HIF3A cord blood methylation and systolic blood pressure at 4 years - a population-based cohort study.
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ABSTRACT:
SUBMITTER: Mansell T
PROVIDER: S-EPMC7678916 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Adriatic islanders have a high prevalence of metabolic syndrome that is not fully explained by previous behavioral, dietary, and genetic studies. Some DNA methylation remains stable and may be established in early life, whereas others are dynamic and may vary over time in response to different conditions. The objective of the present study was to identify stable and dynamic DNA methylation loci associated with cardiometabolic traits among the populations from the island of Hvar, the largest island in the eastern Adriatic coast. An epigenome-wide association study (EWAS) was conducted using peripheral blood that was longitudinally collected at two time points, 10 years apart. DNA methylation was analyzed via Infinium MethylationEPIC BeadArray. Stable and dynamic loci were identified using linear mixed models. A total of 43,041 loci were classified as stable, while 45,769 loci were classified as dynamic. Associations between various cardiometabolic traits and stable and dynamic methylation loci were respectively assessed using linear mixed effects models adjusted for age, sex, and smoking status. After adjustment for false-discovery rate, 24 CpG loci were significantly associated with systolic blood pressure (Q < 0.1), of which 22 were stable loci and 2 were dynamic loci; while 12/22 (55%) of the systolic blood-pressure-associated stable loci resided in a gene promoter. Additionally, there was one stable locus associated with serum calcium and one with C-reactive protein. The results suggest that multiple genes involved in the determination of systolic blood pressure may be regulated via epigenetic programming established in early life.
2023-01-01 | GSE207927 | GEO
Project description:Carotid intima-media thickness (cIMT) is a noninvasive marker of cardiovascular risk. The cIMT may be increased in patients with harmonisation, but little is known regarding the functional form of the association between blood pressure (BP) and cIMT in hypertensive and nonhypertensive persons. We aimed to define the shape of the association between BP and cIMT. We studied cIMT and ambulatory BP monitoring data from a single-center, cross-sectional, population-based study involving 696 adult participants from the STANISLAS cohort, a familial longitudinal cohort from the Nancy region of France. Participants with a history of hypertension were more likely to have a cIMT >900 μm and had higher mean cIMT (both P<0.001). The risk of cIMT >900 μm increased linearly with higher 24-hour and daytime systolic BP in participants both with and without history of hypertension. The relationship between systolic BP and the risk of cIMT >900 μm was not dependent on hypertension status (all P for interaction >0.10). In multivariable analysis adjusted on cardiovascular risk factors, each 5-mm Hg increase in systolic BP was associated with an 8-μm increase in cIMT (β=8.249 [95% CI 2.490-14.008], P=0.005). In contrast, the association between diastolic BP and cIMT was weaker and not significant. Systolic BP is linearly and continuously associated with higher cIMT in both hypertensive and nonhypertensive persons, suggesting a detrimental effect of BP on the vascular tree prior to overt hypertension. Similarly, it suggests a detrimental effect of BP at the higher end of the normal range in treated hypertensive patients. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01391442.
| S-EPMC4937282 | biostudies-literature
Project description:BACKGROUND:Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ?80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death. METHODS:A population-based cohort study was conducted using electronic health records of 144?403 participants ?80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ?5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportional-hazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death. RESULTS:During follow-up, 51?808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm?Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm?Hg, 15.2 at SBP 110 to 119 mm?Hg, and 22.7 at SBP <110 mm?Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm?Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40-6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30-7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life. CONCLUSIONS:A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life.
| S-EPMC5472195 | biostudies-literature
Project description:ObjectivesTo investigate the optimal systolic blood pressure goal above which new antihypertensive medications should be added or doses of existing medications increased ("systolic intensification threshold") and to determine the relation between delays in medication intensification and follow-up and the risk of cardiovascular events or death.DesignRetrospective cohort study.SettingPrimary care practices in the United Kingdom, 1986-2010.Participants88 756 adults with hypertension from The Health Improvement Network nationwide primary care research database.Main outcome measuresRates of acute cardiovascular events or death from any cause for patients with different hypertension treatment strategies (defined by systolic intensification threshold, time to intensification, and time to follow-up over the course of a 10 year treatment strategy assessment period) after adjustment for age, sex, smoking status, socioeconomic deprivation, history of diabetes, cardiovascular disease or chronic kidney disease, Charlson comorbidity index, body mass index, medication possession ratio, and baseline blood pressure.ResultsDuring a median follow-up of 37.4 months after the treatment strategy assessment period, 9985 (11.3%) participants had an acute cardiovascular event or died. No difference in risk of the outcome was seen between systolic intensification thresholds of 130-150 mm Hg, whereas systolic intensification thresholds greater than 150 mm Hg were associated with progressively greater risk (hazard ratio 1.21, 95% confidence interval 1.13 to 1.30; P<0.001 for intensification threshold of 160 mm Hg). Outcome risk increased progressively from the lowest (0-1.4 months) to the highest fifth of time to medication intensification (hazard ratio 1.12, 1.05 to 1.20; P=0.009 for intensification between 1.4 and 4.7 months after detection of elevated blood pressure). The highest fifth of time to follow-up (>2.7 months) was also associated with increased outcome risk (hazard ratio 1.18, 1.11 to 1.25; P<0.001).ConclusionsSystolic intensification thresholds higher than 150 mm Hg, delays of greater than 1.4 months before medication intensification after systolic blood pressure elevation, and delays of greater than 2.7 months before blood pressure follow-up after antihypertensive medication intensification were associated with increased risk of an acute cardiovascular event or death. These findings support the importance of timely medical management and follow-up in the treatment of patients with hypertension.
| S-EPMC4353282 | biostudies-literature
Project description:Recent publications have stated that the blood pressure (BP) measurement technique used in SPRINT (Systolic Blood Pressure Intervention Trial) was unattended. However, the SPRINT protocol does not address the issue of attendance. A survey was conducted immediately after SPRINT closeout visits were completed to inquire whether BP measurements were usually attended or unattended by staff. There were 4082 participants at 38 sites that measured BP after leaving the participant alone the entire time (always alone), 2247 at 25 sites that had personnel in the room the entire time (never alone), 1746 at 19 sites that left the participant alone only during the rest period (alone for rest), and 570 at 6 sites that left the participant alone only during the BP readings (alone for BP measurement). Similar systolic and diastolic BPs within randomized groups were noted during follow-up at the majority of visits in all 4 measurement categories. In the always alone and never alone categories, the intensive group had a similarly reduced risk for the primary outcome compared with the standard group (hazard ratio, 0.62; 95% confidence interval, 0.51-0.76 and hazard ratio, 0.64; 95% confidence interval, 0.46-0.91, respectively; pairwise interaction P value, 0.88); risk was not significantly reduced for the intensive group in the smaller alone-for-rest and the alone-for-BP-measurement categories. Similar BP levels and cardiovascular disease risk reduction were observed in the intensive group in SPRINT participants whether the measurement technique used was primarily attended or unattended. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.
| S-EPMC5967644 | biostudies-literature
Project description:The present study used harmonized data from eight studies (N?=?28,891) to examine the association between socioeconomic status (SES) and resting systolic blood pressure (SBP). The study replicates and extends our prior work on this topic by examining potential moderation of this association by race and gender. We also examined the extent to which body mass index (BMI), waist circumference (WC), and smoking might explain the association between SES and SBP. Data were available from six race/gender groups: 9200 Black women; 2337 Black men; 7248 White women; 6519 White men; 2950 Hispanic women; and 637 Hispanic men. Multivariable regression models showed that greater annual household income was associated with lower SBP in all groups except Hispanic men. The magnitude and form of this negative association differed across groups, with White women showing the strongest linear negative association. Among Black men and Hispanic women, the association was curvilinear: relatively flat among lower income levels, but then negative among higher income ranges. Education also was independently, negatively related to SBP, though evidence was weaker for race and gender differences in the strength of the association. Higher BMI and WC were associated with higher SBP, and current smoking with lower SBP. Inclusion of these risk factors resulted in only a modest change in the magnitude of the SBP and SES relation, accounting on average about 0.4?mmHg of the effect of income and 0.2?mmHg of the effect of education-effects unlikely to be clinically significant. Further understanding of mechanisms underlying the association between SBP and SES may improve risk stratification in clinical settings and potentially inform interventions aimed at reductions in social disparities in health.
| S-EPMC6804683 | biostudies-literature
Project description:SubjectThis study aimed to establish a normal range for ankle systolic blood pressure (SBP).MethodsA total of 948 subjects who had normal brachial SBP (90-139 mmHg) at investigation were enrolled. Supine BP of four limbs was simultaneously measured using four automatic BP measurement devices. The ankle-arm difference (An-a) on SBP of both sides was calculated. Two methods were used for establishing normal range of ankle SBP: the 99% method was decided on the 99% reference range of actual ankle BP, and the An-a method was the sum of An-a and the low or up limits of normal arm SBP (90-139 mmHg).ResultsWhether in the right or left side, the ankle SBP was significantly higher than the arm SBP (right: 137.1 ± 16.9 vs 119.7 ± 11.4 mmHg, P<0.05). Based on the 99% method, the normal range of ankle SBP was 94~181 mmHg for the total population, 84~166 mmHg for the young (18-44 y), 107~176 mmHg for the middle-aged(45-59 y) and 113~179 mmHg for the elderly (≥ 60 y) group. As the An-a on SBP was 13 mmHg in the young group and 20 mmHg in both middle-aged and elderly groups, the normal range of ankle SBP on the An-a method was 103-153 mmHg for young and 110-160 mmHg for middle-elderly subjects.ConclusionA primary reference for normal ankle SBP was suggested as 100-165 mmHg in the young and 110-170 mmHg in the middle-elderly subjects.
| S-EPMC4459970 | biostudies-literature
Project description:OBJECTIVES:To evaluate the effect of intensive systolic blood pressure (SBP) control in older adults with hypertension, considering cognitive and physical function. DESIGN:Secondary analysis. SETTING:Systolic Blood Pressure Intervention Trial (SPRINT) PARTICIPANTS: Adults 80?years or older. INTERVENTION:Participants with hypertension but without diabetes (N = 1167) were randomized to an SBP target below 120?mm Hg (intensive treatment) vs a target below 140?mm Hg (standard treatment). MEASUREMENTS:We measured the incidence of cardiovascular disease (CVD), mortality, changes in renal function, mild cognitive impairment (MCI), probable dementia, and serious adverse events. Gait speed was assessed via a 4-m walk test, and the Montreal Cognitive Assessment (MoCA) was used to quantify baseline cognitive function. RESULTS:Intensive treatment led to significant reductions in cardiovascular events (hazard ratio [HR] = .66; 95% confidence interval [CI] = .49-.90), mortality (HR = .67; 95% CI = .48-.93), and MCI (HR = .70; 95% CI = .51-.96). There was a significant interaction (P?<?.001) whereby participants with higher baseline scores on the MoCA derived strong benefit from intensive treatment for a composite of CVD and mortality (HR = .40; 95% CI = .28-.57), with no appreciable benefit in participants with lower scores on the MoCA (HR = 1.33 = 95% CI = .87-2.03). There was no evidence of heterogeneity of treatment effects with respect to gait speed. Rates of acute kidney injury and declines of at least 30% in estimated glomerular filtration rate were increased in the intensive treatment group with no between-group differences in the rate of injurious falls. CONCLUSION:In adults aged 80?years or older, intensive SBP control lowers the risk of major cardiovascular events, MCI, and death, with increased risk of changes to kidney function. The cardiovascular and mortality benefits of intensive SBP control may not extend to older adults with lower baseline cognitive function. TRIAL REGISTRATION:Clinicaltrials.gov identifier: NCT01206062. J Am Geriatr Soc 68:496-504, 2020.
| S-EPMC7056569 | biostudies-literature
Project description:Background: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these increased disease risks. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies. Methods and Results: Using Illumina's 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 of which are associated with genes) displayed significant methylation differences between GDM and control samples. Three of four candidate genes, ATP5A1, PRKCH, and SLC17A4, from our methylation screen and one, HIF3A, from the literature were validated by bisulfite pyrosequencing. The GDM effect on FCB methylation was more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM. However, the effect remained significant after adjustment for the maternal BMI and gestational week in a multivariate regression model. Conclusions: Our study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis and prognosis of adverse prenatal exposures and assessing the success of interventions during pregnancy.
2017-03-29 | GSE88929 | GEO
Project description:Background Intensive systolic blood pressure treatment (<120 mm Hg) in SPRINT (Systolic Blood Pressure Intervention Trial) improved survival compared with standard treatment (<140 mm Hg) over a median follow-up of 3.3 years. We projected life expectancy after observed follow-up in SPRINT using SPRINT-eligible participants in the NHLBI-PCS (National Heart, Lung, and Blood Institute Pooled Cohorts Study). Methods and Results We used propensity scores to weight SPRINT-eligible NHLBI-PCS participants to resemble SPRINT participants. In SPRINT participants, we estimated in-trial survival (<4 years) using a time-based flexible parametric survival model. In SPRINT-eligible NHLBI-PCS participants, we estimated posttrial survival (≥4 years) using an age-based flexible parametric survival model and applied the formula to SPRINT participants to predict posttrial survival. We projected overall life expectancy for each SPRINT participant and compared it to parametric regression (eg, Gompertz) projections based on SPRINT data alone. We included 8584 SPRINT and 10 593 SPRINT-eligible NHLBI-PCS participants. After propensity weighting, mean (SD) age was 67.9 (9.4) and 68.2 (8.8) years, and 35.5% and 37.6% were women in SPRINT and NHLBI-PCS, respectively. Using the NHLBI-PCS-based method, projected mean life expectancy from randomization was 21.0 (7.4) years with intensive and 19.1 (7.2) years with standard treatment. Using the Gompertz regression, life expectancy was 11.2 (2.3) years with intensive and 10.5 (2.2) years with standard treatment. Conclusions Combining SPRINT and NHLBI-PCS observed data likely offers a more realistic estimate of life expectancy than parametrically extrapolating SPRINT data alone. These results offer insight into the potential long-term effectiveness of intensive SBP goals.
| S-EPMC8200698 | biostudies-literature