Cardiovascular Disease Risk In Men Research Articles

Leptin Predicts Diabetes but Not Cardiovascular Disease

OBJECTIVE—To clarify the association of circulating levels of leptin with risk for cardiovascular disease (CVD) events and new-onset diabetes in men and women.RESEARCH DESIGN AND METHODS—We related baseline leptin levels to CVD events (n = 864) and incident diabetes (n = 289) in an elderly population (n = 5,672) over 3.2 years of follow-up.RESULTS—In treatment-, age-, and country-adjusted models, leptin was not associated with risk of CVD in men (hazard ratio 1.02 [95% CI 0.90–1.16] per unit log-leptin increase) or women (1.05 [0.91–1.20]) but was associated with risk of diabetes in men (2.75 [2.14–3.52]) and women (1.54 [1.22–1.94]). After adjusting for classic risk factors and BMI, C-reactive protein, and glucose, the diabetes association retained significance in men (1.85 [1.30–2.63]) but not in women (0.89 [0.64–1.26]).CONCLUSIONS—Leptin, similar to other markers of adiposity in general, is more strongly related to risk of diabetes than CVD in the elderly.

THE EFFECT OF NANDROLONE DECANOATE THERAPY ON LIPOPROTEIN(A) AND HOMOCYSTEINE LEVELS IN HEMODIALYSIS PATIENTS

An important sex difference in body fat distribution is generally observed. Men are usually characterized by the android type of obesity, with accumulation of fat in the abdominal region, whereas women often display the gynoid type of obesity, with a greater proportion of their body fat in the gluteal-femoral region. Accordingly, the amount of fat located inside the abdominal cavity (intra-abdominal or visceral adipose tissue) is twice as high in men compared to women. This sex difference has been shown to explain a major portion of the differing metabolic profiles and cardiovascular disease risk in men and women. Association studies have shown that circulating androgens are negatively associated with intra-abdominal fat accumulation in men, which explains an important portion of the link between low androgens and features of the metabolic syndrome. In women, the low circulating sex hormone-binding globulin (SHBG) levels found in abdominal obesity may indirectly indicate that elevated free androgens are related to increased visceral fat accumulation. However, data on non SHBG-bound and total androgens are not unanimous and difficult to interpret for total androgens. These studies focusing on plasma levels of sex hormones indirectly suggest that androgens may alter adipose tissue mass in a depot-specific manner. This could occur through site-specific modulation of preadipocyte proliferation and/or differentiation as well as lipid synthesis and/or lipolysis in mature adipocytes. Recent results on the effects of androgens in cultured adipocytes and adipose tissue have been inconsistent, but may indicate decreased adipogenesis and increased lipolysis upon androgen treatment. Finally, adipose tissue has been shown to express several steroidogenic and steroid-inactivating enzymes. Their mere presence in fat indirectly supports the notion of a highly complex enzymatic system modulating steroid action on a local basis. Recent data obtained in both men and women suggest that enzymes from the aldoketoreductase 1C family are very active and may be important modulators of androgen action in adipose tissue.

Biomarkers of cardiovascular disease risk in 40–65-year-old men performing recommended levels of physical activity, compared with sedentary men

Objective:Both the UK Department of Health and the US Centers for Disease Control and Prevention have recommended at least 30 minutes of moderate-intensity physical activity on most days for health....

A prospective community-population-registry–based cohort study of the association between betel-quid chewing and cardiovascular disease in men in Taiwan (KCIS no. 19)

BackgroundBetel-quid chewing, a recognized risk factor for oral cancer, was shown to be a contributory cause of metabolic syndrome in humans, which implies a greater likelihood of developing cardiovascular disease (CVD) among those with the betel habit. ObjectiveThis study investigated the effect of betel chewing on the risk of developing overt CVD. DesignWe used the prospective cohort data derived from a community-population-registry–based integrated screening program to quantify the effect of betel-quid chewing on the incidence of newly diagnosed CVD by classifying the study population into either exposed or nonexposed groups according to chewing status at baseline. We then followed the group free of CVD at recruitment for 2.72 y (SD = 1.52 y) to learn of new cardiovascular events. Proportional hazards regression modeling was used to estimate the magnitude of the effect of betel-quid chewing on CVD. ResultsAfter control for age and education level, ever chewers had a 23% (95% CI: 11%, 37%) greater risk of developing CVD than did never chewers; ever chewers were still at greater risk of developing CVD by 24% (95% CI: 11%, 39%) after further adjustment for age, education, and other significant confounders. Significant dose-response relations were found for betel-quid chewing (P < 0.05, trend test) after adjustment for other significant variables. ConclusionThe habit of chewing betel nut was shown to have independent dose effects to predict increases in the risk of CVD in men, with the use of a prospective community-population-registry–based cohort study.

Androgens and body fat distribution

An important sex difference in body fat distribution is generally observed. Men are usually characterized by the android type of obesity, with accumulation of fat in the abdominal region, whereas women often display the gynoid type of obesity, with a greater proportion of their body fat in the gluteal-femoral region. Accordingly, the amount of fat located inside the abdominal cavity (intra-abdominal or visceral adipose tissue) is twice as high in men compared to women. This sex difference has been shown to explain a major portion of the differing metabolic profiles and cardiovascular disease risk in men and women. Association studies have shown that circulating androgens are negatively associated with intra-abdominal fat accumulation in men, which explains an important portion of the link between low androgens and features of the metabolic syndrome. In women, the low circulating sex hormone-binding globulin (SHBG) levels found in abdominal obesity may indirectly indicate that elevated free androgens are related to increased visceral fat accumulation. However, data on non SHBG-bound and total androgens are not unanimous and difficult to interpret for total androgens. These studies focusing on plasma levels of sex hormones indirectly suggest that androgens may alter adipose tissue mass in a depot-specific manner. This could occur through site-specific modulation of preadipocyte proliferation and/or differentiation as well as lipid synthesis and/or lipolysis in mature adipocytes. Recent results on the effects of androgens in cultured adipocytes and adipose tissue have been inconsistent, but may indicate decreased adipogenesis and increased lipolysis upon androgen treatment. Finally, adipose tissue has been shown to express several steroidogenic and steroid-inactivating enzymes. Their mere presence in fat indirectly supports the notion of a highly complex enzymatic system modulating steroid action on a local basis. Recent data obtained in both men and women suggest that enzymes from the aldoketoreductase 1C family are very active and may be important modulators of androgen action in adipose tissue.

The National Cholesterol Education Program–Adult Treatment Panel III, International Diabetes Federation, and World Health Organization Definitions of the Metabolic Syndrome as Predictors of Incident Cardiovascular Disease and Diabetes

The clinical value of metabolic syndrome is uncertain. Thus, we examined cardiovascular disease (CVD) and diabetes risk prediction by the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATPIII), International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome. We analyzed the risks associated with metabolic syndrome, the NCEP multiple risk factor categories, and 2-h glucose values in the San Antonio Heart Study (n = 2,559; age range 25-64 years; 7.4 years of follow-up). Both ATPIII metabolic syndrome plus age > or = 45 years (odds ratio 9.25 [95% CI 4.85-17.7]) and multiple (two or more) risk factors plus a 10-year coronary heart disease (CHD) risk of 10-20% (11.9 [6.00-23.6]) had similar CVD risk in men without CHD, as well as CHD risk equivalents. In women counterparts, multiple (two or more) risk factors plus a 10-year CHD risk of 10-20% was infrequent (10 of 1,254). However, either a 10-year CHD risk of 5-20% (7.72 [3.42-17.4]) or ATPIII metabolic syndrome plus age > or = 55 years (4.98 [2.08-12.0]) predicted CVD. ATPIII metabolic syndrome increased the area under the receiver operating characteristic curve of a model containing age, sex, ethnic origin, family history of diabetes, and 2-h and fasting glucose values (0.857 vs. 0.842, P = 0.013). All three metabolic syndrome definitions imparted similar CVD and diabetes risks. Metabolic syndrome is associated with a significant CVD risk, particularly in men aged > or = 45 years and women aged > or = 55 years. The metabolic syndrome predicts diabetes beyond glucose intolerance alone.

Sex differences in the relationships between BMI, WHR and incidence of cardiovascular disease: a population-based cohort study

Body mass index (BMI) is associated with increased incidence of cardiovascular disease (CVD). However, the risk could be very different for individuals with the same body mass. The present study explored whether regional fat distribution, as measured by waist-hip ratio (WHR), could modify the impact of BMI on the risk of CVD in men and women. Prospective population-based study. A total of 10 369 men and 16 638 women, 45-73 years old, from general population in Malmö, Sweden. All subjects were followed over 7 years for the incidences of first-ever cardiac event (CE) and ischemic stroke in relation to BMI category (<25.0, 25.0-29.9, > or =30.0) and WHR. The prevalence of overweight and obesity was 39.4 and 13.0%, respectively. During follow-up, 1280 subjects suffered a CVD event (750 CE, 530 ischemic stroke). The risk of CVD in women increased with increasing levels of WHR, irrespective of BMI category. In men, WHR (per 1 s.d. increase) was associated with increased incidence of CVD in those with normal weight (relative risk (RR)=1.24; 95% CI: 1.13-1.37) after adjustments for confounding factors. However, WHR was not related to CVD in overweight men (RR=1.06; 95%CI: 0.94-1.20) or obese men (RR=1.04; 95%CI: 0.87-1.24). A significant interaction was observed between sex and WHR on the CVD risk. The effect of WHR on incidence of CVD is modified by the overall body weight and by gender. WHR adds prognostic information on the cardiovascular risk in women at all levels of BMI, and in men with normal weight.

Incidence of Myocardial Infarction and Death in Relation to Walking-Induced Calf Pain and Plasma Levels of Inflammation-Sensitive Proteins

Walking-induced calf pain as well as levels of different inflammation-sensitive plasma proteins (ISPs) are related to cardiovascular disease (CVD). This prospective cohort study explored the relationship between ISPs and walking-related calf pain and the interrelationships between ISPs and calf pain in the prediction of death and incidence of coronary events (CE). In 5,725 apparently healthy men, 46 +/-3.0 years old, plasma concentrations of orosomucoid (alpha(1)-acid glycoprotein), alpha(1)-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. Walking-induced calf pain was assessed by questionnaire. Mortality and incidence of CE were monitored over a mean follow-up of 18 years in subjects defined by the presence of calf pain and ISP level (0 to 1 or 2 to 5 ISP(s) in the top quartile). The prevalence of calf pain (7.3%) was significantly related to age, lifestyle, and traditional risk factors of CVD and ISP levels. The risk factor-adjusted relative risks for CE, CVD- and all-cause mortality were 1.89 (CI: 1.27 to 2.82), 2.90 (CI: 1.82 to 4.62), and 2.67 (CI: 1.97 to 3.57), respectively, for men with calf pain and high ISP levels (reference: no calf pain and low ISP levels). The corresponding risk for those with calf pain and low ISP levels were 1.34 (CI: 0.91 to 1.97), 1.47 (CI: 0.90 to 2.41), and 1.31 (CI: 0.95 to 1.81), respectively. These results indicate, on the one hand, that walking-induced calf pain is associated with high ISP levels and, on the other, that the risk of CVD in men with calf pain is substantially higher in those with high ISP levels than in those with low levels.

Joint effects of physical activity, body mass index, waist circumference and waist-to-hip ratio with the risk of cardiovascular disease among middle-aged Finnish men and women

To assess joint associations of physical activity and different indicators of obesity (body mass index, waist circumference, and waist-to-hip ratio) with the risk of cardiovascular disease (CVD). The study comprised 18,892 Finnish men and women aged 25-74 years without history of coronary heart disease, stroke, or heart failure at baseline. Physical activity, different indicators of obesity, education, smoking, blood pressure, total and high-density lipoprotein cholesterol and history of diabetes were measured at baseline. An incident CVD event was defined as the first stroke or coronary heart disease event or CVD death based on national hospital discharge and mortality register data. The median follow-up time was 9.8 years. Physical activity had a strong, independent, and inverse association with CVD risk in both genders. All obesity indicators had a significant direct association with CVD risk after adjustment for age, smoking, education and physical activity. Further adjustment for the obesity-related risk factors weakened the associations and they remained statistically significant in men only. Physical activity and the obesity indicators both predicted CVD risk in men, but in women the joint effect was inconsistent. Both regular physical activity and normal weight can reduce the risk of CVD. Physical inactivity seems to have an independent effect on CVD risk, whereas obesity increases the risk partly through the modification of other risk factors.

Effort–Reward Imbalance, Overcommitment, and Measures of Cortisol and Blood Pressure Over the Working Day

Objective: To assess the biological correlates of effort–reward imbalance and overcommitment to work using measurements over the working day. Methods: Participants were 197 working men and women aged 45 to 59 years, recruited from the Whitehall II epidemiological cohort. Salivary cortisol was sampled on waking, 30 minutes later, and then at 2-hour intervals from 8:00 hours to 22:00 hours. Blood pressure was measured every 20 minutes using ambulatory methods. Effort–reward imbalance and overcommitment to work were assessed with standard questionnaires. Results: Cortisol responses to waking were positively associated with overcommitment in men, with mean increases between waking and 30 minutes of 14.5 and 4.2 nmol/l in high and low overcommitment groups, after adjustment for age, socioeconomic position, smoking, time of waking up, and job demands. Cortisol averaged from 8 samples over the working day was also related to overcommitment in men, with an average difference of 22% between high and lower overcommitment groups. Overcommitment predicted systolic blood pressure over the day in men after adjustment for age, smoking, body mass index, physical activity, and job control, with adjusted means of 132.2 and 125.8 mm Hg in high and low overcommitment groups. There was a significant interaction between overcommitment, socioeconomic position, and time of day in men (p = .016), because systolic pressure was higher in lower status overcommitted men, and rose over the day. Neither effort–reward imbalance nor overcommitment predicted biological responses in women. Conclusions: Chronic neuroendocrine and cardiovascular activation may mediate in part the impact of overcommitment to work on cardiovascular disease risk in men.

Influence of socioeconomic status and job control on plasma fibrinogen responses to acute mental stress.

An elevation in plasma fibrinogen may be one of the pathways through which low socioeconomic status increases cardiovascular disease risk. This study assessed the influence of socioeconomic status, job control, and social isolation on fibrinogen responses to acute stress. The study was conducted with 125 white men and 96 white women aged 47 to 58 years, drawn from the Whitehall II cohort. Socioeconomic status was indexed by grade of employment, with 82 high, 75 intermediate, and 64 low grade participants. Plasma fibrinogen and hematocrit were assessed at baseline, immediately after performance of color-word and mirror tracing tasks, and 45 minutes later. Plasma fibrinogen increased from baseline to stress (from 2.85 +/- 0.57 to 2.92 +/- 0.58 g/liter), remaining elevated 45 minutes after stress (2.89 +/- 0.58 g/liter, p <.001). Fibrinogen concentration was greater in the low than in the high or intermediate employment grade groups, independently of sex, age, body mass index, smoking status, and hematocrit. Fibrinogen responses to acute stress did not differ across employment grades. Women had higher fibrinogen levels than men, but this pattern was abolished in women taking hormone replacement therapy. Men experiencing low job control showed greater fibrinogen responses to acute stress than did those with high job control (p =.003). Fibrinogen levels were greater in socially isolated individuals, but social isolation did not affect responses to acute stress. Socioeconomic status and acute stress had independent effects on the plasma fibrinogen level. Low job control may influence cardiovascular disease risk in men partly through provoking greater fibrinogen stress responses.

Systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure as predictors of cardiovascular disease risk in Men.

We compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) in predicting the risk of cardiovascular disease (CVD), stratifying results at age 60 years, when DBP decreases while SBP continues to increase. We prospectively followed 11 150 male physicians with no history of CVD or antihypertensive treatment through the 2-year questionnaire, after which follow-up began. Reported blood pressure was averaged from both the baseline and 2-year questionnaires. During a median follow-up of 10.8 years, there were 905 cases of incident CVD. For men aged <60 years (n=8743), those in the highest versus lowest quartiles of average SBP (>/=130 versus <116 mm Hg), DBP (>/=81 versus <73 mm Hg), and MAP (>/=97 versus <88 mm Hg) had relative risks (RRs) of CVD of 2.16, 2.23, and 2.52, respectively. Models with average MAP and PP did not add information compared with models with MAP alone (P>0.05). For men aged >/=60 years (n=2407), those in the highest versus lowest quartiles of average SBP (>/=135 versus <120 mm Hg), PP (>/=55 versus <44 mm Hg), and MAP (>/=99 versus <91 mm Hg) had RRs of CVD of 1.69, 1.83, and 1.43, respectively. The addition of other blood pressure measures did not add information compared with average SBP or PP alone (all P>0.05). These data suggest that average SBP, DBP, and MAP strongly predict CVD among younger men, whereas either average SBP or PP predicts CVD among older men. More research should distinguish whether MAP, highly correlated with SBP and DBP, better predicts CVD.

A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women. The Framingham Heart Study.

Sinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein (a). Although prospective data suggest that increased plasma lipoprotein (a) is an independent risk factor for coronary heart disease in men, no prospective studies are available in women. From 1968 through 1975, sinking prebeta lipoprotein was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease. A sinking prebeta lipoprotein band was detectable in 434 of the women (14%) studied. The median follow-up interval was approximately 12 years. Incident cardiovascular disease was associated with band presence using a proportional hazards model that included age, smoking, body mass index, systolic blood pressure, glucose intolerance, low- and high-density lipoprotein cholesterol, and ECG left ventricular hypertrophy. Multivariable adjusted relative risk estimates (with 95% confidence intervals) for outcomes in the band present versus absent groups were as follows: myocardial infarction (82 events), 2.37 (1.48 to 3.81); intermittent claudication (62 events), 1.94 (1.07 to 3.50); cerebrovascular disease (83 events), 1.88 (1.12 to 3.15); total coronary heart disease (174 events), 1.61 (1.13 to 2.29); and total cardiovascular disease (305 events), 1.44 (1.09 to 1.91). A subset analysis indicated that band presence was 50.9% sensitive and 95.4% specific for detecting plasma lipoprotein (a) levels of > 30 mg/dL, the threshold value linked to increased cardiovascular disease risk in men. Sinking prebeta lipoprotein was a valid surrogate for elevated lipoprotein (a) levels in Framingham Heart Study women. Band presence and, equivalently, elevated plasma lipoprotein (a), was a strong, independent predictor of myocardial infarction, intermittent claudication, and cerebrovascular disease. Confirmation of these findings in other longitudinal studies of women is needed.

Hyperinsulinemia, sex, and risk of atherosclerotic cardiovascular disease.

The possibility that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease (CVD) was first suggested 20 years ago. During the last decade, this possibility has received support from three large prospective studies. In the present study, the association between CVD, glucose intolerance, obesity, and hypertension (the GOH conditions) and hyperinsulinemia was examined cross-sectionally in a representative sample (n = 1,263) of the adult Jewish population aged 40-70 years in Israel. Previously known diabetics were excluded. CVD comprising clinical or ECG evidence of ischemic heart disease, as well as clinical evidence of cerebrovascular or peripheral vascular disease, was identified in 97 men and 39 women. A significant (p less than 0.01) hyperinsulinemia-sex interaction was found for CVD rate, with the adjusted risk ratios (followed by 95% confidence limits), relative to the rate in 298 normoinsulinemic women, being 1.15 (0.68-1.95) in 328 normoinsulinemic men, 0.85 (0.48-1.49) in 277 hyperinsulinemic women, and 2.27 (1.33-3.08) in 360 hyperinsulinemic men. Age-adjusted CVD rates in men versus women were: a) similar and low among all normoinsulinemic normotensives and hyperinsulinemics free of any of the GOH conditions (all rates less than or equal to 6.5%); b) similar and high among normoinsulinemic hypertensives (13.4% versus 10.4%); c) significantly higher in men among hyperinsulinemic normotensives with glucose intolerance and/or obesity (15.2% versus 3.3%; p = 0.02) and all hyperinsulinemic hypertensives (21.5% versus 12.8%; p = 0.04). These trends remained significant after adjusting for age, ethnic group, and blood lipids. Therefore, hyperinsulinemia was associated with excess CVD risk in men but not in women, and all excess CVD risk in men was confined to hyperinsulinemic individuals in the presence of glucose intolerance, obesity, or hypertension.