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1.
Blood Press ; : 1-7, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399019

RESUMO

PURPOSE: Elevated blood pressure (BP) in childhood has been associated with increased adulthood BP. However, BP and its change from childhood to adulthood and the risk of exaggerated adulthood exercise BP response are largely unknown. Therefore, we studied the association of childhood and adulthood BP with adulthood exercise BP response. MATERIALS AND METHODS: This investigation consisted of 406 individuals participating in the ongoing Cardiovascular Risk in Young Finns Study (baseline in 1980, at age of 6-18 years; follow-up in adulthood in 27-29 years since baseline). In childhood BP was classified as elevated according to the tables from the International Child Blood Pressure References Establishment Consortium, while in adulthood BP was considered elevated if systolic BP was ≥120 mmHg or diastolic BP was ≥80 mmHg or if use of antihypertensive medications was self-reported. A maximal cardiopulmonary exercise test with BP measurements was performed by participants in 2008-2009, and exercise BP was considered exaggerated (EEBP) if peak systolic blood pressure exceeded 210 mmHg in men and 190 mmHg in women. RESULTS: Participants with consistently high BP from childhood to adulthood and individuals with normal childhood but high adulthood BP had an increased risk of EEBP response in adulthood (relative risk [95% confidence interval], 3.32 [2.05-5.40] and 3.03 [1.77-5.17], respectively) in comparison with individuals with normal BP both in childhood and adulthood. Interestingly, individuals with elevated BP in childhood but not in adulthood also had an increased risk of EEBP [relative risk [95% confidence interval], 2.17 [1.35-3.50]). CONCLUSIONS: These findings reinforce the importance of achieving and sustaining normal blood pressure from childhood through adulthood.

2.
Sci Rep ; 11(1): 611, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436758

RESUMO

High blood pressure (BP) is a major risk factor for many noncommunicable diseases. The effect of mitochondrial DNA single-nucleotide polymorphisms (mtSNPs) on BP is less known than that of nuclear SNPs. We investigated the mitochondrial genetic determinants of systolic, diastolic, and mean arterial BP. MtSNPs were determined from peripheral blood by sequencing or with genome-wide association study SNP arrays in two independent Finnish cohorts, the Young Finns Study and the Finnish Cardiovascular Study, respectively. In total, over 4200 individuals were included. The effects of individual common mtSNPs, with an additional focus on sex-specificity, and aggregates of rare mtSNPs grouped by mitochondrial genes were evaluated by meta-analysis of linear regression and a sequence kernel association test, respectively. We accounted for the predicted pathogenicity of the rare variants within protein-encoding and the tRNA regions. In the meta-analysis of 87 common mtSNPs, we did not observe significant associations with any of the BP traits. Sex-specific and rare-variant analyses did not pinpoint any significant associations either. Our results are in agreement with several previous studies suggesting that mtDNA variation does not have a significant role in the regulation of BP. Future studies might need to reconsider the mechanisms thought to link mtDNA with hypertension.

3.
Ann Med ; 53(1): 160-168, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33238748

RESUMO

BACKGROUND: Increased left ventricular mass (LVM) predicts cardiovascular events and mortality. The objective of this study was to determine whether early-life exposures to body mass index (BMI) and systolic blood pressure (SPB) affects the left ventricular structure in adulthood. METHODS: We used longitudinal data from a 31-year follow-up to examine the associations between early-life (between ages 6-18) BMI and SPB on LVM in an adult population (N = 1864, aged 34-49). The burden of early-life BMI and SBP was defined as area under the curve. RESULTS: After accounting for contemporary adult determinants of LVM, early-life BMI burden associated significantly with LVM (3.61 g/SD increase in early-life BMI; [1.94 - 5.28], p < 0.001). Overweight in early-life (age- and sex-specific BMI values corresponding to adult BMI > 25 kg/m2) associated with 4.7% (2.5-6.9%, p < 0.0001) higher LVM regardless of BMI status in adulthood. Overweight in early-life combined with obesity in adulthood (BMI > 30kg/m2) resulted in a 21% (17.3-32.9%, p < 0.0001) increase in LVM. Higher early-life BMI was associated with a risk of developing eccentric hypertrophy. The burden of early-life SPB was not associated with adult LVM or left ventricular remodeling. CONCLUSIONS: High BMI in early-life confers a sustained effect on LVM and the risk for eccentric hypertrophy independently of adulthood risk factors. KEY MESSAGES Excess in BMI in early-life has an independent effect on LVM and the risk of developing eccentric hypertrophy regardless of overweight status in adulthood. Systolic blood pressure levels in early-life did not have an independent effect on LVM or LV remodeling. The clinical implication of this study is that primary prevention of obesity in early-life may prevent the development of high LVM and eccentric hypertrophy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33340230

RESUMO

BACKGROUND AND AIMS: Our objective was to study relationships between the new biomarker of vascular health, carotid artery longitudinal wall motion (CALM) and metabolic syndrome (MetS). METHODS: Carotid ultrasound and assessment of MetS and its components were performed with 281 subjects aged 30-45 years. In the longitudinal motion analysis, the amplitude of motion and the antegrade-oriented and retrograde-oriented components of motion between the intima-media complex and adventitial layer of the common carotid artery wall were assessed. RESULTS: Metabolic syndrome, according to the harmonized criteria, was detected in 53 subjects (19%). MetS was significantly associated with increased antegrade and decreased retrograde longitudinal motion in the carotid artery wall. Augmented antegrade amplitude of longitudinal motion was associated with obesity (ß = 0.149, p < .05) and low HDL cholesterol (ß = 0.177, p < .01). Attenuated retrograde amplitude of longitudinal motion was associated with hypertension (ß = -0.156, p < .05), obesity (ß = -0.138, p < .05) and hyperinsulinaemia (ß = -0.158, p < .01). Moreover, insulin resistance (homeostasis model assessment index above 2.44) was associated with adverse changes in CALM. CONCLUSION: Metabolic syndrome and insulin resistance were associated with alterations in CALM. In particular, hypertension, obesity and hyperinsulinaemia were associated with reduced total peak-to-peak amplitude as well as increased antegrade and reduced retrograde amplitudes, all of which might be markers of unfavourable vascular health.

5.
Ann Med ; : 1-25, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33305629

RESUMO

OBJECTIVE: To evaluate the association between childhood parental smoking exposure and the risk of overweight/obesity from childhood to adulthood. METHODS: This study leverages the data from two longitudinal population based cohort studies, the Cardiovascular Risk in Young Finns Study between years 1980-2011/2012 (YFS; N = 2,303;baseline age 3-18 years) and the Special Turku Coronary Risk Factor Intervention Project between years 1989-2009/2010 (STRIP; N = 632;baseline age 7 months). Weight, height and waist circumference were measured from childhood to adulthood. Overweight/obesity was defined as body mass index ≥25 kg/m2 in adults and using the Cole criteria in children. Central obesity was defined as waist circumference >100/90cm in men/women and as a waist-to-height ratio >0.50 in children. Statistical analyses were adjusted for age, sex, socioeconomic status, smoking, birth weight, parental ages, diet and physical activity. RESULTS: Childhood parental smoking exposure was associated with increased risk for life-course overweight/obesity (YFS: RR1.13, 95%CI 1.02-1.24; STRIP: RR1.57, 95%CI 1.10-2.26) and central obesity (YFS: RR1.18, 95%CI 1.01-1.38; STRIP: RR1.45, 95%CI 0.98-2.15). CONCLUSIONS: Childhood exposure to parental smoking is associated with increased risk of overweight/obesity over the life-course. Key messages Exposure to parental smoking in childhood was associated with increased risk of overweight/obesity, central obesity and adiposity measured by skinfold thickness from childhood to adulthood.

6.
Endocr Connect ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33289696

RESUMO

Parathyroid hormone has been related with the risk of hypertension, but the matter remains controversial. We examined the association of parathyroid hormone with central blood pressure and its determinants in 622 normotensive or never-treated hypertensive subjects aged 19-72 years without diabetes, cardiovascular or renal disease, or cardiovascular medications. The methods were whole-body impedance cardiography and analyses of pulse wave and heart rate variability. Cardiovascular function was examined in sex-specific tertiles of plasma parathyroid hormone (mean concentrations 3.0, 4.3 and 6.5 pmol/l, respectively) during head-up tilt. Explanatory factors for haemodynamics were further investigated using linear regression analyses. Mean age was 45.0 (SD 11.7) years, body mass index 26.8 (4.4) kg/m2, seated office blood pressure 141/90 (21/12) mmHg, and 309 subjects (49.7%) were male. Only five participants had elevated plasma parathyroid hormone and calcium concentrations. Highest tertile of parathyroid hormone presented with higher supine and upright aortic diastolic blood pressure (p<0.01) and augmentation index (p<0.01), and higher upright systemic vascular resistance (p<0.05) than the lowest tertile. The tertiles did not present with differences in pulse wave velocity, cardiac output, or measures of heart rate variability. In linear regression analyses, parathyroid hormone was an independent explanatory factor for aortic systolic (p=0.005) and diastolic (p=0.002) blood pressure, augmentation index (p=0.002), and systemic vascular resistance (p=0.031). To conclude, parathyroid hormone was directly related to central blood pressure, wave reflection, and systemic vascular resistance in subjects without cardiovascular comorbidities and medications. Thus, parathyroid hormone may play a role in the pathophysiology of primary hypertension.

7.
Eur Heart J ; 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33351885

RESUMO

AIMS : Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) inhibit lipoprotein lipase (LPL) and represent emerging drug targets to lower circulating triglycerides and reduce cardiovascular risk. To investigate the molecular effects of genetic mimicry of ANGPTL3 and ANGPTL4 inhibition and compare them to the effects of genetic mimicry of LPL enhancement. METHODS AND RESULTS : Associations of genetic variants in ANGPTL3 (rs11207977-T), ANGPTL4 (rs116843064-A), and LPL (rs115849089-A) with an extensive serum lipid and metabolite profile (208 measures) were characterized in six cohorts of up to 61 240 participants. Genetic associations with anthropometric measures, glucose-insulin metabolism, blood pressure, markers of kidney function, and cardiometabolic endpoints via genome-wide summary data were also explored. ANGPTL4 rs116843064-A and LPL rs115849089-A displayed a strikingly similar pattern of associations across the lipoprotein and lipid measures. However, the corresponding associations with ANGPTL3 rs11207977-T differed, including those for low-density lipoprotein and high-density lipoprotein particle concentrations and compositions. All three genotypes associated with lower concentrations of an inflammatory biomarker glycoprotein acetyls and genetic mimicry of ANGPTL3 inhibition and LPL enhancement were also associated with lower C-reactive protein. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower waist-to-hip ratio, improved insulin-glucose metabolism, and lower risk of coronary heart disease and type 2 diabetes, whilst genetic mimicry of ANGPTL3 was associated with improved kidney function. CONCLUSIONS : Genetic mimicry of ANGPTL4 inhibition and LPL enhancement have very similar systemic metabolic effects, whereas genetic mimicry of ANGPTL3 inhibition showed differing metabolic effects, suggesting potential involvement of pathways independent of LPL. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower risk of coronary heart disease and type 2 diabetes. These findings reinforce evidence that enhancing LPL activity (either directly or via upstream effects) through pharmacological approaches is likely to yield benefits to human health.

8.
Int J Epidemiol ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33221853

RESUMO

BACKGROUND: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. METHODS: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies. RESULTS: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids. CONCLUSIONS: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities.

9.
Sci Rep ; 10(1): 19223, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154477

RESUMO

The atherogenic process begins already in childhood and progresses to symptomatic condition with age. We investigated the association of cholesterol efflux capacity (CEC) and vascular markers of subclinical atherosclerosis in healthy, young adults. CEC was determined in 2282 participants of the Young Finns study using cAMP treated 3H-cholesterol-labeled J774 cells. The CEC was correlated to baseline and 6-year follow-up data of cardiovascular risk factors and ultrasound measurements of arterial structure and function. CEC was higher in women, correlated with total cholesterol, HDL-C, and apolipoprotein A-I, but not with LDL-C or apolipoprotein B. Compared to the lowest CEC quartile, the highest CEC quartile was significantly associated with high CRP levels and inversely associated with adiponectin. At baseline, high CEC was associated with decreased flow-mediated dilation (FMD) and carotid artery distensibility, as well as an increased Young's modulus of elasticity, indicating adverse changes in arterial structure, and function. The association reversed with follow-up FMD data, indicating the interaction of preclinical parameters over time. A higher CEC was directly associated with a lower risk of subclinical atherosclerosis at follow-up. In young and healthy subjects, CEC was associated with important lipid risk parameters at baseline, as in older patients and CAD patients, but inversely with early risk markers for subclinical atherosclerosis.

10.
Int J Cardiol Heart Vasc ; 31: 100639, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33015317

RESUMO

Background: Intraventricular conduction delays (IVCDs) are hallmarks of heart failure (HF) and structural heart disease (SHD) but their prognostic value for HF and SHD is unclear. Methods: Relation of eight IVCDs and the incidence of first-time HF or SHD was studied in a nationally representative random sample of 6080 Finnish subjects aged ≥ 30 years (mean age 52.1, SD 14.5 years) who participated in the health examination including 12-lead ECG. Results: During 16.5 years' follow up, half of the subjects with left bundle branch block (LBBB) and one third of the subjects with non-specific IVCD developed HF. After controlling for known clinical risk factors the hazard ratio (HR) for new-onset HF for LBBB was 3.29 (95% confidence interval 1.93-5.63, P < 0.001) and 3.53 for non-specific IVCD (1.65-7.55, P = 0.001). In corresponding analysis, LBBB predicted SHD with HR 2.60 (1.21-5.62, P = 0.015). Excluding subjects with history of heart disease, including coronary heart disease, did not have impact on results. Right bundle branch block and other IVCDs displayed no relation to endpoints. Conclusion: LBBB and non-specific IVCD were associated with more than three-fold risk of new-onset HF. Furthermore, LBBB was associated with novel SHD. Their presence should alert clinician even in subjects free from any known heart disease.

11.
Anatol J Cardiol ; 24(5): 326-333, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33122478

RESUMO

OBJECTIVE: TCF7L2 is a repressor and transactivator of genes, and its variants are strongly associated with diabetes. This study aimed to evaluate the sex-specific relationship between the most common TCF7L2 gene variants (-98368G>T, rs12255372 and -47833C>T, rs7903146) with diabetes and coronary heart disease in Turkish Adult Risk Factor (TARF) Study. METHODS: Single nucleotide variants (SNVs) have been genotyped using the TaqMan allelic discrimination assays in 2,024 (51.3% in women, age: 55±11.8) Turkish adults participating in the TARF study. Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements. RESULTS: Among the TARF study participants, 11.7%, 24.3%, 14.1%, and 38.3% had diabetes, hypertension, coronary heart disease (CHD), and obesity, respectively. The frequencies of T allele for -47833C>T and -98368G>T in Turkish adults were determined to be 0.35 and 0.33, respectively. -47833C>T was significantly associated with higher fasting glucose concentrations in all participants, especially in men. Both SNVs were significantly associated with diabetes and CHD in all participants (p<0.05). When study population was stratified according to sex, -98368G>T was associated with diabetes in women (p=0.041) and -47833C>T was associated with diabetes and CHD in men (p=0.018 and p=0.032, respectively). Also, both SNVs and the diplotypes of common haplotype (H1) remained strongly associated with type 2 diabetes after risk factors were adjusted (p<0.05). CONCLUSION: T allele homozygosity of two SNVs as well as the diplotype H1-/H1- reflects risk of diabetes primarily in men. Enhanced CHD risk is determined by the presence of diplotype H1-/H1- among nondiabetic participants.

12.
Free Radic Biol Med ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33098999

RESUMO

OBJECTIVE: Oxidation of low-density lipoprotein (LDL) may promote atherosclerosis, whereas the reverse transport of oxidized lipids by high-density lipoprotein (HDL) may contribute to atheroprotection. To provide insights into the associations of lipoprotein lipid oxidation markers with lipoprotein subclasses at the population level, we investigated the associations of oxidized HDL lipids (oxHDLlipids) and oxidized LDL lipids (oxLDLlipids) with lipoprotein subclasses in a population-based cross-sectional study of 1395 Finnish adults ages 24-39 years. METHODS: The analysis of oxidized lipids was based on the determination of the baseline level of conjugated dienes in lipoprotein lipids. A high-throughput nuclear magnetic resonance (NMR) platform was used to quantify circulating lipoprotein subclass concentrations and analyze their lipid compositions. RESULTS: OxHDLlipids were mainly not associated with lipoprotein subclass lipid concentrations and lipid composition after adjustment for Apolipoprotein-A1 (Apo-A1), waist circumference and age. OxLDLlipids were associated with several markers of lipoprotein subclass lipid concentrations and composition after adjustment for Apolipoprotein-B (Apo-B), age and waist circumference. Several measures of HDL and LDL subclasses, including phospholipid and triglyceride composition, associated directly with oxLDLlipids. Cholesterol ester and free cholesterol composition in HDL and LDL associated inversely with oxLDLlipids. CONCLUSION: We conclude that these results do not support the idea that HDL's particle size or composition would reflect its functional capacity in the reverse transport of oxidized lipids. On the contrary, oxLDLlipids were associated with the entire lipoprotein subclass profile, including numerous associations with the compositional descriptors of the particles. This is in line with the suggested role of LDL oxidation in atherogenesis.

13.
Ann Noninvasive Electrocardiol ; : e12799, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32975832

RESUMO

BACKGROUND: Inverted T waves in the electrocardiogram (ECG) have been associated with coronary heart disease (CHD) and mortality. The pathophysiology and prognostic significance of T-wave inversion may differ between different anatomical lead groups, but scientific data related to this issue is scarce. METHODS: A representative sample of Finnish subjects (n = 6,354) aged over 30 years underwent a health examination including a 12-lead ECG in the Health 2000 survey. ECGs with T-wave inversions were divided into three anatomical lead groups (anterior, lateral, and inferior) and were compared to ECGs with no pathological T-wave inversions in multivariable-adjusted Fine-Gray and Cox regression hazard models using CHD and mortality as endpoints. RESULTS: The follow-up for both CHD and mortality lasted approximately fifteen years (median value with interquartile ranges between 14.9 and 15.3). In multivariate-adjusted models, anterior and lateral (but not inferior) T-wave inversions associated with increased risk of CHD (HR: 2.37 [95% confidence interval 1.20-4.68] and 1.65 [1.27-2.15], respectively). In multivariable analyses, only lateral T-wave inversions associated with increased risk of mortality in the entire study population (HR 1.51 [1.26-1.81]) as well as among individuals with no CHD at baseline (HR 1.59 [1.29-1.96]). CONCLUSIONS: The prognostic information of inverted T waves differs between anatomical lead groups. T-wave inversion in the anterior and lateral lead groups is independently associated with the risk of CHD, and lateral T-wave inversion is also associated with increased risk of mortality. Inverted T wave in the inferior lead group proved to be a benign phenomenon.

14.
Clin Nutr ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32994068

RESUMO

BACKGROUND & AIMS: The influence of dietary calcium intake in childhood on adult cardiovascular health is unknown, particularly in those with long-term high intake. To examine both linear and non-linear associations of childhood and long-term (between childhood and adulthood) dietary calcium intake with adult cardiovascular risk outcomes. METHODS: A population-based prospective cohort study in Finland (n = 1029, aged 3-18 years at baseline). Dietary calcium intake was assessed in childhood (1980, baseline) and adulthood (mean of available data from 2001, 2007 and 2011). Long-term dietary calcium intake was calculated as the mean between childhood and adulthood. Outcomes were measured in 2001, 2007, and/or 2011, and the latest available data were used for analyses, including high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity (PWV), carotid artery compliance (CAC), Young's elastic modulus (YEM), and stiffness index (SI). RESULTS: There were no significant non-linear or linear associations between childhood or long-term dietary calcium intake with any adult cardiovascular outcomes, after adjustment for age, sex, and childhood and adulthood confounders (e.g., body mass index, systolic blood pressure, smoking, physical activity, fruit and vegetable consumption). CONCLUSIONS: Childhood or long-term dietary calcium intake that is higher than the recommended level is not associated with increased cardiovascular risk in adulthood.

15.
Ann Noninvasive Electrocardiol ; : e12788, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32804416

RESUMO

BACKGROUND: Previous population studies have presented conflicting results regarding the prognostic impact of intraventricular conduction delays (IVCD). METHODS: We studied long-term prognostic impact and the association with comorbidities of eight IVCDs in a random sample of 6,299 Finnish subjects (2,857 men and 3,442 women, mean age 52.8, SD 14.9 years) aged 30 or over who participated in the health examination including 12-lead ECG. For left bundle branch block (LBBB) and non-specific IVCD (NSIVCD), two different definitions were used. RESULTS: During 16.5 years' follow-up, 1,309 of the 6,299 subjects (20.8%) died and of these 655 (10.4%) were cardiovascular (CV) deaths. After controlling for known clinical risk factors, the hazard ratio for CV death, compared with individuals without IVCD, was 1.55 for the Minnesota definition of LBBB (95% confidence interval 1.04-2.31, p = .032) and 1.27 (95% confidence interval 0.80-2.02, p = .308) for the Strauss' definition of LBBB. Subjects with NSIVCD were associated with twofold to threefold increase in CV mortality depending on the definition. While right bundle branch block, left anterior fascicular block and incomplete bundle branch blocks were associated with seemingly higher mortality, this was no longer the case after adjustment for age and sex. The presence of R-R' pattern was not associated with any adverse outcome. CONCLUSIONS: In a population study with long-term follow-up, NSIVCD and Minnesota definition of LBBB were independently associated with CV mortality. Other IVCDs had no significant impact on prognosis. The prognostic impact of LBBB and NSIVCD was affected by the definition of the conduction disorder.

16.
J Am Heart Assoc ; 9(14): e015288, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32627629

RESUMO

Background Whether long-term exposure to overweight or obesity from early life to adulthood has a detrimental influence on health outcomes is unknown. We aimed to investigate whether duration of overweight or obesity from youth to adulthood is associated with adult cardiometabolic risk. Methods and Results A population-based cohort study was performed of 1268 youths, aged 3 to 18 years, with follow-ups at 3, 6, 9, 12, 21, 27, and 31 years. Duration of overweight or obesity over 31-year follow-up was calculated. Adulthood outcomes included type 2 diabetes mellitus, impaired fasting glucose, high insulin levels, high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity, carotid artery compliance, Young elastic modulus, and stiffness index. Rates of overweight/obesity were 7.9% at baseline and 55.9% after 31 years. After adjustment for confounders, longer duration of overweight or obesity was associated with increased risk of all outcomes (relative risk ranged from 1.45-9.06 for type 2 diabetes mellitus, impaired fasting glucose, carotid intima-media thickness, hypertension, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides; ß from 0.370-0.543 m/s for pulse wave velocity; -0.193 to -0.237 %/10 mm Hg for carotid artery compliance; 52.1-136.8 mm Hg·mm for Young elastic modulus; and 0.554-0.882 for stiffness index). When body mass index was further adjusted, these associations disappeared or were substantially reduced. Detrimental associations of adult body mass index with all outcomes were robust to adjustment for confounders and duration of overweight or obesity. Conclusions Overweight or obesity in adulthood rather than childhood appears to be more important for adult cardiometabolic health.

17.
Hypertension ; 76(1): 195-205, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32520614

RESUMO

We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with P<1×10-5. In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated (P<1×10-7) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with P<0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100% of the correlations of systolic BP with cg19693031 (TXNIP) and cg00716257 (JDP2) determined by environmental effects acting on both systolic BP and methylation levels.

18.
Biosci Rep ; 40(7)2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32583859

RESUMO

Smoking as a major risk factor for morbidity affects numerous regulatory systems of the human body including DNA methylation. Most of the previous studies with genome-wide methylation data are based on conventional association analysis and earliest threshold-based gene set analysis that lacks sensitivity to be able to reveal all the relevant effects of smoking. The aim of the present study was to investigate the impact of active smoking on DNA methylation at three biological levels: 5'-C-phosphate-G-3' (CpG) sites, genes and functionally related genes (gene sets). Gene set analysis was done with mGSZ, a modern threshold-free method previously developed by us that utilizes all the genes in the experiment and their differential methylation scores. Application of such method in DNA methylation study is novel. Epigenome-wide methylation levels were profiled from Young Finns Study (YFS) participants' whole blood from 2011 follow-up using Illumina Infinium HumanMethylation450 BeadChips. We identified three novel smoking related CpG sites and replicated 57 of the previously identified ones. We found that smoking is associated with hypomethylation in shore (genomic regions 0-2 kilobases from CpG island). We identified smoking related methylation changes in 13 gene sets with false discovery rate (FDR) ≤ 0.05, among which is olfactory receptor activity, the flagship novel finding of the present study. Overall, we extended the current knowledge by identifying: (i) three novel smoking related CpG sites, (ii) similar effects as aging on average methylation in shore, and (iii) a novel finding that olfactory receptor activity pathway responds to tobacco smoke and toxin exposure through epigenetic mechanisms.

19.
Blood Press ; 29(6): 362-369, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32597238

RESUMO

PURPOSE: To study whether systemic hemodynamics, especially systemic vascular resistance, predicts the development of hypertension and improves the risk prediction of incident hypertension beyond common risk factors in the risk models in young adults. MATERIALS AND METHODS: Typical risk factors for hypertension in the risk prediction models (systolic and diastolic blood pressure, parental history of hypertension, age, sex, body-mass index, smoking), laboratory values (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, C-reactive protein), heart rate (HR), stroke index (SI), and systemic vascular resistance index (SVRI) calculated by whole-body impedance cardiography were evaluated in 2007 and blood pressure in 2011 in 1293 Finnish adults (aged 30-45 years; females 56%; n = 1058 normotensive in 2007). RESULTS: Of hemodynamic variables, SVRI and HR evaluated in 2007 were independently associated with systolic blood pressure (p < 0.001 and p = 0.047, respectively) and SVRI with diastolic blood pressure measured in 2011 (p = 0.014), and SVRI and HR were independent predictors of incident hypertension (p < 0.001 and p = 0.024, respectively). SVRI was the most significant predictor of incident hypertension independently of other risk factors (odds ratio 2.73 per 1 standard deviation increase, 95% confidence interval 1.93-3.94, p < 0.001). The extended prediction model (including SVRI) improved the incident hypertension risk prediction beyond other risk factors, with an area under the receiver operating characteristic curve of 0.846 versus 0.817 (p = 0.042) and a continuous net reclassification improvement of 0.734 (p < 0.001). CONCLUSIONS: These findings suggest that systemic vascular resistance index predicts the incidence of hypertension in young adults and that the evaluation of systemic hemodynamics could provide an additional tool for hypertension risk prediction.

20.
Aging (Albany NY) ; 12(12): 12376-12392, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32575070

RESUMO

Telomeres are short segments in chromosome ends, the length of which is reduced during cell lifecycles. We examined the association of mean leukocyte telomere length (LTL) and short telomere proportion (STP) with hemodynamic variables in normotensive and never-treated hypertensive volunteers (n=566, 19-72 years). STP and mean LTL were determined using Southern blotting, and supine hemodynamics recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. The analyses were adjusted for age, body mass index (BMI), alcohol use, smoking, plasma chemistry, and estimated glomerular filtration rate (eGFR). In univariate analyses, mean LTL and STP both correlated with age, BMI, eGFR, aortic blood pressure, augmentation index, and pulse wave velocity (p<0.05 for all). Mean LTL also correlated with systemic vascular resistance (p<0.05). In linear regression analyses of all hemodynamic variables, mean LTL was only an independent explanatory factor for augmentation index (Beta -0.006, p=0.032), while STP was not an explanatory factor for any of the hemodynamic variables, in contrast to age, BMI and several cardiovascular risk factors. To conclude, augmentation index was predominantly related with chronological aging, but also with mean LTL, suggesting that this variable of central wave reflection is a modest marker of vascular biological aging.

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