Atherosclerosis In Middle-aged Men Research Articles

Hyperhomocysteinemia as a subclinical predictor of multifocal atherosclerosis in middle aged men

Background and Aims: Purpose: to determine the role of hyperhomocysteinemia (HHC) as a predictor of multifocal atherosclerosis in middle-aged men at the subclinical stage.

Relationship between Serum Osteocalcin and Carotid Atherosclerosis in Middle-Aged Men in China: A Cross-Sectional Study.

Background and Purpose Numerous investigations found that there exists a close relationship between serum osteocalcin and incurrence of atherosclerosis, but studies investigating the effect of serum osteocalcin on carotid atherosclerosis are very limited. Our study is aimed at investigating the role of osteocalcin in carotid atherosclerosis in middle-aged men in China. Methods A total of 335 male middle-aged participants (40-60, 52.4 ± 3.87 years averagely) were enrolled from the institute. The carotid intima-media thicknesses (CIMT) of each subject were measured. All subjects were included either in the carotid atherosclerosis (AS) group or the control group according to the CAS diagnosis criteria. Serum osteocalcin and other markers of each patient were assessed following standard laboratory tests protocol. Results 135 subjects were included in AS group, and 199 subjects were included in control group. The average osteocalcin level in AS group was 18.71 ± 6.20 ng/ml and was significantly different from that in control group, which was 20.38 ± 7.19 ng/ml (p=0.039). Logistic regression analysis revealed that OCN (standardized β=-0.024, p=0.013) and FINS (standardized β=-0.065, p=0.010) were independently and inversely associated with the carotid atherosclerosis, while FPG (standardized β=0.538, p=0.006) was independently and positively associated with the carotid atherosclerosis. Conclusion Our study suggests that OCN is independently related to carotid atherosclerosis in middle-aged male individuals.

In silico epigenetics of metal exposure and subclinical atherosclerosis in middle aged men: pilot results from the Aragon Workers Health Study.

We explored the association of metal levels with subclinical atherosclerosis and epigenetic changes in relevant biological pathways. Whole blood DNA Infinium Methylation 450 K data were obtained from 23 of 73 middle age men without clinically evident cardiovascular disease (CVD) who participated in the Aragon Workers Health Study in 2009 (baseline visit) and had available baseline urinary metals and subclinical atherosclerosis measures obtained in 2010-2013 (follow-up visit). The median metal levels were 7.36 µg g-1, 0.33 µg g-1, 0.11 µg g-1 and 0.07 µg g-1, for arsenic (sum of inorganic and methylated species), cadmium, antimony and tungsten, respectively. Urine cadmium and tungsten were associated with femoral and carotid intima-media thickness, respectively (Pearson's r = 0.27; p = 0.03 in both cases). Among nearest genes to identified differentially methylated regions (DMRs), 46% of metal-DMR genes overlapped with atherosclerosis-DMR genes (p < 0.001). Pathway enrichment analysis of atherosclerosis-DMR genes showed a role in inflammatory, metabolic and transport pathways. In in silico protein-to-protein interaction networks among proteins encoded by 162 and 108 genes attributed to atherosclerosis- and metal-DMRs, respectively, with proteins known to have a role in atherosclerosis pathways, we observed hub proteins in the network associated with both atherosclerosis and metal-DMRs (e.g. SMAD3 and NOP56), and also hub proteins associated with metal-DMRs only but with relevant connections with atherosclerosis effectors (e.g. SSTR5, HDAC4, AP2A2, CXCL12 and SSTR4). Our integrative in silico analysis demonstrates the feasibility of identifying epigenomic regions linked to environmental exposures and potentially involved in relevant pathways for human diseases. While our results support the hypothesis that metal exposures can influence health due to epigenetic changes, larger studies are needed to confirm our pilot results.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.

Association of body flexibility and carotid atherosclerosis in Japanese middle-aged men: a cross-sectional study

ObjectiveThis study examined the associations of body flexibility with carotid arterial remodelling, including intima–media thickness (IMT) and plaque formation in middle-aged men.MethodsThe subjects of this cross-sectional study included 1354 Japanese...

Long-term effect of different physical activity levels on subclinical atherosclerosis in middle-aged men: a 25-year prospective study.

BackgroundThe purpose of the study was to investigate the influence of lifetime physical activity (PA) on selected indices of atherosclerosis in longitudinal observation of middle-aged men.MethodsThe subject of the study was a cohort of 101 men (mean age 59,7±9,0 years), free of cardiovascular symptoms and treatment, participating in follow-up examinations in the years 1985/90-2011/12. Self-report PA was assessed by interviewer-administered Seven-Day PA Recall and Historical PA questionnaire. Subclinical atherosclerosis was measured by assessing the coronary artery calcification (CAC) according to Agatston's method using multi-slice computed tomography; the carotid intima-media thickness (IMT) using high-resolution B-mode ultrasound; and the reactive hyperemia index (RHI) using peripheral arterial tonometry (EndoPAT2000). The participants were initially divided into three groups according to tertiles of exercise-related energy expenditure (EE) in kcal/week at baseline, i.e. <2050 (low-to-moderate; n = 33), 2050–3840 (high; n = 34), >3840 (very high; n = 34).ResultsThe low-to-moderate, high and very high PA groups were comparable in terms of age and atherosclerosis risk factors at baseline. No linear relationship was found between PA and CAC, IMT and RHI. Men who maintained low-to-moderate (n = 26), high (n = 21) and very high (n = 15) PA level had the mean CAC of 286.1±361.9, 10.7±28.9, and 106.1±278.3 (p<0.001 for low-to moderate vs high; p<0.05 for low-to-moderate vs very high); the mean IMT of 0.751±0.19 mm, 0,641±0.26 mm, and 0.750±0.60 mm (p>0.05); and the mean RHI of 1.69±0.4, 2.00±0.4, and 2.13±0.5 (p for trend = 0.050), respectively. No cases of CAC>400, IMT ≥0.9 and RHI<1.67 were noted only among men with maintained high PA level. At final examination men with high and very high PA had more favorable cardiometabolic profile than men with lower PA.ConclusionsMaintaining regular high PA level through young and middle adulthood may protect against atherosclerosis as measured by CAC, IMT and RHI.

Influence of physical activity level on subclinical atherosclerosis in middle-aged men. Results of longitudinal over 25 years prospective observation

Influence of physical activity level on subclinical atherosclerosis in middle-aged men. Results of longitudinal over 25 years prospective observation

Intelligence in early adulthood and subclinical atherosclerosis in middle-aged men: the Vietnam Experience Study

BackgroundPeople with higher intelligence in early life have a lower subsequent risk of coronary heart disease events, but the explanation for these observations is unclear.AimsTo examine whether intelligence in early...

Effects of Testosterone Undecanoate on Cardiovascular Risk Factors and Atherosclerosis in Middle-Aged Men with Late-Onset Hypogonadism and Metabolic Syndrome: Results from a 24-month, Randomized, Double-Blind, Placebo-Controlled Study

Effects of Testosterone Undecanoate on Cardiovascular Risk Factors and Atherosclerosis in Middle-Aged Men with Late-Onset Hypogonadism and Metabolic Syndrome: Results from a 24-month, Randomized, Double-Blind, Placebo-Controlled Study

Effects of Testosterone Undecanoate on Cardiovascular Risk Factors and Atherosclerosis in Middle-Aged Men with Late-Onset Hypogonadism and Metabolic Syndrome: Results from a 24-month, Randomized, Double-Blind, Placebo-Controlled Study

Longitudinal studies have demonstrated that male hypogonadism could be considered a surrogate marker of incident cardiovascular disease. To evaluate the effects of parenteral testosterone undecanoate (TU) in outclinic patients with metabolic syndrome (MS) and late-onset hypogonadism (total testosterone (T) at or below 11nmol/L or free T at or below 250pmol/L). This is a randomized, double-blind, double-dummy, placebo-controlled, parallel group, single-center study. Fifty patients (mean age 57±8) were randomized (4:1) to receive TU 1,000mg (every 12 weeks) or placebo (PLB) gel (3-6 g/daily) for 24 months. Homeostasis model assessment index of insulin resistance (HOMA-IR), carotid intima media thickness (CIMT), and high-sensitivity C-reactive protein (hsCRP). At baseline, all patients fulfilled the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International Diabetes Federation (IDF) criteria for the definition of MS. An interim analysis conducted at 12 months showed that TU markedly improved HOMA-IR (P < 0.001), CIMT (P < 0.0001), and hsCRP (P<0.001) compared with PLB; thus, all patients were shifted to TU treatment. After 24 months, 35% (P < 0.0001) and 58% (P < 0.001) of patients still presented MS as defined by NCEP-ATPIII and IDF criteria, respectively. Main determinants of changes were reduction in waist circumference (P<0.0001), visceral fat mass (P<0.0001), and improvement in HOMA-IR without changes in body mass index (BMI). TU reduced fasting glucose, waist circumference, and improved surrogate markers of atherosclerosis in hypogonadal men with MS. Resumption and maintenance of T levels in the normal range of young adults determines a remarkable reduction in cardiovascular risk factors clustered in MS without significant hematological and prostate adverse events.

Military combat and burden of subclinical atherosclerosis in middle aged men: The ARIC Study

Background Studies of the cardiovascular consequences of combat stress are few and inconclusive. Objective The association between combat exposure and subclinical atherosclerosis at Atherosclerosis Risk in Communities (ARIC) Study visits 1 (1987–1989) and 2 (1990–1992) was assessed among 5347 men from four U.S. communities. Methods Measured an average of 36 years after military entry, carotid intima-media thickness (CIMT) and carotid plaque among non-combat veterans ( n = 2127) were compared with non-veterans ( n = 2042) and veterans reporting combat experience ( n = 1178). Results Compared to non-combat veterans, non-veterans (risk difference (RD): 10.61; 95% confidence interval (CI): 0.81, 20.41) and combat veterans (RD: 12.79; 95% CI: 0.72, 24.86) had higher age-adjusted mean CIMT. Differences remained for combat veterans after adjustment for race, father's education and age at service entry but not years of service and for non-veterans after adjustment for race but not father's education. No differences in carotid plaque were noted. Conclusion Results do not suggest that combat has a long-term detrimental effect on subclinical atherosclerosis among men.

Military combat and burden of subclinical atherosclerosis in middle aged men: The ARIC Study

Military combat and burden of subclinical atherosclerosis in middle aged men: The ARIC Study

Binge drinking and the progression of atherosclerosis in middle-aged men: An 11-year follow-up

ObjectiveThere is limited knowledge on drinking patterns and the progression of atherosclerosis. Previous studies have shown conflicting results between alcohol consumption and atherosclerotic progression. We investigated the association between the pattern of binge drinking and the 11-year progression of carotid atherosclerosis in a population-based sample of middle-aged men. Methods and resultsThis study is a part of the FinDrink Study, based on the Kuopio Ischemic Heart Disease Risk Factor Study. We investigated the effect of drinking patterns on the changes in maximum and mean intima-media thickness, including changes in maximum plaque height in 751 participants as measured by carotid ultrasound. The increased atherosclerosis progression was statistically significant among those men with binge drinking of ≥6 drinks per session (22.4% of total number of participants) using different covariates in different models according to the mean increase in maximum intima-media thickness (Model 1, p=0.008; Model 2, p=0.031, Model 3, p=0.037) and the mean increase in maximum plaque height (Model 1, p=0.002; Model 2, p=0.012, Model 3, p=0.017). ConclusionOur study shows that binge drinking was associated with an increased atherosclerosis progression during an 11-year follow-up in middle-aged men, independent of the total alcohol consumption.

A Comparison of Aerobic Exercise and Resistance Training in Patients With and Without Chronic Kidney Disease

The morbidity and mortality associated with chronic kidney disease (CKD) are primarily caused by atherosclerosis and cardiovascular disease, which may be in part caused by inflammation and oxidative stress. Aerobic exercise and resistance training have been proposed as measures to combat obesity, inflammation, endothelial dysfunction, oxidative stress, insulin resistance, and progression of CKD. In non-CKD patients, aerobic exercise reduces inflammation, increases insulin sensitivity, decreases microalbuminuria, facilitates weight loss, decreases leptins, and protects against oxidative injury. In nondialysis CKD, aerobic exercise decreases microalbuminuria, protects from oxidative stress, and may increase the glomerular filtration rate (GFR). Aerobic exercise in hemodialysis patients has been reported to enhance insulin sensitivity, improve lipid profile, increase hemoglobin, increase strength, decrease blood pressure, and improve quality of life. Resistance training, in the general population, decreases C-reactive protein, increases insulin sensitivity, decreases body fat content, increases insulin-like growth factor-1 (IGF-1), and decreases microalbuminuria. In the nondialysis CKD population, resistance training has been reported to reduce inflammation, increase serum albumin, maintain body weight, increase muscle strength, increase IGF-1, and increase GFR. Resistance training in hemodialysis increases muscle strength, increases physical functionality, and improves IGF-1 status. Combined aerobic exercise and resistance training during dialysis improves muscle strength, work output, cardiac fitness, and possibly dialysis adequacy. There is a need for more investigation on the role of exercise in CKD. If the benefits of aerobic exercise and strength training in non-CKD populations can be shown to apply to CKD patients as well, renal rehabilitation will begin to play an important role in the approach to the treatment, prevention, and slowed progression of CKD.

Fish consumption and early atherosclerosis in middle-aged men

To investigate the association between fish consumption and early atherosclerosis, we analyzed the relationship between fish consumption and average intima-media thickness (AveIMT) by carotid ultrasound in middle-aged Japanese men. Participants were 250 randomly selected, community-based Japanese men aged 40 to 49 years without a prior history of cardiovascular disease. AveIMT was calculated from the mean of 1-cm lengths of both the right and the left carotid arteries at 8 locations. A lifestyle survey was carried out using a self-administered questionnaire including the frequency of fish intake. There were 147 men in the fewer than 4 times per week fish consumption group and 103men in the 4 or more times per week group. The mean AveIMT was significantly higher in the low fish consumption group than in the high fish consumption group (0.623 ± 0.068 vs 0.605 ± 0.065 mm, P = .03). After adjustment for age, waist circumference, pack-years of smoking, alcohol consumption, diabetes, and lipid-lowering medications, the significant difference in the AveIMT between the 2 groups remained. However, after further adjustment for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and C-reactive protein in the model, the significant difference disappeared. Fish consumption may be protective against early atherosclerosis in middle-aged men, probably through its beneficial effects on inflammation.

Sex differences in the relation of HDL cholesterol to progression of carotid intima-media thickness: The Los Angeles Atherosclerosis Study

Epidemiologic studies have revealed that the protective association of high-density lipoprotein cholesterol (HDL-C) with CHD is stronger in older men and younger women. We aimed to investigate sex differences in the relation of HDL-C to progression of carotid intima-media thickness (IMT) (an indicator of subclinical atherosclerosis) in middle age. IMT progression and serum HDL-C were determined for a cohort of 500 women and men aged 40–60 years over three examinations (1.5-year intervals). IMT at baseline was inversely associated with serum levels of HDL-C and the associations were comparable in women and men. However, in multivariate longitudinal growth models adjusting for potential confounders, IMT progression was inversely associated with serum levels of HDL-C in men, but directly associated in women ( p = 0.0007 for interaction). Our results suggest that although HDL-C was protective against progression of carotid atherosclerosis in middle-aged men, anti-atherogenic effects of HDL may diminish in women around the age of menopause.

Machine Learning Methods for Knowledge Discovery in Medical Data on Atherosclerosis

Machine learning techniques are methods that given a training set of examples infer a model for the categories of the data, so that new (unknown) examples could be assigned to one or more categories by pattern matching within the model. The data from follow-up studies with repeated collection of the same type of data are very suitable for this analysis. Machine learning algorithms belonging to a variety of paradigms have been applied to knowledge discovery on medical data. All the used algorithms belong to the supervised learning paradigm. Several algorithms have been tested, trying to cover most of the kinds of supervised learning. Two kinds of experiments have been carried out. The first is intended to discover associations between attributes. The second kind is intended to test prediction of future disorders. For the experiments in this paper the data used was from the twenty years lasting primary preventive longitudinal study of the risk factors (RF) of atherosclerosis in middle aged men. Study is named STULONG (LONGitudinal STUdy). The results show that some methods predict some disorders better than others, so it is interesting to use all the algorithms at a time and consider the result confidence based upon the known tendency of each method. The machine learning algorithms have been also used in the prediction of death cause, obtaining poor results in this case, maybe due to the small amount of information (entries) of this type in the dataset.

Blood leukocyte count is a risk factor for intima-media thickening and subclinical carotid atherosclerosis in middle-aged men

Leukocytosis is known to predict future cardiovascular events even in subjects without coronary heart disease (CHD), but its association with early atherosclerotic changes has remained less certain. The aim of the present study was to investigate how the blood leukocyte count compares with several other risk factors for CHD in determining carotid artery intima-media thickness (IMT) and subclinical carotid atherosclerosis in a population sample. Both carotid arteries were investigated with high-resolution B-mode ultrasound in a community-based sample of 219 randomly selected men aged 50–59 years to calculate the mean maximum IMT (MMax IMT) of 12 standard sites. Risk factor assessment included several traditional biochemical risk factors, blood pressure, maximal oxygen consumption and work load on ergometry, life-style habits and hematologic parameters. As genetic determinants, apolipoprotein E and A-IV polymorphisms were studied. According to multivariate regression analysis, age ( P < 0.0001), blood leukocyte count ( P < 0.0001) and systolic blood pressure ( P < 0.042) were the only significant predictors of MMax IMT. MMax IMT increased linearly from the lowest tertile of blood leukocyte count (1.14 ± 0.20 mm) to the second (1.18 ± 0.25 mm) and to the highest tertile (1.25 ± 0.27 mm, P = 0.019). This difference remained significant after adjustment with age, systolic blood pressure and smoking ( P = 0.032). Leukocytes seem to have an independent role in the early arterial damage and they may reflect subclinical disease. This implies that leukocyte count is undervalued in the diagnostics and prognostics of carotid atherosclerosis.

Socioeconomic differences in the progression of carotid atherosclerosis in middle-aged men and women with subclinical atherosclerosis in Sweden

While the persistence of socioeconomic differences in cardiovascular disease (CVD) has been recognized for many years, less is known about whether socioeconomic factors are of importance to CVD before symptoms of the disease appear. In this study the associations among educational level, occupational status and progression of atherosclerosis were investigated in 1016 Swedish middle-aged men and women with signs of subclinical atherosclerosis, i.e., carotid plaque (defined as focal intima-media thickness (IMT) >1.2 mm). IMT in the common carotid artery (CCA) and in the carotid bifurcation area, as well as carotid plaque score, was determined by B-mode ultrasound. Results showed only weak associations between educational level, occupational status and age-, sex- and baseline IMT-adjusted progression of IMT in the CCA. However, in the age, sex- and baseline IMT-adjusted analyses, those in unskilled manual occupations showed a significantly higher yearly progression of carotid IMT in the bifurcation area compared to those in high- or medium-level non-manual occupations. Those with primary education tended to show a higher yearly progression of carotid IMT in the bifurcation area compared to those with completed secondary education. After adjustment for risk factors, the magnitude of these associations were somewhat attenuated. Similar patterns of associations were seen for the change of carotid plaque score. We conclude that low socioeconomic status (SES) is associated with progression of atherosclerosis in a middle-aged population with signs of subclinical atherosclerosis. Even though socioeconomic differences in cardiovascular risk factor levels could explain part of the found differences in progression rate in women, the mechanisms involved remain to be further established.

Increased Carotid Atherosclerosis in Andropausal Middle-Aged Men

This study examined the association between carotid artery intima-media thickness (IMT), serum sex hormone levels, and andropausal symptoms in middle-aged men. Male sex hormones may play a dual role in the pathogenesis of atherosclerosis in men by carrying both proatherogenic and atheroprotective effects. 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. 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. 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.

Circulating oxidized low-density lipoprotein and common carotid artery intima-media thickness in a random sample of middle-aged men.

Circulating oxidized low-density lipoprotein (oxLDL) has been suggested to play an important role in atherosclerosis development. According to previous observations, oxLDL correlates with clinically manifest coronary and carotid artery disease. We investigated the association between the oxLDL concentration measured directly in plasma and common carotid artery intima-media thickness (IMT) in a population-based, case-control study in middle-aged men from Southern Finland. oxLDL was determined in 214 men by a commercially available sandwich ELISA test (Mercodia). Carotid artery IMT was measured at 12 standardized segments by B-mode ultrasonography (at the near and far wall of the left and right common carotid arteries, bifurcations and internal carotid arteries), and the overall mean maximum IMT (MMaxIMT) was calculated. The MMaxIMT of the carotid arteries was significantly associated with circulating oxLDL (r(s) = 0.16, p = 0.018). In a stepwise multiple regression model with MMaxIMT as dependent variable and systolic blood pressure, smoking, oxLDL, HDL cholesterol and apolipoprotein B as covariates, systolic blood pressure (beta = 0.22, p < 0.001), oxLDL (beta = 0.15, p = 0.022) and smoking (beta = 0.17, p = 0.014) showed an independent association with IMT (R(2) = 0.10, p < 0.001). Our results show that oxLDL measured directly from plasma is independently associated with subclinical carotid artery atherosclerosis in middle-aged men.