Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Preconception metabolic indicators predict gestational diabetes and offspring birthweight

Pregnancy conditions such as gestational diabetes (GDM) and macrosomia lead to an increased risk of diabetes and cardiovascular disease in the offspring, perpetuating a cycle of poor health. We hypothesized that (1) pre-pregnancy indicators of metabolism would be associated with GDM and birthweight; and (2) the lipid accumulation product (LAP; incorporating waist circumference and triglycerides) and visceral adiposity index (VAI; incorporating waist circumference, triglycerides, and HDL-c) would be better predictors of GDM and birthweight than other indicators. Data from the Cardiovascular Risk in Young Finns Study were linked to the Finnish birth registry for 349 women. BMI, triglycerides, waist circumference, insulin, HOMA-IR, LAP, and VAI at the visit prior to the pregnancy were examined as predictors of GDM and large-for-gestational-age (LGA) using logistic regression with adjustment for age, parity, and smoking. Waist circumference was the strongest predictor of GDM (adjusted odds ratio [aOR] 1.66, 95% confidence interval 1.16–2.38) and LGA (aOR 1.41, 1.00–1.99). For GDM, all markers had similar discrimination; for LGA, the area under the receiver operating curve for waist circumference was significantly higher than for BMI (p?相似文献   

Increased carotid atherosclerosis in andropausal middle-aged men

OBJECTIVES: This study examined the association between carotid artery intima-media thickness (IMT), serum sex hormone levels, and andropausal symptoms in middle-aged men. BACKGROUND: Male sex hormones may play a dual role in the pathogenesis of atherosclerosis in men by carrying both proatherogenic and atheroprotective effects. METHODS: We studied 239 40- to 70-year-old men (mean +/- SD: 57 +/- 8 years) who participated in the Turku Aging Male Study and underwent serum lipid and sex hormone measurements. Ninety-nine men (age 58 +/- 7 years) were considered andropausal (i.e., serum testosterone <9.8 nmol/l or luteinizing hormone [LH] >6.0 U/l and testosterone in the normal range), and in both situations, they had subjective symptoms of andropause (a high symptom score in questionnaire). Three were excluded because of diabetes. The rest of the men (age 57 +/- 8 years) served as controls. Carotid IMT was determined using high-resolution B-mode ultrasound, and serum testosterone, estradiol (E2), LH, and sex hormone-binding globulin were measured using standard immunoassays. RESULTS: Andropausal men had a higher maximal IMT compared with controls in the common carotid (1.08 +/- 0.34 vs. 1.00 +/- 0.23, p < 0.05) and in the carotid bulb (1.44 +/- 0.48 vs. 1.27 +/- 0.35, p = 0.003). Common carotid IMT correlated inversely with serum testosterone (p = 0.003) and directly with LH (p = 0.006) in multivariate models adjusted for age, total cholesterol, body mass index, blood pressure, and smoking. CONCLUSIONS: Middle-aged men with symptoms of andropause, together with absolute or compensated (as reflected by high normal to elevated LH) testosterone deficiency, show increased carotid IMT. These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men.     

Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia

OBJECTIVE: The goal of this study was to examine the relationship between plasma asymmetric dimethylarginine (ADMA) level and hyperemic myocardial blood flow (MBF) in subjects with borderline hypertension (BHT) and familial hypercholesterolemia (FH). METHODS: Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase that may modulate vascular function.We measured plasma ADMA levels and myocardial flow in 77 young men (mean age 35 +/- 5 years), including 47 healthy controls, 16 men with BHT, and 14 men with FH. Basal and dipyridamole-induced myocardial flow was measured using positron emission tomography. Plasma ADMA levels were measured using high-pressure liquid chromatography. RESULTS: Asymmetric dimethylarginine levels were significantly elevated in the BHT group compared with controls (0.59 +/- 0.13 micromol/l vs. 0.43 +/- 0.12 micromol/l, p < 0.001), and they had significantly lower dipyridamole flow (2.85 +/- 1.20 ml/min/g vs. 3.69 +/- 1.68 ml/min/g, p < 0.05). In a multivariate regression model adjusted for the study group, dipyridamole flow was inversely associated with ADMA (p < 0.05), age (p < 0.05), and apolipoprotein B concentration (p < 0.05). CONCLUSIONS: We conclude that plasma ADMA concentration is related to dipyridamole-induced vasodilatory function in young men, independently of blood pressure elevation and hypercholesterolemia. Subjects with BHT have significantly increased plasma ADMA levels, which may partly explain the impaired hyperemic MBF in this condition.     

Body-image dissatisfaction is strongly associated with chronic dysphoria

Background

Individual depressive symptoms may contribute to the risk of chronic depression. This study aimed to explore which symptoms predict chronic dysphoria, a hallmark of depression.

Methods

1057 participants from the population-based Young Finns study were examined for four times during a 16-year period. Those with a modified Beck’s Depression Inventory score in the upper third at all four screenings were considered to have chronic dysphoria (n=135). Participants with only one high depression score formed the reference group of transient dysphoria (n=179). Individual items of the Inventory were analyzed in terms of their association with dysphoria status and chronicity, controlling for potential confounding factors, such as personality assessed using the Temperament and Character Inventory.

Results

Body-image dissatisfaction was strongly associated with chronically elevated dysphoria (Bonferroni-corrected p=0.006). The degree of body-image dissatisfaction was associated with the probability for chronic dysphoria in a dose–response manner, with the estimated probability ranging from 0.01 to 0.60 as a function of item response. The association remained after adjustments for a wide range of personality characteristics.

Limitations

The study relied on self-reports of mood and personality, and lacked information on external opinion on participants appearances. The requirement of full time-series data may have resulted in attrition-related bias.

Conclusions

Body-image dissatisfaction was a strong predictor of chronic depression characterized by dysphoria. This finding suggests that dysfunctional attitude towards oneself might represent a potentially important target for cognitive therapies and preventive interventions.     

Role of Childhood Food Patterns on Adult Cardiovascular Disease Risk

Accumulating evidence indicates that childhood nutrition plays a role in the adulthood cardiovascular health. A lifelong tracking of dietary habits, following a long-term exposure to unhealthy dietary patterns or independent effects, is a potential effect-mediating mechanism. Dietary patterns have been studied by data-driven and hypothesis-based approaches. Typically, either data-driven healthy or prudent childhood dietary patterns have been characterized and found to be associated with lower adulthood cardiovascular disease (CVD) risk in the published cohort studies. With regard to the individual food groups or food quality indices, intakes particularly of vegetables and fruits (or fiber indicating plant food intake) and polyunsaturated fatty acids have shown protective effects. The evidence which could confirm the long-term healthiness of a hypothesis-based Mediterranean diet is limited, requiring further investigation. Overall, the recent literature strengthens the view that a healthy childhood diet is associated with lowered adulthood CVD risk.     

Arterial pulse wave velocity in relation to carotid intima-media thickness, brachial flow-mediated dilation and carotid artery distensibility: the Cardiovascular Risk in Young Finns Study and the Health 2000 Survey

ObjectiveIncreased arterial pulse wave velocity (PWV) is a strong predictor of cardiovascular events and mortality. The data regarding the relationships between PWV and other indices of vascular damage is limited and partly controversial. We conducted the present study to examine PWV in relation to non-invasive measures of early atherosclerosis (brachial flow-mediated dilation [FMD], carotid intima-media thickness [IMT]) and local arterial stiffness (carotid artery distensibility [Cdist]).MethodsThe study population consisted of 1754 young adults (aged 30–45 years, 45.5% males) participating in the Cardiovascular Risk in Young Finns Study (YFS), and of 336 older adults (aged 46–76 years, 43.2% males) participating in the Health 2000 Survey. FMD was measured only in the YFS cohort. FMD, IMT and Cdist were assessed by ultrasound, and PWV was measured using the whole-body impedance cardiography device.ResultsIn young adults, FMD and IMT were not associated with PWV independently of cardiovascular risk factors. Moreover, FMD status was not found to modulate the association between cardiovascular risk factors and PWV. In older adults, PWV and IMT were directly and independently associated (β = 1.233, p = 0.019). In both cohorts, PWV was inversely related with Cdist, and this relation remained significant (p < 0.04) in models adjusted for cardiovascular risk factors.ConclusionsThe current findings suggest that PWV reflects a different aspect of vascular damage than FMD or IMT in young adults, whereas in older adults the information provided by PWV and IMT may be, to some extent, similar as regards subclinical vascular damage. The present observations also suggest that PWV and Cdist represent, at least in part, a similar adverse vascular wall process.