Independent role of Alzheimer's disease genetics and C-reactive protein on cognitive ability in aging.

Apolipoprotein E (APOE) ε4, the strongest genetic risk factor for late onset Alzheimer's disease (LOAD), has been associated with cognitive decline independent from AD pathology, but the role for other LOAD risk genes in normal cognitive aging is less studied. We examined the effect of APOE ε4 and several different polygenic risk scores (PRS) for LOAD on cognitive level and decline in aging, using longitudinal data from the UK Biobank. While PRS-LOAD including all variants (except APOE) predicted cognitive level, APOE ε4 and PRS-LOAD based on 17 non-APOE gene variants with strong association to AD (p < 5e-8) predicted age-related decline in verbal numeric reasoning. The effect on decline were partly driven by 4 variants involved in the immune system. Those variants also predicted serum levels of the inflammatory marker C-reactive protein (CRP), but CRP did not mediate the effect on decline. Those findings suggest genetic variations in immune functions play a role in aspects of cognitive aging that may be independent of LOAD pathology as well as systemic inflammation measured by CRP.

Cardiovascular disease risk profile and management practices in 45 low-income and middle-income countries: A cross-sectional study of nationally representative individual-level survey data.

BACKGROUND: Global cardiovascular disease (CVD) burden is high and rising, especially in low-income and middle-income countries (LMICs). Focussing on 45 LMICs, we aimed to determine (1) the adult population's median 10-year predicted CVD risk, including its variation within countries by socio-demographic characteristics, and (2) the prevalence of self-reported blood pressure (BP) medication use among those with and without an indication for such medication as per World Health Organization (WHO) guidelines. METHODS AND FINDINGS: We conducted a cross-sectional analysis of nationally representative household surveys from 45 LMICs carried out between 2005 and 2017, with 32 surveys being WHO Stepwise Approach to Surveillance (STEPS) surveys. Country-specific median 10-year CVD risk was calculated using the 2019 WHO CVD Risk Chart Working Group non-laboratory-based equations. BP medication indications were based on the WHO Package of Essential Noncommunicable Disease Interventions guidelines. Regression models examined associations between CVD risk, BP medication use, and socio-demographic characteristics. Our complete case analysis included 600,484 adults from 45 countries. Median 10-year CVD risk (interquartile range [IQR]) for males and females was 2.7% (2.3%-4.2%) and 1.6% (1.3%-2.1%), respectively, with estimates indicating the lowest risk in sub-Saharan Africa and highest in Europe and the Eastern Mediterranean. Higher educational attainment and current employment were associated with lower CVD risk in most countries. Of those indicated for BP medication, the median (IQR) percentage taking medication was 24.2% (15.4%-37.2%) for males and 41.6% (23.9%-53.8%) for females. Conversely, a median (IQR) 47.1% (36.1%-58.6%) of all people taking a BP medication were not indicated for such based on CVD risk status. There was no association between BP medication use and socio-demographic characteristics in most of the 45 study countries. Study limitations include variation in country survey methods, most notably the sample age range and year of data collection, insufficient data to use the laboratory-based CVD risk equations, and an inability to determine past history of a CVD diagnosis. CONCLUSIONS: This study found underuse of guideline-indicated BP medication in people with elevated CVD risk and overuse by people with lower CVD risk. Country-specific targeted policies are needed to help improve the identification and management of those at highest CVD risk.

Association between country preparedness indicators and quality clinical care for cardiovascular disease risk factors in 44 lower- and middle-income countries: A multicountry analysis of survey data.

BACKGROUND: Cardiovascular diseases are leading causes of death, globally, and health systems that deliver quality clinical care are needed to manage an increasing number of people with risk factors for these diseases. Indicators of preparedness of countries to manage cardiovascular disease risk factors (CVDRFs) are regularly collected by ministries of health and global health agencies. We aimed to assess whether these indicators are associated with patient receipt of quality clinical care. METHODS AND FINDINGS: We did a secondary analysis of cross-sectional, nationally representative, individual-patient data from 187,552 people with hypertension (mean age 48.1 years, 53.5% female) living in 43 low- and middle-income countries (LMICs) and 40,795 people with diabetes (mean age 52.2 years, 57.7% female) living in 28 LMICs on progress through cascades of care (condition diagnosed, treated, or controlled) for diabetes or hypertension, to indicate outcomes of provision of quality clinical care. Data were extracted from national-level World Health Organization (WHO) Stepwise Approach to Surveillance (STEPS), or other similar household surveys, conducted between July 2005 and November 2016. We used mixed-effects logistic regression to estimate associations between each quality clinical care outcome and indicators of country development (gross domestic product [GDP] per capita or Human Development Index [HDI]); national capacity for the prevention and control of noncommunicable diseases ('NCD readiness indicators' from surveys done by WHO); health system finance (domestic government expenditure on health [as percentage of GDP], private, and out-of-pocket expenditure on health [both as percentage of current]); and health service readiness (number of physicians, nurses, or hospital beds per 1,000 people) and performance (neonatal mortality rate). All models were adjusted for individual-level predictors including age, sex, and education. In an exploratory analysis, we tested whether national-level data on facility preparedness for diabetes were positively associated with outcomes. Associations were inconsistent between indicators and quality clinical care outcomes. For hypertension, GDP and HDI were both positively associated with each outcome. Of the 33 relationships tested between NCD readiness indicators and outcomes, only two showed a significant positive association: presence of guidelines with being diagnosed (odds ratio [OR], 1.86 [95% CI 1.08-3.21], p = 0.03) and availability of funding with being controlled (OR, 2.26 [95% CI 1.09-4.69], p = 0.03). Hospital beds (OR, 1.14 [95% CI 1.02-1.27], p = 0.02), nurses/midwives (OR, 1.24 [95% CI 1.06-1.44], p = 0.006), and physicians (OR, 1.21 [95% CI 1.11-1.32], p < 0.001) per 1,000 people were positively associated with being diagnosed and, similarly, with being treated; and the number of physicians was additionally associated with being controlled (OR, 1.12 [95% CI 1.01-1.23], p = 0.03). For diabetes, no positive associations were seen between NCD readiness indicators and outcomes. There was no association between country development, health service finance, or health service performance and readiness indicators and any outcome, apart from GDP (OR, 1.70 [95% CI 1.12-2.59], p = 0.01), HDI (OR, 1.21 [95% CI 1.01-1.44], p = 0.04), and number of physicians per 1,000 people (OR, 1.28 [95% CI 1.09-1.51], p = 0.003), which were associated with being diagnosed. Six countries had data on cascades of care and nationwide-level data on facility preparedness. Of the 27 associations tested between facility preparedness indicators and outcomes, the only association that was significant was having metformin available, which was positively associated with treatment (OR, 1.35 [95% CI 1.01-1.81], p = 0.04). The main limitation was use of blood pressure measurement on a single occasion to diagnose hypertension and a single blood glucose measurement to diagnose diabetes. CONCLUSION: In this study, we observed that indicators of country preparedness to deal with CVDRFs are poor proxies for quality clinical care received by patients for hypertension and diabetes. The major implication is that assessments of countries' preparedness to manage CVDRFs should not rely on proxies; rather, it should involve direct assessment of quality clinical care.

The state of hypertension care in 44 low-income and middle-income countries: a cross-sectional study of nationally representative individual-level data from 1·1 million adults.

BACKGROUND: Evidence from nationally representative studies in low-income and middle-income countries (LMICs) on where in the hypertension care continuum patients are lost to care is sparse. This information, however, is essential for effective targeting of interventions by health services and monitoring progress in improving hypertension care. We aimed to determine the cascade of hypertension care in 44 LMICs-and its variation between countries and population groups-by dividing the progression in the care process, from need of care to successful treatment, into discrete stages and measuring the losses at each stage. METHODS: In this cross-sectional study, we pooled individual-level population-based data from 44 LMICs. We first searched for nationally representative datasets from the WHO Stepwise Approach to Surveillance (STEPS) from 2005 or later. If a STEPS dataset was not available for a LMIC (or we could not gain access to it), we conducted a systematic search for survey datasets; the inclusion criteria in these searches were that the survey was done in 2005 or later, was nationally representative for at least three 10-year age groups older than 15 years, included measured blood pressure data, and contained data on at least two hypertension care cascade steps. Hypertension was defined as a systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or reported use of medication for hypertension. Among those with hypertension, we calculated the proportion of individuals who had ever had their blood pressure measured; had been diagnosed with hypertension; had been treated for hypertension; and had achieved control of their hypertension. We weighted countries proportionally to their population size when determining this hypertension care cascade at the global and regional level. We disaggregated the hypertension care cascade by age, sex, education, household wealth quintile, body-mass index, smoking status, country, and region. We used linear regression to predict, separately for each cascade step, a country's performance based on gross domestic product (GDP) per capita, allowing us to identify countries whose performance fell outside of the 95% prediction interval. FINDINGS: Our pooled dataset included 1 100 507 participants, of whom 192 441 (17·5%) had hypertension. Among those with hypertension, 73·6% of participants (95% CI 72·9-74·3) had ever had their blood pressure measured, 39·2% of participants (38·2-40·3) had been diagnosed with hypertension, 29·9% of participants (28·6-31·3) received treatment, and 10·3% of participants (9·6-11·0) achieved control of their hypertension. Countries in Latin America and the Caribbean generally achieved the best performance relative to their predicted performance based on GDP per capita, whereas countries in sub-Saharan Africa performed worst. Bangladesh, Brazil, Costa Rica, Ecuador, Kyrgyzstan, and Peru performed significantly better on all care cascade steps than predicted based on GDP per capita. Being a woman, older, more educated, wealthier, and not being a current smoker were all positively associated with attaining each of the four steps of the care cascade. INTERPRETATION: Our study provides important evidence for the design and targeting of health policies and service interventions for hypertension in LMICs. We show at what steps and for whom there are gaps in the hypertension care process in each of the 44 countries in our study. We also identified countries in each world region that perform better than expected from their economic development, which can direct policy makers to important policy lessons. Given the high disease burden caused by hypertension in LMICs, nationally representative hypertension care cascades, as constructed in this study, are an important measure of progress towards achieving universal health coverage. FUNDING: Harvard McLennan Family Fund, Alexander von Humboldt Foundation.

Consumption of Fruits and Vegetables Among Individuals 15 Years and Older in 28 Low- and Middle-Income Countries.

BACKGROUND: The WHO recommends 400 g/d of fruits and vegetables (the equivalent of ∼5 servings/d) for the prevention of noncommunicable diseases (NCDs). However, there is limited evidence regarding individual-level correlates of meeting these recommendations in low- and middle-income countries (LMICs). In order to target policies and interventions aimed at improving intake, global monitoring of fruit and vegetable consumption by socio-demographic subpopulations is required. OBJECTIVES: The aims of this study were to 1) assess the proportion of individuals meeting the WHO recommendation and 2) evaluate socio-demographic predictors (age, sex, and educational attainment) of meeting the WHO recommendation. METHODS: Data were collected from 193,606 individuals aged ≥15 y in 28 LMICs between 2005 and 2016. The prevalence of meeting the WHO recommendation took into account the complex survey designs, and countries were weighted according to their World Bank population estimates in 2015. Poisson regression was used to estimate associations with socio-demographic characteristics. RESULTS: The proportion (95% CI) of individuals aged ≥15 y who met the WHO recommendation was 18.0% (16.6-19.4%). Mean intake of fruits was 1.15 (1.10-1.20) servings per day and for vegetables, 2.46 (2.40-2.51) servings/d. The proportion of individuals meeting the recommendation increased with increasing country gross domestic product (GDP) class (P < 0.0001) and with decreasing country FAO food price index (FPI; indicating greater stability of food prices; P < 0.0001). At the individual level, those with secondary education or greater were more likely to achieve the recommendation compared with individuals with no formal education: risk ratio (95% CI), 1.61 (1.24-2.09). CONCLUSIONS: Over 80% of individuals aged ≥15 y living in these 28 LMICs consumed lower amounts of fruits and vegetables than recommended by the WHO. Policies to promote fruit and vegetable consumption in LMICs are urgently needed to address the observed inequities in intake and prevent NCDs.

Prevalence, awareness, treatment and control of dyslipidemia in older persons in urban and rural population in the Astana region, Kazakhstan.

BACKGROUND: Despite high cardiovascular mortality in Central Asian republics of the former Soviet Union, there is limited information about major risk factors, including blood lipids. We investigated the prevalence of impaired concentrations of blood lipids, the awareness, treatment and control of hypercholesterolemia, and factors associated with these indicators in urban and rural populations in Kazakhstan. METHODS: We conducted a cross-sectional study of random urban and rural population samples (the state capital Astana and Akmol village). Men and women aged 50-74 years were examined; a total of 954 adults participated (response rate 59%). Serum concentrations of total, LDL and HDL cholesterol and triglycerides and a range of other cardiovascular risk factors were measured. RESULTS: The overall prevalence of hypercholesterolemia (total cholesterol ≥6.2 mmol/l) was 37%; among subjects with hypercholesterolemia, 57% were aware of their condition, 41% took medication and 23% had total cholesterol <6.2 mmol/l (4.5% <5 mmol/l). The prevalence, awareness, treatment, and control of hypercholesterolemia were all higher in the urban than the rural area. Similarly, the proportions of subjects with impaired concentrations of specific lipids fractions were also considerably higher in the urban population. Most associations with other covariates were in the expected direction. CONCLUSIONS: This study found relatively high prevalence of dyslipidemia in the Kazakh population, and the blood lipid profile was less favourable in the urban area. These pronounced urban-rural differences may be related to urbanization, the associated nutrition transition and to access to health care.

Diabetes prevalence, awareness and treatment and their correlates in older persons in urban and rural population in the Astana region, Kazakhstan.

AIMS: The evidence on the prevalence and distribution of diabetes and its determinants in Central Asia is sparse. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of diabetes and factors associated with these characteristics in the population of Astana (capital) city and adjacent rural area in Kazakhstan. METHODS: Participants aged 50-75 years old, residing in Astana city (the capital) and Akmol village were invited to participate in a cross-sectional study. The subjects were randomly selected from polyclinic registers. A total of 953 adults were interviewed (response rate 59%), and their fasting plasma glucose, blood pressure, height and weight were measured. Diabetes was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/l (126 mg/dl) and/or being on diabetes medication. RESULTS: The overall prevalence of diabetes was 12.5%, and it was almost twice higher in the urban residents (16.3%) than in the rural population (8.6%). Diabetes prevalence was associated with age, men sex, hypertension, obesity, and Russian ethnicity. Among subjects with diabetes, 72.3% were aware of their condition; 65.6% were on treatment and 27.7% had controlled fasting plasma glucose. The awareness, treatment and control of diabetes were substantially higher in the urban population and among women. CONCLUSIONS: The large differences in all diabetes indices between urban and rural regions, if confirmed in larger studies, may suggest an impact of westernised and urbanised lifestyle as well as access to health care.

Levels and distribution of self-rated health in the Kazakh population: results from the Kazakhstan household health survey 2012.

BACKGROUND: The high and fluctuating mortality and rising health inequalities in post-Soviet countries have attracted considerable attention. However, there are very few individual-level data on distribution of health outcomes in Central Asian countries of the former Soviet Union. We analysed socioeconomic predictors of two self-rated health outcomes in a national survey in Kazakhstan. METHODS: We used data from the 2012 Kazakhstan Household Health Survey on 12,560 respondents aged 15+. Self-rated health, self-reported worsening of health, and a range of socio-demographic variables were collected in an interview. The self-rated health outcomes were dichotomized and logistic regression was used to estimate their associations with education, income, ownership of a car, second house and computer, marital status, ethnicity and urban/rural residence. RESULTS: The prevalence of poor/very poor self-rated health was 5.3%, and 11.0% of participants reported worse health compared to 1 year ago. After controlling for age, sex and region, all socio-demographic factors were related to self-rated health. After adjusting for all variables, education and car ownership showed the most consistent effects; the odds ratio of poor health and worsening of health were 0.43 (95% confidence interval 0.32-0.58) and 0.54 (0.44-0.68) for university vs. primary education, respectively, and 0.64 (0.51-0.82) and 0.68 (0.58-0.80) for car ownership, respectively. Unmarried persons, ethnic Russians and urban residents also had increased prevalence of poor health in multivariable models. CONCLUSIONS: Despite the limitations of using subjective health measures, these data suggest strong associations between two measures of self-rated health and a number of socioeconomic characteristics. Future studies and health policy initiatives in Kazakhstan and other Central Asian countries should take social determinants of health into account.

Complete Genome Sequence of the Probiotic Lactic Acid Bacterium Lactobacillus Rhamnosus.

INTRODUCTION: Lactobacilli are a bacteria commonly found in the gastrointestinal tract. Some species of this genus have probiotic properties. The most common of these is Lactobacillus rhamnosus, a microoganism, generally regarded as safe (GRAS). It is also a homofermentative L-(+)-lactic acid producer. The genus Lactobacillus is characterized by an extraordinary degree of the phenotypic and genotypic diversity. However, the studies of the genus were conducted mostly with the unequally distributed, non-random choice of species for sequencing; thus, there is only one representative genome from the Lactobacillus rhamnosus clade available to date. The aim of this study was to characterize the genome sequencing of selected strains of Lactobacilli. METHODS: 109 samples were isolated from national domestic dairy products in the laboratory of Center for life sciences. After screaning isolates for probiotic properties, a highly active Lactobacillus spp strain was chosen.Genomic DNA was extracted according to the manufacturing protocol (Wizard® Genomic DNA Purification Kit). The Lactobacillus rhamnosus strain was identified as the highly active Lactobacillus strain accoridng to its morphological, cultural, physiological, and biochemical properties, and a genotypic analysis. RESULTS: The genome of Lactobacillus rhamnosus was sequenced using the Roche 454 GS FLX (454 GS FLX) platforms. The initial draft assembly was prepared from 14 large contigs (20 all contigs) by the Newbler gsAssembler 2.3 (454 Life Sciences, Branford, CT). CONCLUSION: A full genome-sequencing of selected strains of lactic acid bacteria was made during the study.

Health benefits of new symbiotic "NAR".

INTRODUCTION: The immune-modulatory effects of synbiotics and their ability to reduce free radical levels may be useful for functional food that is able to be active throughout whole period of colonization of the gastrointestinal tract.The aim of the present study was to investigate the immune-modulatory and antioxidant effects of the synbiotic product "NАR," a probiotic beverage. METHODS: The presence of IL-2, IL-4, IL-6, IL-8, IL-10, αTNF, γIFN, Ig A, Ig M, and Ig E was studied in vitro using a solid immunosorbent analysis. The total antioxidant activities of superoxide dismutase and glutathione reductase were determined by a spectrophotometry using the Sigma-Aldrich sets. RESULTS: Studies of the immune-modulatory properties of the synbiotic product NAR showed 1.7 fold increase of γINF levels (p<0.01) in blood after consumption of the synbiotic product "NAR" in comparison to control values, whereas the concentrations of IL-4 and Ig E decreased 2.0 times (treatment: 9.3; control: 18.7; p<0.01) and 1.3 times (p<0.1), respectively. The consumption of the synbiotic product "NAR" caused an increase in the proportion of γINF/IL 4 (treatment: 15.4; control: 4.4; p<0.01), which indicates a reduction in functional activity of Th2-type lymphocytes in comparison with the function of Th1 cells.Our study showed a high level of the total antioxidant activity of the synbiotic product (67.4 mmol/ml). The antioxidant activity of the intact cells of consortium (15.3 mM/ml), which was the basis for the preparation of the symbiotic product, is several times lower than the activity observed in the symbiotic samples.Expression of SOD is one of the mechanisms of antioxidant stress radicals inactivation by bacteria. The analysis identified a superoxide dismutase activity of synbiotic product (1.42 U/mg protein). A glutathione reductase activity of the synbiotic product was elevated (0.06 U/ml). CONCLUSION: The majority of the inflammatory mediators found in the blood after the consumption of symbiotic product NAR were inflammatory mediators that activate a cellular component of the resistance. Moreover, the symbiotic product has a high antioxidant activity.

Genotype frequencies of polymorphic MDR1 variants in the Kazakhstani population.

INTRODUCTION: Statins appear to be handled by an ATP-dependent membrane transporter and three SNPs (C1236T (rs1128503), G2677T (rs2032582), and C3435T (rs1045642), which capture the common genetic variation at this locus. Individuals, who carry the T allele at each SNP (i.e., the T-T-T haplotype), have higher systemic exposure to simvastatin.A triallelic thymine (T) - guanine (G) - adenine (A), which is a point mutation at nucleotide 2677 in exon 22, leads to ABCB1 in a non-synonymous codons (GCT alanine, TCT serine, threonine ACT) at position 893 in a cytoplasmic loop of ATP-dependent membrane transporters. METHODS: Blood samples from healthy individuals were collected in the Republican Diagnostic Center, Astana, Kazakhstan. The research samples included 461 healthy people. Genomic DNA was extracted from peripheral blood using the 'salting out' procedure. For the MDR1 exon 21, 2677G>T/A (Ala893Ser/Thr) polymorphism was genotyped by PCR sequencing by the use of dye-terminator (ABI 3730xl sequencer). RESULTS: The GG allele appeared in 23% of samples, the GA in 6.7%, the GT in 44%, the non-G heterozygote in 4.5%, and the non-G homozygote in 18%. These results are consistent with previously published data. Importantly, the frequency of 2677T alleles in our group was 15.4%. This represents the lowest frequency of this allele compared to published data in different populations. The frequency of the 2677T allele in Asians and Caucasians varies from 38 to 62%, and is 15% for African Americans. On the other hand, the 2677A allele frequency in the Japanese varies from 15 to 22%, and in Caucasians from 2% and 4%. The 2677A allele frequency has been found in 4.6% of samples. CONCLUSIONS: Our study further emphasizes differences between various Asian populations and the importance of repeating this genetic study in different ethnic groups.