SARS-CoV-2 Impact on Red Blood Cell Morphology.

Severe COVID-19 alters the biochemical and morphological characteristics of blood cells in a wide variety of ways. To date, however, the vast majority of research has been devoted to the study of leukocytes, while erythrocyte morphological changes have received significantly less attention. The aim of this research was to identify erythrocyte morphology abnormalities that occur in COVID-19, compare the number of different poikilocyte types, and measure erythrocyte sizes to provide data on size dispersion. Red blood cells obtained from 6 control donors (800-2200 cells per donor) and 5 COVID-19 patients (800-1900 cells per patient) were examined using low-voltage scanning electron microscopy. We did not discover any forms of erythrocyte morphology abnormalities that would be specific to COVID-19. Among COVID-19 patients, we observed an increase in the number of acanthocytes (p = 0.01) and a decrease in the number of spherocytes (p = 0.03). In addition, our research demonstrates that COVID-19 causes an increase in the median (p = 0.004) and interquartile range (p = 0.009) when assessing erythrocyte size. The limitation of our study is a small number of participants.

Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study.

AIM: To test the association of alcohol consumption with total and cause-specific mortality risk. DESIGN: Prospective observational multi-centre population-based study. SETTING: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. PARTICIPANTS: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). MEASUREMENTS: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. FINDINGS: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7-14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7-20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10-35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. CONCLUSIONS: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.

Longitudinal trajectories of blood lipid levels in an ageing population sample of Russian Western-Siberian urban population.

This study investigated 12-year blood lipid trajectories and whether these trajectories are modified by smoking and lipid lowering treatment in older Russians. To do so, we analysed data on 9,218 Russian West-Siberian Caucasians aged 45-69 years at baseline participating in the international HAPIEE cohort study. Mixed-effect multilevel models were used to estimate individual level lipid trajectories across the baseline and two follow-up examinations (16,445 separate measurements over 12 years). In all age groups, we observed a reduction in serum total cholesterol (TC), LDL-C and non-HDL-C over time even after adjusting for sex, statin treatment, hypertension, diabetes, social factors and mortality (P<0.01). In contrast, serum triglyceride (TG) values increased over time in younger age groups, reached a plateau and decreased in older age groups (> 60 years at baseline). In smokers, TC, LDL-C, non-HDL-C and TG decreased less markedly than in non-smokers, while HDL-C decreased more rapidly while the LDL-C/HDL-C ratio increased. In subjects treated with lipid-lowering drugs, TC, LDL-C and non-HDL-C decreased more markedly and HDL-C less markedly than in untreated subjects while TG and LDL-C/HDL-C remained stable or increased in treatment naïve subjects. We conclude, that in this ageing population we observed marked changes in blood lipids over a 12 year follow up, with decreasing trajectories of TC, LDL-C and non-HDL-C and mixed trajectories of TG. The findings suggest that monitoring of age-related trajectories in blood lipids may improve prediction of CVD risk beyond single measurements.

Heterogeneous Manifestations of Epithelial-Mesenchymal Plasticity of Circulating Tumor Cells in Breast Cancer Patients.

To date, there is indisputable evidence of significant CTC heterogeneity in carcinomas, in particular breast cancer. The heterogeneity of CTCs is manifested in the key characteristics of tumor cells related to metastatic progression - stemness and epithelial-mesenchymal (EMT) plasticity. It is still not clear what markers can characterize the phenomenon of EMT plasticity in the range from epithelial to mesenchymal phenotypes. In this article we examine the manifestations of EMT plasticity in the CTCs in breast cancer. The prospective study included 39 patients with invasive carcinoma of no special type. CTC phenotypes were determined by flow cytometry before any type of treatment. EMT features of CTC were assessed using antibodies against CD45, CD326 (EpCam), CD325 (N-cadherin), CK7, Snail, and Vimentin. Circulating tumor cells in breast cancer are characterized by pronounced heterogeneity of EMT manifestations. The results of the study indicate that the majority of heterogeneous CTC phenotypes (22 out of 24 detectable) exhibit epithelial-mesenchymal plasticity. The variability of EMT manifestations does not prevent intravasation. Co-expression of EpCAM and CK7, regardless of the variant of co-expression of Snail, N-cadherin, and Vimentin, are associated with a low number of CTCs. Intrapersonal heterogeneity is manifested by the detection of several CTC phenotypes in each patient. Interpersonal heterogeneity is manifested by various combinations of CTC phenotypes in patients (from 1 to 17 phenotypes).

Genomic insights into the formation of human populations in East Asia.

The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet-where it forms approximately 84% of the gene pool in some groups-and to the Central Plain, where it has contributed around 59-84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai-Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.

Quantifying the contribution of established risk factors to cardiovascular mortality differences between Russia and Norway.

Surprisingly few attempts have been made to quantify the simultaneous contribution of well-established risk factors to CVD mortality differences between countries. We aimed to develop and critically appraise an approach to doing so, applying it to the substantial CVD mortality gap between Russia and Norway using survey data in three cities and mortality risks from the Emerging Risk Factor Collaboration. We estimated the absolute and relative differences in CVD mortality at ages 40-69 years between countries attributable to the risk factors, under the counterfactual that the age- and sex-specific risk factor profile in Russia was as in Norway, and vice-versa. Under the counterfactual that Russia had the Norwegian risk factor profile, the absolute age-standardized CVD mortality gap would decline by 33.3% (95% CI 25.1-40.1) among men and 22.1% (10.4-31.3) among women. In relative terms, the mortality rate ratio (Russia/Norway) would decline from 9-10 to 7-8. Under the counterfactual that Norway had the Russian risk factor profile, the mortality gap reduced less. Well-established CVD risk factors account for a third of the male and around a quarter of the female CVD mortality gap between Russia and Norway. However, these estimates are based on widely held epidemiological assumptions that deserve further scrutiny.

Development and validation of two SCORE-based cardiovascular risk prediction models for Eastern Europe: a multicohort study.

AIMS: Cardiovascular disease (CVD) risk prediction models are used in Western European countries, but less so in Eastern European countries where rates of CVD can be two to four times higher. We recalibrated the SCORE prediction model for three Eastern European countries and evaluated the impact of adding seven behavioural and psychosocial risk factors to the model. METHODS AND RESULTS: We developed and validated models using data from the prospective HAPIEE cohort study with 14 598 participants from Russia, Poland, and the Czech Republic (derivation cohort, median follow-up 7.2 years, 338 fatal CVD cases) and Estonian Biobank data with 4632 participants (validation cohort, median follow-up 8.3 years, 91 fatal CVD cases). The first model (recalibrated SCORE) used the same risk factors as in the SCORE model. The second model (HAPIEE SCORE) added education, employment, marital status, depression, body mass index, physical inactivity, and antihypertensive use. Discrimination of the original SCORE model (C-statistic 0.78 in the derivation and 0.83 in the validation cohorts) was improved in recalibrated SCORE (0.82 and 0.85) and HAPIEE SCORE (0.84 and 0.87) models. After dichotomizing risk at the clinically meaningful threshold of 5%, and when comparing the final HAPIEE SCORE model against the original SCORE model, the net reclassification improvement was 0.07 [95% confidence interval (CI) 0.02-0.11] in the derivation cohort and 0.14 (95% CI 0.04-0.25) in the validation cohort. CONCLUSION: Our recalibrated SCORE may be more appropriate than the conventional SCORE for some Eastern European populations. The addition of seven quick, non-invasive, and cheap predictors further improved prediction accuracy.

Heterogeneity of the nucleic acid repertoire of plasma extracellular vesicles demonstrated using high-sensitivity fluorescence-activated sorting.

The aim of this study was to investigate cell source-dependent nucleic acids repertoire of diverse subpopulations of plasma extracellular vesicles (EVs). Blood plasma from nine healthy volunteers was used for the analysis. Samples of EVs were obtained by differential centrifugation of plasma. The application of high-sensitivity fluorescence-activated vesicles sorting (hs-FAVS) using fluorophore-conjugated anti-CD41-FITC (Fluorescein isothiocyanate) and anti-CD235a-PE antibodies allowed the isolation of three subpopulations of EVs, namely CD41+ CD235a-, CD41-CD235a+ and CD41-CD235a dim. The high purity (>97%) of the sorted subpopulations was verified by high-sensitivity flow cytometry. Presence of nanosized objects in sorted samples was confirmed by combination of low-voltage scanning electron microscopy and dynamic light scattering. The amount of material in sorted samples was enough to perform Quantitative polymerase chain reaction (qPCR)-based nucleic acid quantification. The most prominent differences in the nucleic acid repertoire were noted between CD41+ CD235- vs. CD41-CD235a+ vesicles: the former contained significantly (p = 0.004) higher amount of mitochondrial DNA, and platelet enriched miR-21-5p (4-fold), miR-223-3p (38-fold) and miR-199a-3p (187-fold), but lower amount of erythrocyte enriched miR-451a (90-fold). CD41-CD235a+ and CD41-CD235a dim vesicles differed in levels of miR-451a (p = 0.016) and miR-21-5p (p = 0.031). Nuclear DNA was below the limit of detection in all EV subpopulations. The hs-FCM-based determination of the number of sorted EVs allowed the calculation of per single-event miRNA concentrations. It was demonstrated that the most abundant marker in CD41+ CD235a- subpopulation was miR-223-3p, reaching 38.2 molecules per event. In the CD41-CD235+ subpopulation, the most abundant marker was miR-451a, reaching 24.7 molecules per event. Taken together, our findings indicate that erythrocyte- and platelet-derived EVs carry different repertoires of nucleic acids, which were similar to the composition of their cellular sources.

Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure.

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (≤60, 61-70, 71-80, and >80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (P<0.001) from 4.4 (95% CI, 4.0-4.7) to 86.3 (76.1-96.5) for all-cause mortality and from 4.1 (3.9-4.6) to 59.8 (51.0-68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (P≤0.0033) from 1.42 (1.19-1.69) to 1.09 (1.05-1.12) and from 1.70 (1.51-1.92) to 1.12 (1.07-1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension.

Fruit, vegetable intake and blood pressure trajectories in older age.

Diet rich in fruits and vegetables (F&V) is an established protective factor for hypertension, but the available evidence regarding the impact of F&V consumption on age-related blood pressure change is limited. We examined whether systolic (SBP) and diastolic (DBP) blood pressure trajectories are influenced by F&V intakes in an ageing Russian cohort. Dietary data was available for 8997 men and women in the Health, Alcohol and Psychosocial Factors in Eastern Europe prospective cohort study. Blood pressure measurements were taken at three time-points over 12 years of follow-up, during which time the mean age of the sample changed from 58 to 69 years. The relationships between F&V intake and SBP and DBP were assessed using mixed-effect multilevel models. In the multivariable adjusted models, fruit intake was inversely related to both systolic and diastolic blood pressure at baseline (mean SBP and DBP was 3.5 mmHg and 1.4 mm Hg lower in the highest compared to the lowest intake tertiles, respectively (both p values < 0.001)). However, it was not associated with blood pressure change over time (difference in annual SBP and DBP change was 0.11 mmHg (p value = 0.138) and 0.01 mmHg (p value = 0.894), respectively). We found no significant link between vegetable intake and blood pressure, neither cross-sectionally nor longitudinally. In addition to the association with diet, we observed increasing SBP and mostly steady DBP over age, with deceleration and downward turn after the ages of 55-59 years. On the whole, this analysis found no consistent association between F&V intake and trajectories of blood pressure in older age.

Evidence-based proposal for the number of ambulatory readings required for assessing blood pressure level in research settings: an analysis of the IDACO database.

BACKGROUND: Guidelines on the required number of ambulatory blood pressure (ABP) readings focus on individual patients. Clinical researchers often face the dilemma of applying recommendations and discarding potentially valuable information or accepting fewer readings. METHODS: Starting from ABP recordings with ≥30/≥10 awake/asleep readings in 4277 participants enrolled in eight population studies in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (IDACO), we randomly selected a certain number of readings (from 30 to 1 awake and 10 to 1 asleep readings) at a time over 1000 bootstraps at each step. We evaluated: (i) concordance of the ABP level; (ii) consistency of the cross-classification based on office blood pressure and ABP; and (iii) accuracy in predicting cardiovascular complications. For each criterion, we fitted a regression line joining data points relating outcome to the number of readings covering the ranges of 30-20/10-7 for awake/asleep readings. RESULTS: Reducing readings widened the SD of the systolic/diastolic differences between full (reference) and selected recordings from 1.7/1.2 (30 readings) to 14.3/10.3 mm Hg (single reading) during wakefulness, and from 1.9/1.4 to 10.3/7.7 mm Hg during sleep; lowered the κ statistic from 0.94 to 0.63, and decreased the hazard ratio associated with 10/5 mm Hg increments in systolic/diastolic ABP from 1.21/1.14 to 1.06/1.04 during wakefulness and from 1.26/1.17 to 1.14/1.08 during sleep. The first data points falling off these regression lines during wakefulness/sleep corresponded to 8/3 and 8/4 readings for criteria (i) and (iii) and to 5 awake readings for criterion (ii). CONCLUSIONS: 24-h ambulatory recordings with ≥8/≥4 awake/asleep readings yielded ABP levels similar to recordings including the guideline-recommended ≥20/≥7 readings. These criteria save valuable data in a research setting, but are not applicable to clinical practice.

Determinants of social inequalities in stroke incidence across Europe: a collaborative analysis of 126 635 individuals from 48 cohort studies.

BACKGROUND: Knowledge on the origins of the social gradient in stroke incidence in different populations is limited. This study aims to estimate the burden of educational class inequalities in stroke incidence and to assess the contribution of risk factors in determining these inequalities across Europe. MATERIALS AND METHODS: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) Study comprises 48 cohorts recruited mostly in the 1980s and 1990s in four European regions using standardised procedures for baseline risk factor assessment and fatal and non-fatal stroke ascertainment and adjudication during follow-up. Among the 126 635 middle-aged participants, initially free of cardiovascular diseases, generating 3788 first stroke events during a median follow-up of 10 years, we estimated differences in stroke rates and HRs for the least versus the most educated individuals. RESULTS: Compared with their most educated counterparts, the overall age-adjusted excess hazard for stroke was 1.54 (95% CI 1.25 to 1.91) and 1.41 (95% CI 1.16 to 1.71) in least educated men and women, respectively, with little heterogeneity across populations. Educational class inequalities accounted for 86-413 and 78-156 additional stroke events per 100 000 person-years in the least compared with most educated men and women, respectively. The additional events were equivalent to 47%-130% and 40%-89% of the average incidence rates. Inequalities in risk factors accounted for 45%-70% of the social gap in incidence in the Nordic countries, the UK and Lithuania-Kaunas (men), but for no more than 17% in Central and South Europe. The major contributors were cigarette smoking, alcohol intake and body mass index. CONCLUSIONS: Social inequalities in stroke incidence contribute substantially to the disease rates in Europe. Healthier lifestyles in the most disadvantaged individuals should have a prominent impact in reducing both inequalities and the stroke burden.

Impact of perceived control on all-cause and cardiovascular disease mortality in three urban populations of Central and Eastern Europe: the HAPIEE study.

BACKGROUND: Inverse associations between perceived control and cardiovascular disease (CVD) have been reported in studies from Western Europe and the USA. To assess this relationship across different populations, we investigated the association between perceived control and all-cause and CVD mortality in three population-based cohorts of Eastern European countries. METHODS: We analysed data from a prospective cohort study in random population samples in Krakow (Poland), Novosibirsk (Russia) and six Czech towns. Baseline survey included structured questionnaire and objective examination in a clinic. Perceived control was assessed using an 11-item scale developed by the MacArthur Foundation Programme on Successful Midlife. Information on vital status was obtained from death registers. Effect of perceived control on mortality was assessed using Cox proportional hazards models. RESULTS: A total of 2377 deaths (1003 from CVD) occurred among 27 249 participants over a median 7-year follow-up. In the Czech and Polish cohorts, perceived control was inversely associated with mortality; the adjusted HRs for the lowest versus highest control quintiles were 1.71 (1.34 to 2.19) in men and 1.63 (1.14 to 2.35) in women for all-cause mortality and 2.31 (1.48 to 3.59) and 5.50 (2.14 to 14.13) for CVD deaths. There was no association between perceived control and mortality in Russia; the adjusted HRs for all-cause mortality were 1.03 (0.79 to 1.34) in men and 1.29 (0.82 to 2.02) in women. CONCLUSIONS: Low perceived control was associated with increased risk of all-cause and CVD mortality in Czech and Polish cohorts but not in Russia. It is possible that this inconsistency may partly reflect a different sociocultural understanding of the concept of control in Russia.

Prevalence, Treatment, and Control Rates of Conventional and Ambulatory Hypertension Across 10 Populations in 3 Continents.

Hypertension is a major global health problem, but prevalence rates vary widely among regions. To determine prevalence, treatment, and control rates of hypertension, we measured conventional blood pressure (BP) and 24-hour ambulatory BP in 6546 subjects, aged 40 to 79 years, recruited from 10 community-dwelling cohorts on 3 continents. We determined how between-cohort differences in risk factors and socioeconomic factors influence hypertension rates. The overall prevalence was 49.3% (range between cohorts, 40.0%-86.8%) for conventional hypertension (conventional BP ≥140/90 mm Hg) and 48.7% (35.2%-66.5%) for ambulatory hypertension (ambulatory BP ≥130/80 mm Hg). Treatment and control rates for conventional hypertension were 48.0% (33.5%-74.1%) and 38.6% (10.1%-55.3%) respectively. The corresponding rates for ambulatory hypertension were 48.6% (30.5%-71.9%) and 45.6% (18.6%-64.2%). Among 1677 untreated subjects with conventional hypertension, 35.7% had white coat hypertension (23.5%-56.2%). Masked hypertension (conventional BP <140/90 mm Hg and ambulatory BP ≥130/80 mm Hg) occurred in 16.9% (8.8%-30.5%) of 3320 untreated subjects who were normotensive on conventional measurement. Exclusion of participants with diabetes mellitus, obesity, hypercholesterolemia, or history of cardiovascular complications resulted in a <9% reduction in the conventional and 24-hour ambulatory hypertension rates. Higher social and economic development, measured by the Human Development Index, was associated with lower rates of conventional and ambulatory hypertension. In conclusion, high rates of hypertension in all cohorts examined demonstrate the need for improvements in prevention, treatment, and control. Strategies for the management of hypertension should continue to not only focus on preventable and modifiable risk factors but also consider societal issues.

The Cardiovascular Risk of White-Coat Hypertension.

BACKGROUND: The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood. OBJECTIVES: Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects. METHODS: European Society Hypertension guidelines were used as a 5-stage risk score. Low risk was defined as 0 to 2 risk factors, and high risk was defined as ≥3 to 5 risk factors, diabetes, and/or history of prior CVD events. Age- and cohort-matching was done between 653 untreated subjects with WCH and 653 normotensive control subjects. RESULTS: In a stepwise linear regression model, systolic WCE increased by 3.8 mm Hg (95% confidence interval [CI]: 3.1 to 4.6 mm Hg) per 10-year increase in age, and was similar in low- and high-risk subjects with or without prior CVD events. Over a median 10.6-year follow-up, incidence of new CVD events was higher in 159 high-risk subjects with WCH compared with 159 cohort- and age-matched high-risk normotensive subjects (adjusted hazard ratio [HR]: 2.06; 95% CI: 1.10 to 3.84; p = 0.023). The HR was not significant for 494 participants with low-risk WCH and age-matched low-risk normotensive subjects. Subgroup analysis by age showed that an association between WCH and incident CVD events is limited to older (age ≥60 years) high-risk WCH subjects; the adjusted HR was 2.19 (95% CI: 1.09 to 4.37; p = 0.027) in the older high-risk group and 0.88 (95% CI: 0.51 to 1.53; p = 0.66) in the older low-risk group (p for interaction = 0.044). CONCLUSIONS: WCE size is related to aging, not to CVD risk. CVD risk in most persons with WCH is comparable to age- and risk-adjusted normotensive control subjects.

Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study.

OBJECTIVE: The enzyme xanthine oxidoreductase (XOR) generates uric acid in the terminal steps of the purine metabolism; meanwhile reactive oxygen species are formed. We hypothesized that uric acid production, as assessed indirectly from XOR variants, is associated with hypertension. METHODS: Among 2769 participants (48.3% men; mean age 40.7 years) randomly recruited from European populations, we genotyped 25 tagging XOR SNPs and measured blood pressure (BP) at baseline and follow-up (median 8.8 years). The relation between variants of the XOR gene with changes in pulse pressure and mean arterial pressure over time; and incidence of hypertension, were analyzed. RESULTS: Compared with nonminor allele carriers, pulse pressure increased approximately 2 mmHg more in minor allele carriers of rs11904439 (P = 0.01), whereas mean arterial pressure and DBP increased approximately 1 mmHg less in minor allele carriers of rs2043013 (P = 0.01). In 2050, participants normotensive at baseline, hazard ratios contrasting risk of hypertension in minor allele carriers vs. nonminor allele carriers were 1.31 (95% confidence interval 1.03-1.68; P = 0.02) and 1.69 (95% confidence interval 1.11-2.57; P = 0.01) for rs11904439 and rs148756340, respectively. With the false discovery rate set at 0.25, the aforementioned associations retained significance. The changes in SBP from baseline to follow-up and the serum levels of uric acid at baseline (n = 1949) were not associated with XOR. CONCLUSION: Pending confirmation, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in BP and in the risk of hypertension.

Antioxidant vitamin intake and mortality in three Central and Eastern European urban populations: the HAPIEE study.

PURPOSE: The aim of the study was to assess the relationships between individual-level dietary intakes of antioxidant vitamins C, E and beta-carotene with all-cause and cause-specific mortality in three Central and Eastern European (CEE) populations. METHODS: Data from the Health, Alcohol and Psychosocial factors in Eastern Europe cohort study were used. At the baseline survey, between 2002 and 2005, 28,945 men and women aged 45-69 years were examined in Novosibirsk (Russia), Krakow (Poland) and seven Czech towns. Deaths in the cohorts were identified through mortality registers. Cox regression was used to estimate the association between vitamin consumption and all-cause, cardiovascular (CVD) disease and cancer mortality. RESULTS: In multivariable-adjusted analyses, there were no clear inverse associations between antioxidant vitamin intakes and mortality, although in some groups, several hazard ratios (HRs) were significant. For example, in men, compared with the lowest quintile of vitamin C intake, all-cause mortality in the third and fourth quintiles was lower by 28 % (HR 0.72; 95 % CI 0.61-0.85) and by 20 % (HR 0.80; 95 % CI 0.68-0.95), respectively. CVD mortality was lower by 35 % (HR 0.65; 95 % CI 0.50-0.84) and by 23 % (HR 0.77; 95 % CI 0.59-0.99) in third and fourth quintile of vitamin C intake, respectively. In women, the third and fourth quintiles of dietary intake of vitamin E were associated with reduced risk of all-cause death by 33 % (HR 0.67; 95 % CI 0.53-0.84) and by 23 % (HR 0.77; 95 % CI 0.61-0.97), respectively. Consumption of vitamin C, vitamin E and beta-carotene was not related to CVD mortality in women and to cancer mortality in either gender. CONCLUSION: This large prospective cohort study in CEE populations with low prevalence of vitamin supplementation did not find a strong, dose-response evidence for protective effects of antioxidant vitamin intake.

Alcohol consumption and physical functioning among middle-aged and older adults in Central and Eastern Europe: results from the HAPIEE study.

BACKGROUND: light-to-moderate drinking is apparently associated with a decreased risk of physical limitations in middle-aged and older adults. OBJECTIVE: to investigate the association between alcohol consumption and physical limitations in Eastern European populations. STUDY DESIGN: a cross-sectional survey of 28,783 randomly selected residents (45-69 years) in Novosibirsk (Russia), Krakow (Poland) and seven towns of Czech Republic. METHODS: physical limitations were defined as <75% of optimal physical functioning using the Physical Functioning (PF-10) Subscale of the Short-Form-36 questionnaire. Alcohol consumption was assessed by a graduated frequency questionnaire, and problem drinking was defined as ≥2 positive responses on the CAGE questionnaire. In the Russian sample, past drinking was also assessed. RESULTS: the odds of physical limitations were highest among non-drinkers, decreased with increasing drinking frequency, annual consumption and average drinking quantity and were not associated with problem drinking. The adjusted odds ratio (OR) of physical limitations in non-drinkers versus regular moderate drinkers was 1.61 (95% confidence interval: 1.48-1.75). In the Russian sample with past drinking available, the adjusted OR in those who stopped drinking for health reasons versus continuing drinkers was 3.19 (2.58-3.95); ORs in lifetime abstainers, former drinkers for non-health reasons and reduced drinkers for health reasons were 1.27 (1.02-1.57), 1.48 (1.18-1.85) and 2.40 (2.05-2.81), respectively. CONCLUSION: this study found an inverse association between alcohol consumption and physical limitations. The high odds of physical limitations in non-drinkers can be largely explained by poor health of former drinkers. The apparently protective effect of heavier drinking was partly due to less healthy former heavy drinkers who moved to lower drinking categories.

Age-specific differences between conventional and ambulatory daytime blood pressure values.

Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.

Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population.

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.