated with liver fibrosis. Longitudinal studies are needed to examine the association of Mn and Se with fibrosis progression.

Accessibility and availability of alcohol outlets around schools: An ecological study in the city of Madrid, Spain, according to socioeconomic area-level.

Neighborhood accessibility and availability of alcohol products has been associated with increased alcohol consumption and harms among adolescents. This availability has been shown to be higher in neighborhoods with lower socio-economic status (SES). The aim of this study was to examine inequalities in alcohol outlet density and proximity around schools by area-level SES in Madrid, Spain. Data on schools, SES, alcohol outlets and population density at census tract level were obtained through public databases from the local government of Madrid. We examined (1) density as the number of alcohol outlets around schools within 3 buffers (i.e. 200 m, 400 m and 800 m) and (2) proximity as the distance from schools to their nearest alcohol outlet. We performed multilevel analyses to examine the associations between alcohol outlet density and proximity and SES, adjusted by population density. Secondary schools (n = 576) located in less deprived areas had lower densities of alcohol outlets at walking distances of 200 and 400 m (50% and 37% lower, respectively p < 0.05). No significant differences were found for the proximity measures. The socioeconomic level of the area in which adolescents go to school is a determinant of their exposure to alcohol, where those who study in high SES areas have lower exposure to alcohol outlets. This study highlights the need to prioritize equity in the design and implementation of policies to limit alcohol accessibility among adolescents, including establishing minimum distances between schools and alcohol outlets or limiting the number of outlets per inhabitant in neighborhoods.

Aging and self-reported health in 114 Latin American cities: gender and socio-economic inequalities.

BACKGROUND: Understanding how urban environments influence people's health, especially as individuals age, can help identify ways to improve health in the rapidly urbanizing and rapidly aging populations. OBJECTIVES: To investigate the association between age and self-reported health (SRH) in adults living in Latin-American cities and whether gender and city-level socioeconomic characteristics modify this association. METHODS: Cross-sectional analyses of 71,541 adults aged 25-97 years, from 114 cities in 6 countries (Argentina, Brazil, Colombia, Chile, El Salvador, and Guatemala), as part of the Salud Urbana en America Latina (SALURBAL) Project. We used individual-level age, gender, education, and self-reported health (SRH) data from harmonized health surveys. As proxies for socioeconomic environment we used a city-level socioeconomic index (SEI) calculated from census data, and gross domestic product (GDP) per-capita. Multilevel Poisson models with a robust variance were used to estimate relative risks (RR), with individuals nested in cities and binary SRH (poor SHR vs. good SRH) as the outcome. We examined effect modification by gender and city-level socioeconomic indicators. RESULTS: Overall, 31.4% of the sample reported poor SRH. After adjusting for individual-level education, men had a lower risk of poor SRH (RR = 0.76; CI 0.73-0.78) compared to women, and gender modified the association between age and poor SRH (p-value of interaction < 0.001). In gender stratified models, the association between older age and poor SRH was more pronounced in men than in women, and in those aged 25-65 than among those 65+ (RR/10 years = 1.38 vs. 1.10 for men, and RR/10 years = 1.29 vs. 1.02 for women). Living in cities with higher SEI or higher GDP per-capita was associated with a lower risk of poor SRH. GDP per-capita modified the association between age (25-65) and SRH in men and women, with SEI the interaction was less clear. CONCLUSIONS: Across cities in Latin America, aging impact on health is significant among middle-aged adults, and among men. In both genders, cities with lower SEI or lower GDP per-capita were associated with poor SRH. More research is needed to better understand gender inequalities and how city socioeconomic environments, represented by different indicators, modify exposures and vulnerabilities associated with aging.

Interaction Between Alcohol Consumption and PNPLA3 Variant in the Prevalence of Hepatic Steatosis in the US Population.

BACKGROUND & AIMS: To our knowledge, the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis has not been explored in a representative sample. To examine the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis in the US adult population. METHODS: Cross-sectional study of 4,674 adult participants of the Third National Health and Nutrition Examination Survey, Phase 2 (1991-1994) with data on PNPLA3 genotype, self-reported alcohol consumption, ultrasound-defined hepatic steatosis and socio-demographic characteristics. RESULTS: In 1991-1994 in the U.S. population, the weighted allele frequency of the G (risk) allele of the rs738409 at PNPLA3 was 25.4%. We confirmed both a J shaped association between alcohol consumption and hepatic steatosis among those with the CC genotype of PNPLA3, and a higher prevalence of hepatic steatosis among those with PNPLA3 gene G variant. We found evidence of an interaction of PNPLA3 G allele presence on the association between moderate alcohol consumption and hepatic steatosis on both the multiplicative (relative prevalence ratio [RPR]=1.95, 95% confidence interval [CI] 1.04-3.65) and additive scales (relative excess risk due to interaction=0.49, 95% CI 0.13-0.85). Compared to never drinkers, moderate alcohol drinking was associated with a 48% decreased risk of hepatic steatosis only among those without PNPLA3 G allele (PR=0.52, 95% CI 0.26-1.05), with no association among those with at least one copy of the PNPLA3 G allele (PR=1.02, 95% CI 0.68-1.54). CONCLUSIONS: Our results suggest that a highly common and strong genetic susceptibility to liver disease is modifiable by the level of alcohol consumption. Keeping alcohol consumption low may offset genetic predisposition to liver disease.

Understanding Immigration as a Social Determinant of Health: Cardiovascular Disease in Hispanics/Latinos and South Asians in the United States.

PURPOSE OF REVIEW: The main purpose of this review is to summarize the epidemiology of cardiovascular disease and its risk factors among two of the largest and most diverse immigrant groups in the United States (Hispanics/Latinos and South Asians). RECENT FINDINGS: While the migration process generates unique challenges for individuals, there is a wide heterogeneity in the characteristics of immigrant populations, both between and within regions of origin. Hispanic/Latino immigrants to the United States have lower levels of cardiovascular risk factors, prevalence, and mortality, but this assessment is limited by issues related to the "salmon bias." South Asian immigrants to the United States generally have higher levels of risk factors and higher mortality. In both cases, levels of risk factors and mortality generally increase with time of living in the United States (US). While immigration acts as a social determinant of health, associations between immigration and cardiovascular disease and its risk factors are complex and vary across subpopulations.

The association of sex steroid hormone concentrations with non-alcoholic fatty liver disease and liver enzymes in US men.

BACKGROUND & AIMS: This study aimed to analyse the association of sex hormone levels with liver enzyme levels and non-alcoholic fatty liver disease (NAFLD) in a nationally representative sample of men. METHODS: A total of 919 men from the US National Health and Nutrition Examination Study (NHANES) III were included in this cross-sectional analysis of data from 1988 to 1991. We used existing data on serum total and free testosterone, total and free estradiol, androstanediol glucuronide (AAG) and sex steroid-binding globulin (SHBG), and estimated their associations with aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and NAFLD, as determined using ultrasound, after adjusting for possible confounders including age, race, smoking, alcohol, physical activity, waist circumference and steroid hormones. RESULTS: Lower total testosterone (TT) and higher free estradiol were associated with higher odds of NAFLD after adjusting for confounders including the other sex hormones. Lower TT was associated with higher odds of elevated AST, but not ALT. Free testosterone, total estradiol, SHBG and AAG were not associated with NAFLD or liver enzymes. CONCLUSIONS: This study supports an inverse association between TT concentration and NAFLD in men independent of other sex hormones (SHBG, AAG and estradiol) and known risk factors, such as obesity, age and lifestyle. Exploration of whether TT might be a non-invasive marker for NAFLD diagnosis is warranted.

Alcohol Consumption and Risk of Hospitalizations and Mortality in the Atherosclerosis Risk in Communities Study.

BACKGROUND: Public health recommendations on the benefits and harms of moderate alcohol intake require a thorough and unbiased understanding of all potential effects of various levels and patterns of alcohol consumption. We seek to evaluate the associations between patterns of current and past alcohol consumption with hospitalizations and mortality. METHODS: Data came from a prospective cohort of 12,327 adults (56% women, 78% white, mean age 60 years) participating in the Atherosclerosis Risk in Communities study visit 3 (1993 to 1995). Current and past alcohol consumption was based on self-report. Hospitalizations and mortality were ascertained through December 31, 2017. Negative binomial and Cox proportional hazards regressions were used. RESULTS: 24.8% of the study population reported never drinking, 48.3% reported currently drinking without a history of heavy drinking, 4.2% reported currently drinking with a history of heavy drinking, 19.2% reported being former drinkers without a history of heavy drinking, and 3.4% reported being former drinkers with a history of heavy drinking. Compared to those who reported drinking ≤1 to 7 drinks/wk, never drinkers (incident rate ratio [IRR]: 1.21 (95% confidence interval 1.13, 1.29) and former drinkers with (IRR: 1.43 [1.26, 1.63]) or without (IRR: 1.21 [1.13, 1.30]) a history of heavy drinking had a positive association with all-cause hospitalization (p < 0.001). Those who reported drinking ≤1 to 7 drinks/wk had the lowest all-cause mortality rate (19.2 per 1,000 person-years [18.4, 20.1]) and former drinkers with a history of heavy drinking had the highest (43.7 per 1,000 person-years [39.0, 49.1]). CONCLUSIONS: The positive associations with hospitalization and mortality were stronger among never and former drinkers compared to those who consume ≤1 to 7 drinks/wk. Former drinkers with a history of heavy drinking had a stronger positive association with adverse health outcomes than former drinkers without a history of heavy drinking, highlighting the impact of this pattern of alcohol consumption.

Associations between Helicobacter pylori with nonalcoholic fatty liver disease and other metabolic conditions in Guatemala.

BACKGROUND: Previous studies have suggested an association between Helicobacter pylori (H pylori) and nonalcoholic fatty liver disease (NAFLD). The aim of the current study was to examine the association in Guatemala, a region with elevated prevalences of both H pylori and NAFLD. Associations between H pylori and other metabolic conditions were also examined, as were associations between H hepaticus and H bilis and the metabolic conditions. MATERIALS & METHODS: The analysis included 424 participants from a cross-sectional study in Guatemala. H pylori seropositivity was defined as positivity for ≥ 4 antigens. Seropositivities for H bilis and H hepaticus were defined as positivity for ≥ 2 antigens. NAFLD was estimated using the Fatty Liver Index and the Hepatic Steatosis Index. Other conditions examined were obesity, central obesity, hypercholesterolemia, low HDL, diabetes and metabolic syndrome (MetSyn). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated. RESULTS: No overall associations between H pylori,H hepaticus, or H bilis and NAFLD or related metabolic conditions were found. Seropositivity for H pylori antigens CagA and VacA and H hepaticus antigen HH0713 was each significantly associated with NAFLD, however. In addition, associations were observed between the H pylori antigens HyuA, HP1564, and UreA and specified metabolic conditions. CONCLUSIONS: While no overall associations between H pylori or Helicobacter species with NAFLD or related conditions were observed, some selected Helicobacter spp. antigens were associated with NAFLD. Further research is warranted to examine whether H. species are associated with any metabolic condition.

Recruitment of trial participants through electronic medical record patient portal messaging: A pilot study.

BACKGROUND/AIM: Cost-efficient methods are essential for successful participant recruitment in clinical trials. Patient portal messages are an emerging means of recruiting potentially eligible patients into trials. We assessed the response rate and complaint rate from direct-to-patient, targeted recruitment through patient portals of an electronic medical record for a clinical trial, and compared response rates by differences in message content. METHODS: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) trial is a National Institutes of Health-sponsored, community-based study of vitamin D supplementation for fall prevention in older adults conducted at Johns Hopkins. Potential participants were identified using the Epic electronic medical record at the Johns Hopkins Health System based on age (≥70 years), ZIP code (30-mile radius of study site), and prior activation of a patient portal account. We prepared a shorter message and a longer message. Both had basic information about study participation, but the longer message also contained information about the significance of the study and a personal invitation from the STURDY principal investigator. The Hopkins Institutional Review Board did not require prior consent from the patient or their providers. We calculated the response rate and tracked the number of complaints and requests for removal from future messages. We also determined response rate according to message content. RESULTS: Of the 5.5 million individuals receiving care at the Johns Hopkins Health System, a sample of 6896 met our inclusion criteria and were sent one patient portal recruitment message between 6 April 2017 and 3 August 2017. Assessment of enrollment by this method ended on 1 December 2017. There were 116 patients who expressed interest in the study (response rate: 1.7%). Twelve (0.2%) recipients were randomized. There were two complaints (0.03%) and one request to unsubscribe from future recruitment messages (0.01%). Response rate was higher with the longer message than the shorter message (2.1% vs 1.2%; p = 0.005). CONCLUSION: Patient portal messages inviting seniors to participate in a randomized controlled trial resulted in a response rate similar to commercial email marketing and resulted in very few complaints or opt-out requests. Furthermore, a longer message with more content enhanced response rate. Recruitment through patient portals might be an effective strategy to enroll trial participants.

Alcohol Consumption and Incident Kidney Disease: Results From the Atherosclerosis Risk in Communities Study.

OBJECTIVE(S): Moderate alcohol consumption has been found to be associated with lower risk of coronary heart disease and myocardial infarction, which share similar risk factors and pathophysiology with chronic kidney disease (CKD). However, there is inconsistent evidence on the association between alcohol consumption and CKD. DESIGN AND METHODS: We conducted a prospective analysis of 12,692 participants aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study. We categorized participants into 6 alcohol consumption categories: never drinkers, former drinkers, ≤1 drink per week, 2 to 7 drinks per week, 8 to 14 drinks per week, and ≥15 drinks per week based on food frequency questionnaire responses at visit 1 (1987-1989). Incident CKD was defined as estimated glomerular filtration rate <60 mL/minute/1.73 m2 accompanied by ≥25% estimated glomerular filtration rate decline, a kidney disease-related hospitalization or death or end-stage renal disease. RESULTS: During a median follow-up of 24 years, there were 3,664 cases of incident CKD. Current drinkers were more likely to be men, whites, and to have a higher income level and education level. After adjusting for total energy intake, age, sex, race-center, income, education level, health insurance, smoking, and physical activity, there was no significant association between being a former drinker and risk of incident CKD. Participants who drank ≤1 drink per week, 2 to 7 drinks per week, 8 to 14 drinks per week, and ≥15 drinks per week had, respectively, a 12% (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.79-0.97), 20% (HR: 0.80, 95% CI: 0.72-0.89), 29% (HR: 0.71, 95% CI: 0.62-0.83), and 23% (HR: 0.77, 95% CI: 0.65-0.91) lower risk of CKD compared with never drinkers. CONCLUSION(S): Consuming a low or moderate amount of alcohol may lower the risk of developing CKD. Therefore, moderate consumption of alcohol may not likely be harmful to the kidneys.

Alcohol consumption and incident diabetes: The Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the prospective association between baseline and 9 year change in alcohol consumption and long-term risk of diabetes and whether these associations might be modified by sex and/or BMI. METHODS: We conducted a prospective analysis of 12,042 Atherosclerosis Risk in Communities (ARIC) study participants without prevalent diabetes (55% women, 78% white, mean age 54 years). Alcohol consumption was assessed at visit 1 (1987-1989) and visit 4 (1996-1998). We used Cox models to estimate hazard ratios for diabetes risk by baseline drinking categories and change in alcohol consumption, stratified by sex and obesity status. RESULTS: During a median follow-up of 21 years, there were 3795 incident cases of diabetes. Among women, consuming 8-14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.75, 95% CI 0.58, 0.96) compared with current drinkers consuming ≤1 drink/week. Among men, consuming 8-14 drinks/week was associated with a borderline significant lower risk of diabetes (HR 0.84, 95% CI 0.70, 1.00) and consuming >14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.81, 95% CI 0.67, 0.97) (pinteraction < 0.01 for sex). For both sexes, among current drinkers, there was a significant decreasing trend in diabetes risk as the alcohol consumption increased. The association was modified by BMI (pinteraction = 0.042 for women, pinteraction < 0.001 for men). In women, the inverse association was only seen among overweight and obese participants. In men, the inverse association was more pronounced among obese participants. On average, drinking status did not change substantially over the 9 year period. For men with alcohol intake ≥7 drinks/week at baseline, decreasing alcohol intake was associated with higher risk of diabetes (HR per daily drink decrease 1.12, 95% CI 1.02, 1.23). CONCLUSIONS/INTERPRETATION: In this community-based population, there was an inverse association between alcohol consumption and diabetes risk. The amount of the alcohol consumption associated with lower risk was different in women and men, and the association was more pronounced among participants with higher BMI.

Fasting Versus Nonfasting and Low-Density Lipoprotein Cholesterol Accuracy.

BACKGROUND: Recent recommendations favoring nonfasting lipid assessment may affect low-density lipoprotein cholesterol (LDL-C) estimation. The novel method of LDL-C estimation (LDL-CN) uses a flexible approach to derive patient-specific ratios of triglycerides to very low-density lipoprotein cholesterol. This adaptability may confer an accuracy advantage in nonfasting patients over the fixed approach of the classic Friedewald method (LDL-CF). METHODS: We used a US cross-sectional sample of 1 545 634 patients (959 153 fasting ≥10-12 hours; 586 481 nonfasting) from the second harvest of the Very Large Database of Lipids study to assess for the first time the impact of fasting status on novel LDL-C accuracy. Rapid ultracentrifugation was used to directly measure LDL-C content (LDL-CD). Accuracy was defined as the percentage of LDL-CD falling within an estimated LDL-C (LDL-CN or LDL-CF) category by clinical cut points. For low estimated LDL-C (<70 mg/dL), we evaluated accuracy by triglyceride levels. The magnitude of absolute and percent differences between LDL-CD and estimated LDL-C (LDL-CN or LDL-CF) was stratified by LDL-C and triglyceride categories. RESULTS: In both fasting and nonfasting samples, accuracy was higher with the novel method across all clinical LDL-C categories (range, 87%-94%) compared with the Friedewald estimation (range, 71%-93%; P≤0.001). With LDL-C <70 mg/dL, nonfasting LDL-CN accuracy (92%) was superior to LDL-CF accuracy (71%; P<0.001). In this LDL-C range, 19% of fasting and 30% of nonfasting patients had differences ≥10 mg/dL between LDL-CF and LDL-CD, whereas only 2% and 3% of patients, respectively, had similar differences with novel estimation. Accuracy of LDL-C <70 mg/dL further decreased as triglycerides increased, particularly for Friedewald estimation (range, 37%-96%) versus the novel method (range, 82%-94%). With triglycerides of 200 to 399 mg/dL in nonfasting patients, LDL-CN <70 mg/dL accuracy (82%) was superior to LDL-CF (37%; P<0.001). In this triglyceride range, 73% of fasting and 81% of nonfasting patients had ≥10 mg/dL differences between LDL-CF and LDL-CD compared with 25% and 20% of patients, respectively, with LDL-CN. CONCLUSIONS: Novel adaptable LDL-C estimation performs better in nonfasting samples than the fixed Friedewald estimation, with a particular accuracy advantage in settings of low LDL-C and high triglycerides. In addition to stimulating further study, these results may have immediate relevance for guideline committees, laboratory leadership, clinicians, and patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01698489.

Six-Year Changes in Physical Activity and the Risk of Incident Heart Failure: ARIC Study.

BACKGROUND: Higher physical activity (PA) is associated with lower heart failure (HF) risk; however, the effect of changes in PA on HF risk is unknown. METHODS: We evaluated 11 351 ARIC study (Atherosclerosis Risk in Communities) participants (mean age 60 years) who attended visit 3 (1993-1995) and did not have a history of cardiovascular disease. Exercise PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines as recommended, intermediate, or poor. We used Cox regression models to characterize the association of 6-year changes in PA between the first (1987-1989) and third ARIC visits and HF risk. RESULTS: During a median of 19 years of follow-up, 1750 HF events occurred. Compared with those with poor activity at both visits, the lowest HF risk was seen for those with persistently recommended activity (hazard ratio, 0.69; 95% confidence interval, 0.60-0.80). However, those whose PA increased from poor to recommended also had reduced HF risk (hazard ratio, 0.77; 95% confidence interval 0.63-0.93). Among participants with poor baseline activity, each 1 SD higher PA at 6 years (512.5 METS*minutes/week, corresponding to ≈30 minutes of brisk walking 4 times per week) was associated with significantly lower future HF risk (hazard ratio, 0.89, 95% confidence interval, 0.82-0.96). CONCLUSIONS: Although maintaining recommended activity levels is associated with the lowest HF risk, initiating and increasing PA, even in late middle age, are also linked to lower HF risk. Augmenting PA may be an important component of strategies to prevent HF.

Economic Insecurity and Deaths of Despair in US Counties.

Recent research has implicated economic insecurity in increasing midlife death rates and "deaths of despair," including suicide, chronic liver disease, and drug and alcohol poisoning. In this ecological longitudinal study, we evaluated the association between changes in economic insecurity and increases in deaths of despair and midlife all-cause mortality in US counties during 2000-2015. We extended a previously developed measure of economic insecurity using indicators from the Census and Federal Reserve Bank in US counties for the years 2000 and 2010. Linear regression models were used to estimate the association of change in economic insecurity with change in death rates through 2015. Counties experiencing elevated economic insecurity in either 2000 or 2010 had higher rates of deaths of despair and all-cause midlife mortality at baseline but similar rates of increase in deaths of despair from 2001 to 2015 compared with counties with stable low economic insecurity. Counties in the highest tertile of economic insecurity in 2000 and 2010 had 41% (95% confidence interval: 1.36, 1.47) higher midlife mortality rates at baseline and a rate of increase of 2% more per 5-year period (95% confidence interval: 1.00, 1.03) than counties with stable low economic insecurity. Economic insecurity may represent a population-level driver of US death trends.