Search

Background: We investigated the temporal causal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) progression with the risk of dysglycemia, insulin resistance, and dyslipidemia.Methods: We included 3862, 17.7-year-old, participants from the Avon Longitudinal Study of Parents and Children, followed up for 7 years. cfPWV, cIMT, and fasting plasma samples were repeatedly measured. We computed homeostatic model assessment (HOMA) of insulin resistance and percent pancreatic beta-cell function. Data were analyzed using logistic regression, linear mixed-effect, and cross-lagged structural equation models.Results: A higher cfPWV at 17.7 years was associated with higher insulin at age 24.5 years (odds ratio, 1.25 [CI, 1.08-1.44]; P=0.003), which slightly attenuated after covariates adjustment. Higher cIMT at 17.7 years was associated with lower insulin (odds ratio, 0.06 [0.01-0.95]; P=0.046) at 24.5 years, after covariate adjustments. In mixed-effect models, the 7-year progression in cfPWV (predictor) was directly associated with the increase in triglyceride (outcome). cIMT progression was associated with the 7-year increase in LDL (low-density lipoprotein), triglyceride, and glucose. In cross-lagged models, higher cfPWV at 17.7 years was associated with higher insulin (β=0.06, SE, 0.12, P=0.014), HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 24.5 years. However, insulin, HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 17.7 years were not associated with cfPWV at 24.5 years. Higher cIMT at 17.7 years was associated with reduced insulin, HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 24.5 years, but not vice versa. Higher glucose at 17.7 years was associated with higher cfPWV and cIMT at 24.5 years only.Conclusions: Arterial stiffness in adolescence may be a causal risk factor for hyperinsulinemia and insulin resistance in young adulthood. [ABSTRACT FROM AUTHOR]

We examined the temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) with the risk of overweight/obesity and elevated blood pressure (BP)/hypertension. We studied 3862 adolescents aged 17.7 years from the Avon Longitudinal Study of Parents and Children, followed-up for 7 years. cfPWV and cIMT were measured by ultrasound. Total and trunk fat mass and lean mass were assessed by dual-energy X-ray absorptiometry. Body mass index and BP were measured. Data were analyzed using logistic regression, linear mixed-effect, and cross-lagged structural equation models, with covariate adjustments. Among 1719 male and 2143 female participants, higher cfPWV at 17.7 years was associated with the risk of elevated systolic BP/hypertension (odds ratio, 1.20 [1.02-1.41]; P=0.026), elevated diastolic BP/hypertension (1.77 [1.32-2.38]; P<0.0001), body mass index-overweight/obesity (1.19 [1.01-1.41]; P=0.041), and trunk fat mass overweight/obesity (1.24 [1.03-1.49]; P=0.023) at 24.5 years. Higher cIMT at 17.7 years had no associations with obesity and elevated BP at follow-up. cfPWV progression was directly associated with 7-year increase in systolic BP (effect estimate 16 mm Hg [9-24]; P<0.0001) and diastolic BP (28 mm Hg [23-34]; P<0.0001). cIMT progression was directly associated with the 7-year increase of all adiposity measures and diastolic BP. In the temporal analysis, baseline cfPWV was directly associated with follow-up systolic and diastolic BP, however, baseline BP was unassociated with follow-up cfPWV. cfPWV but not cIMT was bidirectionally associated with adiposity. Obesity and hypertension prevention from adolescence may require developing novel approaches to mitigate arterial stiffness. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine whether estimated cardiorespiratory fitness (CRF), fat mass (FM), lean mass (LM), and adiponectin bidirectionally associate with arterial function and structure and if CRF mediates the relationship between cardiometabolic health and arterial outcomes in 9- to 11-yr-old children drawn from the Avon Longitudinal Study of Parents and Children birth cohort, United Kingdom., Methods: Brachial artery flow-mediated dilation (FMD), distensibility coefficient (DC), and carotid-radial pulse wave velocity (PWV) were measured by ultrasonography; CRF was measured during the submaximal ergometer test; total FM, trunk FM, and LM were measured by dual-energy x-ray absorptiometry; plasma adiponectin was measured by enzyme assay; and cardiometabolic health was computed based on the International Diabetes Federation criteria for diagnosing metabolic syndrome. We tested bidirectionality by including CRF, FM, LM, and adiponectin as exposures and FMD, DC, and PWV as outcomes, alternatively., Results: Among 5566 participants (2816 (51%) girls; median age, 9.75 yr), CRF per body mass0.21 was directly related to DC (β (95% confidence interval) = 0.004 (<0.0001 to 0.008); P = 0.046), whereas CRF per LM0.54 was inversely associated with PWV (-0.034 (-0.063 to -0.003); 0.032) after adjusting for covariates. These associations remained in bidirectional analyses. Total FM, trunk FM, and LM were bidirectionally and positively associated with FMD and DC. Total FM and trunk FM but not LM had bidirectional and inverse associations with PWV. Adiponectin was not related to FMD, DC, or PWV. CRF partially mediated the associations of cardiometabolic health with FMD (1.5% mediation), DC (12.1% mediation), and PWV (3.5% mediation)., Conclusions: Associations of poor cardiometabolic health with adverse arterial structure and function in childhood may be mitigated by increasing CRF. Higher CRF was associated with better arterial structure whereas higher total FM and trunk FM were associated with better arterial function and structure. In the reverse analysis, healthy arterial structure and function were independently associated with increased total FM and trunk FM, suggesting an "arterial paradox.", (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Objective: The epidemiological evidence of the role of dietary saturated fatty acids (SFA) in the development of coronary heart disease (CHD) is inconsistent. We investigated the associations of dietary fatty acids with the risk of CHD and carotid atherosclerosis in men with high SFA intake and high rates of CHD., Approach and Results: In total, 1981 men from the population-based Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), aged 42 to 60 years and free of CHD at baseline in 1984 to 1989, were investigated. Food consumption was assessed with 4-day food recording. Multivariate nutrient-density models were used to analyze isocaloric replacement of nutrients. CHD events were ascertained from national registries. Carotid atherosclerosis was assessed by ultrasonography of the common carotid artery intima-media thickness in 1015 men. During the average follow-up of 21.4 years, 183 fatal and 382 nonfatal CHD events occurred. SFA or trans fat intakes were not associated with CHD risk. In contrast, monounsaturated fat intake was associated with increased risk and polyunsaturated fat intake with decreased risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. The associations with carotid atherosclerosis were broadly similar, whereas the associations with nonfatal CHD were weaker., Conclusions: Our results suggest that SFA intake is not an independent risk factor for CHD, even in a population with higher ranges of SFA intake. In contrast, polyunsaturated fat intake was associated with lower risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. Further investigation on the effect of monounsaturated fat on the CHD risk is warranted., (© 2014 American Heart Association, Inc.)

Background: Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse., Methods and Results: To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMT(mean), IMT(max), and IMT(mean-max)), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11,590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75 × 10(-7) for IMT(max); replication P=7.24×10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53 × 10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83 × 10(-4), n=82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138)., Conclusions: This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent.

Objective: In culture studies matrix metalloproteinase (MMP)-8 thins the protecting fibrous cap of the atherosclerotic plaque thereby increasing its vulnerability. Results on the association of serum MMP-8 concentrations and cardiovascular diseases (CVD) are, however, scarce and contradictory., Methods and Results: We analyzed the association between CVD or subclinical atherosclerosis and serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations of 1018 men with the follow-up time of 10 years. MMP-8 concentrations or MMP-8/TIMP-1 ratios were higher in men with prevalent CVD or subclinical atherosclerosis at baseline than those without. In men free of CVD at baseline, MMP-8 concentrations associated with acute myocardial infarction, death from coronary heart disease (CHD), CVD, or from any cause with relative risks (RR) (95% CI) of 1.138 (1.009 to 1.284), 1.188 (1.034 to 1.365), 1.171 (1.026 to 1.338), and 1.136 (1.018 to 1.269), respectively, and MMP-8/TIMP-1 ratio with CHD death with an RR of 1.206 (1.028 to 1.414) per standard deviation (SD) increase. In men with no prevalent CVD but with subclinical atherosclerosis at baseline, elevated serum MMP-8 concentration predicted CVD death with an RR of 3.03 (1.09 to 8.44). TIMP-1 concentrations alone had no predictive value., Conclusions: The results indicate that serum MMP-8 concentrations are elevated in prevalent or subclinical atherosclerosis and associate with the worst cardiovascular outcome.

Objective: High-density lipoprotein (HDL) cholesterol correlates inversely with the risk of coronary heart disease (CHD). The precise antiatherogenic mechanisms of HDL subspecies are not thoroughly elucidated. We studied the relationship between carotid intima-media thickness (IMT) and HDL subspecies distribution in Finnish families with low HDL cholesterol and premature CHD., Methods and Results: Altogether, 148 members of Finnish low-HDL families and 133 healthy control subjects participated in our study. HDL particle size was significantly smaller in affected family members (HDL < or =10th Finnish age-sex specific percentile) compared with unaffected family members and control subjects (9.1+/-0.04 nm versus 9.5+/-0.05 nm, P<0.0001, versus 9.8+/-0.03 nm, P<0.0001 [mean+/-SE]). Large HDL2b particles as well as prebeta-HDL concentration were significantly decreased among the affected family members. Mean IMT was significantly higher in the affected family members than in the control subjects (0.85+/-0.01 mm versus 0.79+/-0.01 mm; P<0.0001). Age, HDL2b, systolic blood pressure, and prebeta-HDL were significant independent determinants of mean IMT., Conclusions: The decreased levels of HDL2b and prebeta-HDL reflect the potentially efflux-deficient HDL subspecies profile in the affected low-HDL family members. Decreased HDL particle size caused by the decrease of plasma concentration of HDL2b and decreased prebeta-HDL levels correlate with increased IMT.

Objective: Mercury has been suggested to have negative effects on cardiovascular health. We investigated the effects of high mercury content in hair on the risk of acute coronary events and cardiovascular and all-cause mortality in men from eastern Finland., Methods and Results: The population-based prospective Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) cohort of 1871 Finnish men aged 42 to 60 years and free of previous coronary heart disease (CHD) or stroke at baseline was used. During an average follow-up time of 13.9 years, 282 acute coronary events and 132 cardiovascular disease (CVD), 91 CHD, and 525 all-cause deaths occurred. Men in the highest third of hair mercury content (>2.03 microg/g) had an adjusted 1.60-fold (95% CI, 1.24 to 2.06) risk of acute coronary event, 1.68-fold (95% CI, 1.15 to 2.44) risk of CVD, 1.56-fold (95% CI, 0.99 to 2.46) risk of CHD, and 1.38-fold (95% CI, 1.15 to 1.66) risk of any death compared with men in the lower two thirds. High mercury content in hair also attenuated the protective effects of high-serum docosahexaenoic acid plus docosapentaenoic acid concentration., Conclusions: High content of mercury in hair may be a risk factor for acute coronary events and CVD, CHD, and all-cause mortality in middle-aged eastern Finnish men. Mercury may also attenuate the protective effects of fish on cardiovascular health.