Peter Ueda

Hypertension, diabetes and overweight: looming legacies of the Biafran famine.

Background Sub-Saharan Africa is facing rapidly increasing prevalences of cardiovascular disease, obesity, diabetes and hypertension. Previous and ongoing undernutrition among pregnant women may contribute to this development as suggested by epidemiological studies from high income countries linking undernutrition in fetal life with increased burden of non-communicable diseases in later life. We undertook to study the risks for hypertension, glucose intolerance and overweight forty years after fetal exposure to famine afflicted Biafra during the Nigerian civil war (1967–1970). Methods and Findings Cohort study performed in June 27–July 31, 2009 in Enugu, Nigeria. Adults (n = 1,339) born before (1965–67), during (1968–January 1970), or after (1971–73) the years of famine were included. Blood pressure (BP), random plasma glucose (p-glucose) and anthropometrics, as well as prevalence of hypertension (BP>140/90 mmHg), impaired glucose tolerance (IGT; p-glucose 7.8–11.0 mmol/l), diabetes (DM; p-glucose ≥11.1 mmol/l), or overweight (BMI>25 kg/m2) were compared between the three groups. Fetal-infant exposure to famine was associated with elevated systolic (+7 mmHg; p<0.001) and diastolic (+5 mmHg; p<0.001) BP, increased p-glucose (+0.3 mmol/L; p<0.05) and waist circumference (+3cm, p<0.001), increased risk of systolic hypertension (adjusted OR 2.87; 95% CI 1.90–4.34), IGT (OR 1.65; 95% CI 1.02–2.69) and overweight (OR 1.41; 95% CI 1.03–1.93) as compared to people born after the famine. Limitations of this study include the lack of birth weight data and the inability to separate effects of fetal and infant famine. Conclusions Fetal and infant undernutrition is associated with significantly increased risk of hypertension and impaired glucose tolerance in 40-year-old Nigerians. Prevention of undernutrition during pregnancy and in infancy should therefore be given high priority in health, education, and economic agendas.

A novel risk score to predict cardiovascular disease risk in national populations (Globorisk): a pooled analysis of prospective cohorts and health examination surveys

BACKGROUND Treatment of cardiovascular risk factors based on disease risk depends on valid risk prediction equations. We aimed to develop, and apply in example countries, a risk prediction equation for cardiovascular disease (consisting here of coronary heart disease and stroke) that can be recalibrated and updated for application in different countries with routinely available information. METHODS We used data from eight prospective cohort studies to estimate coefficients of the risk equation with proportional hazard regressions. The risk prediction equation included smoking, blood pressure, diabetes, and total cholesterol, and allowed the effects of sex and age on cardiovascular disease to vary between cohorts or countries. We developed risk equations for fatal cardiovascular disease and for fatal plus non-fatal cardiovascular disease. We validated the risk equations internally and also using data from three cohorts that were not used to create the equations. We then used the risk prediction equation and data from recent (2006 or later) national health surveys to estimate the proportion of the population at different levels of cardiovascular disease risk in 11 countries from different world regions (China, Czech Republic, Denmark, England, Iran, Japan, Malawi, Mexico, South Korea, Spain, and USA). FINDINGS The risk score discriminated well in internal and external validations, with C statistics generally 70% or more. At any age and risk factor level, the estimated 10 year fatal cardiovascular disease risk varied substantially between countries. The prevalence of people at high risk of fatal cardiovascular disease was lowest in South Korea, Spain, and Denmark, where only 5-10% of men and women had more than a 10% risk, and 62-77% of men and 79-82% of women had less than a 3% risk. Conversely, the proportion of people at high risk of fatal cardiovascular disease was largest in China and Mexico. In China, 33% of men and 28% of women had a 10-year risk of fatal cardiovascular disease of 10% or more, whereas in Mexico, the prevalence of this high risk was 16% for men and 11% for women. The prevalence of less than a 3% risk was 37% for men and 42% for women in China, and 55% for men and 69% for women in Mexico. INTERPRETATION We developed a cardiovascular disease risk equation that can be recalibrated for application in different countries with routinely available information. The estimated percentage of people at high risk of fatal cardiovascular disease was higher in low-income and middle-income countries than in high-income countries. FUNDING US National Institutes of Health, UK Medical Research Council, Wellcome Trust.

Gotta catch’em all! Pokémon GO and physical activity among young adults: difference in differences study

Objective To estimate the effect of playing Pokémon GO on the number of steps taken daily up to six weeks after installation of the game. Design Cohort study using online survey data. Participants Survey participants of Amazon Mechanical Turk (n=1182) residing in the United States, aged 18 to 35 years and using iPhone 6 series smartphones. Main outcome measures Number of daily steps taken each of the four weeks before and six weeks after installation of Pokémon GO, automatically recorded in the “Health” application of the iPhone 6 series smartphones and reported by the participants. A difference in difference regression model was used to estimate the change in daily steps in players of Pokémon GO compared with non-players. Results 560 (47.4%) of the survey participants reported playing Pokémon GO and walked on average 4256 steps (SD 2697) each day in the four weeks before installation of the game. The difference in difference analysis showed that the daily average steps for Pokémon GO players during the first week of installation increased by 955 additional steps (95% confidence interval 697 to 1213), and then this increase gradually attenuated over the subsequent five weeks. By the sixth week after installation, the number of daily steps had gone back to pre-installation levels. No significant effect modification of Pokémon GO was found by sex, age, race group, bodyweight status, urbanity, or walkability of the area of residence. Conclusions Pokémon GO was associated with an increase in the daily number of steps after installation of the game. The association was, however, moderate and no longer observed after six weeks.

Neonatal vitamin D status and risk of multiple sclerosis

Low vitamin D status at birth may be associated with risk of adult onset multiple sclerosis, but this link has not been studied directly. We assessed the relation between neonatal vitamin D concentrations, measured in stored blood samples, and risk of multiple sclerosis.

Season of birth, neonatal vitamin D status, and cardiovascular disease risk at 35 y of age: a cohort study from Sweden

BACKGROUND Lower vitamin D status during gestation may be associated with cardiovascular disease risk later in life. No studies have assessed this hypothesis with a follow-up time reaching beyond childhood. OBJECTIVE The objective was to assess the link between season of birth, neonatal 25-hydroxyvitamin D₃ [25(OH)D₃] status, and adult cardiovascular disease risk. DESIGN Markers of cardiovascular and metabolic disease risk were measured in 284 subjects aged 35 y, born either at the end of the winter or at the end of the summer of 1975. In 275 of these 284 subjects, concentrations of neonatal 25(OH)D₃ were measured in dried blood samples by using a highly sensitive liquid chromatography-tandem mass spectroscopy method. RESULTS Subjects born after the winter had lower neonatal 25(OH)D₃ concentrations than did those born after the summer (31.5 compared with 48.5 nmol/L; P < 0.001). In regression analyses adjusted for sex, season of birth, postnatal age at neonatal sample collection, preterm birth, maternal age, education, smoking, fish consumption per week, exercise per week, and current 25-hydroxyvitamin D, higher neonatal 25(OH)D₃ (per 50 nmol/L) was associated with 25.8% (95% CI: 1.0%, 58.4%) higher fasting insulin in adult life, 29.6% (5.1%, 58.4%) higher triglycerides, and 4.64 (95% CI: 1.93, 7.36) mmol/L higher serum cholesterol in women. Neonatal 25(OH)D₃ (per 1 nmol/L) was directly associated with risk of adult overweight (OR: 1.03; 95% CI: 1.01, 1.05) and with adult obesity in women (OR: 1.09; 95% CI: 1.02, 1.17). Neonatal 25(OH)D₃ was not associated with adult aortic pulse wave velocity, blood pressure, fasting glucose, HDL, LDL, or C-reactive protein. Season of birth was not associated with any of the adult outcomes. CONCLUSIONS Higher neonatal 25(OH)D₃ was associated with higher fasting insulin, triglyceride, and cholesterol (in women) concentrations and with a higher risk of overweight at 35 y of age but not with other adult cardiovascular disease risk factors.

Food marketing towards children: brand logo recognition, food-related behavior and BMI among 3-13-year-olds in a south Indian town.

Objectives To assess exposure to marketing of unhealthy food products and its relation to food related behavior and BMI in children aged 3–13, from different socioeconomic backgrounds in a south Indian town. Methods Child-parent pairs (n = 306) were recruited at pediatric clinics. Exposure to food marketing was assessed by a digital logo recognition test. Children matched 18 logos of unhealthy food (high in fat/sugar/salt) featured in promotion material from the food industry to pictures of corresponding products. Childrens nutritional knowledge, food preferences, purchase requests, eating behavior and socioeconomic characteristics were assessed by a digital game and parental questionnaires. Anthropometric measurements were recorded. Results Recognition rates for the brand logos ranged from 30% to 80%. Logo recognition ability increased with age (p<0.001) and socioeconomic level (p<0.001 comparing children in the highest and lowest of three socioeconomic groups). Adjusted for gender, age and socioeconomic group, logo recognition was associated with higher BMI (p = 0.022) and nutritional knowledge (p<0.001) but not to unhealthy food preferences or purchase requests. Conclusions Children from higher socioeconomic groups in the region had higher brand logo recognition ability and are possibly exposed to more food marketing. The study did not lend support to a link between exposure to marketing and poor eating behavior, distorted nutritional knowledge or increased purchase requests. The correlation between logo recognition and BMI warrants further investigation on food marketing towards children and its potential role in the increasing burden of non-communicable diseases in this part of India.

Month of Birth and Mortality in Sweden: A Nation-Wide Population-Based Cohort Study

Background Month of birth – an indicator for a variety of prenatal and early postnatal exposures – has been associated with life expectancy in adulthood. On the northern hemisphere, people born in the autumn live longer than those born during the spring. Only one study has followed a population longitudinally and no study has investigated the relation between month of birth and mortality risk below 50 years. Methods and results In this nation-wide Swedish study, we included 6,194,745 subjects, using data from population-based health and administrative registries. The relation between month of birth (January – December) and mortality risk was assessed by fitting Cox proportional hazard regression models using attained age as the underlying time scale. Analyses were made for ages >30, >30 to 50, >50 to 80 and >80 years. Month of birth was a significant predictor of mortality in the age-spans >30, >50 to 80, and >80 years. In models adjusted for gender and education for ages >30 and >50 to 80 years, the lowest mortality was seen for people born in November and the highest mortality in those born in the spring/summer, peaking in May for mortality >30 years (25‰ excess hazard ratio compared to November, [95% confidence interval = 16–34 ]) and in April for mortality >50 to 80 years (42‰ excess hazard ratio compared to November, [95% confidence interval = 30–55]). In the ages >80 years the pattern was similar but the differences in mortality between birth months were smaller. For mortality within the age-span >30 to 50 years, results were inconclusive. Conclusion Month of birth is associated to risk of mortality in ages above 50 years in Sweden. Further studies should aim at clarifying the mechanisms behind this association.

Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys.

BACKGROUND Worldwide implementation of risk-based cardiovascular disease (CVD) prevention requires risk prediction tools that are contemporarily recalibrated for the target country and can be used where laboratory measurements are unavailable. We present two cardiovascular risk scores, with and without laboratory-based measurements, and the corresponding risk charts for 182 countries to predict 10-year risk of fatal and non-fatal CVD in adults aged 40-74 years. METHODS Based on our previous laboratory-based prediction model (Globorisk), we used data from eight prospective studies to estimate coefficients of the risk equations using proportional hazard regressions. The laboratory-based risk score included age, sex, smoking, blood pressure, diabetes, and total cholesterol; in the non-laboratory (office-based) risk score, we replaced diabetes and total cholesterol with BMI. We recalibrated risk scores for each sex and age group in each country using country-specific mean risk factor levels and CVD rates. We used recalibrated risk scores and data from national surveys (using data from adults aged 40-64 years) to estimate the proportion of the population at different levels of CVD risk for ten countries from different world regions as examples of the information the risk scores provide; we applied a risk threshold for high risk of at least 10% for high-income countries (HICs) and at least 20% for low-income and middle-income countries (LMICs) on the basis of national and international guidelines for CVD prevention. We estimated the proportion of men and women who were similarly categorised as high risk or low risk by the two risk scores. FINDINGS Predicted risks for the same risk factor profile were generally lower in HICs than in LMICs, with the highest risks in countries in central and southeast Asia and eastern Europe, including China and Russia. In HICs, the proportion of people aged 40-64 years at high risk of CVD ranged from 1% for South Korean women to 42% for Czech men (using a ≥10% risk threshold), and in low-income countries ranged from 2% in Uganda (men and women) to 13% in Iranian men (using a ≥20% risk threshold). More than 80% of adults were similarly classified as low or high risk by the laboratory-based and office-based risk scores. However, the office-based model substantially underestimated the risk among patients with diabetes. INTERPRETATION Our risk charts provide risk assessment tools that are recalibrated for each country and make the estimation of CVD risk possible without using laboratory-based measurements. FUNDING National Institutes of Health.

Application of the 2014 NICE cholesterol guidelines in the English population: a cross-sectional analysis.

BACKGROUND The 2014 guidelines on cardiovascular risk assessment and lipid modification from the National Institute for Health and Care Excellence (NICE) recommend statin therapy for adults with prevalent cardiovascular disease (CVD), and for adults with a 10-year CVD risk of ≥10%, estimated using the QRISK2 algorithm. AIM To determine risk factor levels required to exceed the risk threshold for statin therapy, and to estimate the number of adults in England who would require statin therapy under the guidelines. DESIGN AND SETTING Cross-sectional study using a sample representative of the English population aged 30-84 years. METHOD To estimate 10-year CVD risk different combinations of risk factor levels were entered into the QRISK2 algorithm. The NICE guidelines were applied to the sample using data from the Health Survey for England 2011. RESULTS Even with optimal risk factor levels, males of different ethnicities would exceed the 10% risk threshold between the ages of 60 and 70 years, and females would exceed the threshold between 65 and 75 years. Under the NICE guidelines, 11.8 million males and females (37% of the adults aged 30-84 years) would require statin therapy, most of them (9.8 million) for primary prevention. When analysed by age, 95% of males and 66% of females without CVD in ages 60-74 years, including all males and females in ages 75-84 years, would require statin therapy. CONCLUSION Under the 2014 NICE guidelines, 11.8 million (37%) adults in England aged 30-84 years, including almost all males >60 years in all females >75 years, require statin therapy.

Sick Populations and Sick Subpopulations: Reducing Disparities in Cardiovascular Disease Between Blacks and Whites in the United States

Background: Cardiovascular disease (CVD) death rates are much higher in blacks than whites in the United States. It is unclear how CVD risk and events are distributed among blacks versus whites and how interventions reduce racial disparities. Methods: We developed risk models for fatal and for fatal and nonfatal CVD using 8 cohorts in the United States. We used 6154 adults who were 50 to 69 years of age in the National Health and Nutrition Examination Survey 1999 to 2012 to estimate the distributions of risk and events in blacks and whites. We estimated the total and disparity impacts of a range of population-wide, targeted, and risk-based interventions on 10-year CVD risks and event rates. Results: Twenty-five percent (95% confidence interval [CI], 22–28) of black men and 12% (95% CI, 10–14) of black women were at ≥6.67% risk of fatal CVD (almost equivalent to 20% risk of fatal or nonfatal CVD) compared with 10% (95% CI, 8–12) of white men and 3% (95% CI, 2–4) of white women. These high-risk individuals accounted for 55% (95% CI, 49–59) of CVD deaths among black men and 42% (95% CI, 35–46) in black women compared with 30% (95% CI, 24–35) in white men and 18% (95% CI, 13–22) in white women. We estimated that an intervention that treated multiple risk factors in high-risk individuals could reduce black-white difference in CVD death rate from 1659 to 1244 per 100 000 in men and from 1320 to 897 in women. Rates of fatal and nonfatal CVD were generally similar between black and white men. In women, a larger proportion of women were at ≥7.5% risk of CVD (30% versus 19% in whites), and an intervention that targeted multiple risk factors among this group was estimated to reduce black-white differences in CVD rates from 1688 to 1197 per 100 000. Conclusions: A substantially larger proportion of blacks have a high risk of fatal CVD and bear a large share of CVD deaths. A risk-based intervention that reduces multiple risk factors could substantially reduce overall CVD rates and racial disparities in CVD death rates.