Serum IGF-I and C-reactive protein in healthy black and white young men: The CARDIA male hormone study

ObjectiveAnimal and human studies suggest that C-reactive protein (CRP) may be inversely associated with serum insulin-like growth factor-I (IGF-I) concentrations. However, most human studies have not controlled adequately for confounding factors, particularly nutritional intake. This population-based study examined whether CRP is inversely associated with IGF-I and IGFBP-3 concentrations.MethodsIn cross-sectional analysis, multivariable linear regression with adjustment for age, BMI, smoking status, alcohol intake, and nutritional factors was used to relate log CRP, the independent variable, to IGF-I and IGFBP-3 in a sample of black (n = 364) and white men (n = 486) separately by race.ResultsOnly black men had positive findings: log CRP was significantly associated with IGF-I (β = ?13.1 ng/ml, p = 0.02) and the difference in mean IGF-I concentrations between the highest and lowest quartiles of CRP was 26 ng/ml. There was a statistically significant interaction between log CRP and smoking status (p = 0.02); the regression coefficient for IGF-I predicted from log CRP was significant in smokers (β = ?39.8 ng/ml, p = 0.0001), but not in non-smokers. The difference in mean IGF-I concentrations between highest and lowest quartiles of CRP was 100 ng/ml for black smokers. There were no associations for IGFBP-3.ConclusionsIn our study, CRP levels are inversely associated with IGF-I concentrations in black male smokers; however, the causal nature of the association is unclear and should be studied further.     

早发冠心病患者外周血白细胞端粒长度的变化

目的探讨早发冠状动脉粥样硬化性心脏病(冠心病)患者外周血白细胞端粒长度变化。方法选取2010年1月至2011年11月在青岛市立医院心内科住院的冠心病患者80例,男性43例,女性37例,所有患者为病例组。病例组按照Gensini积分分为4组,A组、B组、C组、D组。病例组按照病变范围分为单支组,双支组和多支组。选取同期经冠状动脉造影或冠状动脉CTA检查排除冠心病的76例查体者为对照组。检测两组生化指标、血压以及端粒相对长度(T/S)。结果病例组外周血白细胞端粒长度T/S比值为0.87±0.31,对照组端粒长度T/S比值为1.12±0.25,病例组外周血白细胞端粒相对长度较对照组明显缩短,差异具有统计学意义(P0.05)。A组、B组、C组和D组患者外周血白细胞端粒长度T/S比值分别为:0.89±0.41,0.91±0.32,0.87±0.29,0.84±0.34,4组比较差异无统计学意义(P均0.05)。单支组、双支组、多支组3组患者外周血白细胞端粒长度T/S比值分别为:0.88±0.35,0.85±0.47,0.89±0.26,3组比较差异无统计学意义(P均0.05)。结论早发冠心病患者外周血白细胞端粒相对长度缩短。早发冠心病外周血白细胞端粒相对长度与冠状动脉的狭窄程度及病变范围无明显相关。     

Aldosterone and telomere length in white blood cells

BACKGROUND: Aldosterone accelerates cardiovascular aging by mechanisms that generate reactive oxygen species. Telomere length in white blood cells (WBCs) may be a bioindicator that registers the accruing burden of systemic oxidative stress. The aim of the present study was, therefore, to examine the relationship between plasma aldosterone and telomere length in WBCs. METHODS: We studied 75 normotensive and never-treated mildly hypertensive men whose blood was drawn for the measurements of plasma aldosterone concentration and the terminal restriction fragment (TRF) length in WBCs. RESULTS: The slope of the TRF-age relationship in the entire cohort showed a decrease in telomere length of 26 +/- 5 base pairs per year (r = -0.46, p <.001). Age-adjusted TRF length was the longest in the lowest aldosterone quartile (6.74 +/- 0.12 kb) and shortest in the highest aldosterone quartile (6.36 +/- 0.11 kb), with intermediate TRF lengths in the second and third aldosterone quartiles (analysis of variance [ANOVA] trend test, p =.025). In telomeric attrition equivalence, participants in the upper aldosterone quartile were 15 years older than their peers in the lowest quartile. CONCLUSIONS: The inverse relationship between aldosterone and WBC telomere length suggests not only that aldosterone is pro-oxidant but that elevated concentrations of this hormone might be linked to a higher rate of telomere attrition and perhaps increased biological aging in humans.     

Alcohol consumption and coronary artery calcium in middle-aged Japanese men

Epidemiologic studies have investigated the relation between alcohol intake and coronary calcification, with controversial results. Furthermore, the influence of heavy drinking has not been well elucidated. In the present study, a random sample of community-based Japanese men aged 40 to 49 years without a history of cardiovascular disease (n=245) were examined for coronary artery calcium (CAC) determined by electron-beam computed tomography and drinking status. There was a J-shaped association between alcohol intake and CAC. There was an increase of CAC in heavy drinkers (>or=46 g/day), and participants who were drinking>or=69 g/day showed a significant increase in CAC compared with never drinkers after adjusting for other cardiovascular risk factors.     

Pulmonary function and cardiovascular risk factor relationships in black and in white young men and women. The CARDIA Study

Pulmonary function is known to be related inversely to incidence of coronary heart disease, congestive heart failure, chronic obstructive lung disease, lung cancer, and death from all causes. Reasons for some of these associations are poorly understood. Relationships between cardiovascular disease risk factors and pulmonary function were examined in 5,115 18- to 30-year-old black and white male and female participants in the study of Coronary Artery Risk Development in Young Adults (CARDIA). Forced expiratory volume in 1 s adjusted for height (FEV1/Ht2) was significantly lower in smokers than nonsmokers and in persons who reported shortness of breath; FEV1/Ht2 was correlated positively with a history of strenuous physical activity, duration of exercise on the treadmill, and high-density lipoprotein cholesterol. It was associated negatively with skinfold thicknesses, serum triglycerides, fasting serum insulin, and the Cook Medley scale of hostility. The association between pulmonary function and heart disease risk may reflect associations with physical fitness, vigor, fatness, and lipid profiles, as well as with cigarette smoking.     

The prevalence and severity of coronary artery calcification on coronary artery computed tomography in black and white subjects

OBJECTIVES: We studied the relationship between coronary artery calcium (CAC) and race in asymptomatic, active-duty personnel in the Prospective Army Coronary Calcium (PACC) project. BACKGROUND: Valid cardiovascular risk assessments in black Americans using coronary artery computed tomography (coronary CT) require the generalizability of population-based CAC score distributions derived from primarily white patient populations. METHODS: Among 1,000 consecutive participants (mean age, 42 +/- 2 years; range, 40 to 45 years), 999 participants underwent coronary CT and indicated a specific racial affiliation. This included white, non-Hispanic in 699 (69.9%) participants and black, non-Hispanic in 194 (19.4%) participants. Univariate associations between race and cardiovascular risk variables were entered into a logistic regression model for CAC that also controlled for socioeconomic status and education. RESULTS: Coronary artery calcium was nearly twice as prevalent in white (19.2%) than in black participants (10.3%) (p = 0.004). Black individuals had a threefold greater prevalence of hypertension, left ventricular hypertrophy, ST-T-wave abnormalities, and current cigarette smoking. Black subjects also had significantly greater blood pressure, high-density lipoprotein cholesterol, glycosylated hemoglobin, lipoprotein(a) and fibrinogen levels, and lower triglyceride levels and waist girth than white subjects. After adjustment for these differences, and socioeconomic adjusters, black individuals were 39% as likely to have any CAC present (odds ratio, 0.39; 95% confidence interval, 0.20 to 0.78; p = 0.007). CONCLUSIONS: Despite a worse cardiovascular risk profile, black Americans have significantly less CAC than white Americans. The use of coronary CT as an accurate risk prediction tool in black Americans will require ethnic-specific data on the presence and severity of CAC.     

Serum androgen levels in black, Hispanic, and white men

CONTEXT: Racial/ethnic differences in androgen levels could account for differences in prostate cancer risk, body composition, and bone loss. OBJECTIVE: The objective of the study was to investigate racial/ethnic variations in testosterone, bioavailable testosterone, dihydrotestosterone (DHT), SHBG, and dehydroepiandrosterone sulfate (DHEAS) levels. DESIGN: The Boston Area Community Health (BACH) Survey was a multistage stratified cluster random sample, recruiting from 2002 to 2005. SETTING: The study was a community-based sample of Boston. PARTICIPANTS: Participants included black, Hispanic, or white individuals, aged 30-79 yr, competent to sign informed consent and literate in English/Spanish. Of 2301 men recruited, 1899 provided blood samples (538 black, 651 Hispanic, 710 white). INTERVENTION: Intervention consisted of data obtained during in-person at-home interview, conducted by a bilingual phlebotomist/interviewer. MAIN OUTCOME MEASURE(S): Testosterone, bioavailable testosterone, DHT, DHT to testosterone ratio, SHBG, and DHEAS were measured. RESULTS: With or without adjustment for covariates, there were no significant differences in testosterone, bioavailable testosterone, or SHBG levels by race/ethnicity. DHEAS levels differed by race/ethnicity before covariate adjustment; after adjustment this difference was attenuated. Before adjustment, DHT and DHT to testosterone ratios did not significantly differ by racial/ethnic group. After adjustment, there was evidence of racial/ethnic differences in DHT (P = 0.047) and DHT to testosterone (P = 0.038) levels. Black men had higher DHT levels and DHT to testosterone ratios than white and Hispanic men. CONCLUSIONS: Because there are no racial/ethnic differences in testosterone levels, normative ranges need not be adjusted by race/ethnicity for androgen deficiency diagnosis for men aged 30-79 yr. Further investigation is needed to determine whether differences in DHT levels and DHT to testosterone ratio can help explain racial/ethnic variations in prostate cancer incidence, body composition, and bone mass.     

Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients

We evaluated the clinical significance of the telomerase activity and telomere length of peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus (SLE). PBMC were isolated from 55 patients with SLE and the telomerase activity was measured by TRAP assay. The telomere length of PBMC was also measured in 30 of these subjects. As a control group, 45 healthy adults with no particular clinical history were studied. The results were compared with clinical data. In patients with active SLE, the telomerase activity of PBMC was significantly increased compared with the control group. In patients with inactive SLE, the PBMC telomerase activity was not different compared with the controls in their 20s, 30s and 40s, but it was significantly increased compared with the controls in their 50s. In SLE patients, the telomerase activity of PBMC was significantly correlated with modified SLEDAI. The telomere length of PBMC in younger SLE patients tended to be shorter than that in the controls, but no difference was observed in older patients. The correlation coefficient between the telomerase activity and telomere length of PBMC in SLE patients was not significant. Abnormalities in the telomerase activity and telomere length observed in SLE patients are considered to be important findings for evaluation of the pathology of SLE.     

Comparison of frequency of coronary artery calcium in healthy Hispanic versus non-Hispanic white men by electron beam computed tomography

We recently demonstrated in subjects referred for the evaluation of cardiovascular disease that coronary atherosclerosis and coronary artery calcium (CAC) were reduced in Hispanics compared with non-Hispanic whites (NHWs). We now evaluate whether this ethnic disparity is present in a unselected healthy cohort of men. Despite the apparently worse risk factor profile, mean and median levels of CAC trended lower in Hispanic men, and the distribution of CAC scores differed from that of NHW (p <0.05), with fewer Hispanic subjects having CAC scores that are generally equated with extensive atherosclerotic burden (>400). These results demonstrate that healthy Hispanic men have reduced CAC compared with age-matched NHW men and this occurs despite evidence for a worse cardiovascular risk profile.     

Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factors.

OBJECTIVES: To compare the significance of a specific feature of coronary atherosclerosis--coronary calcium--in asymptomatic black and white subjects with coronary risk factors. BACKGROUND: The natural history and clinical evolution of coronary atherosclerosis differs between blacks and whites. Differences in the underlying pathobiology of atherosclerosis may be one determinant of the ethnic variability in the clinical manifestation of coronary atherosclerosis. METHODS: In 1,375 high-risk but asymptomatic subjects (93 blacks [6.8%] and 1,282 whites [93.2%]) with at least one risk factor but no prior evidence of coronary disease, we assessed coronary risk factors, calculated Framingham risk of a coronary event and evaluated coronary calcium with digital subtraction fluoroscopy. We then followed these subjects clinically for 70 +/- 13 months, noting the occurrence of the following coronary events: death due to coronary heart disease (CHD); myocardial infarction (MI); angina pectoris; and performance of coronary bypass or angioplasty. RESULTS: Risk factor profiles were similar in black and white subjects (6-year Framingham risk 15 +/- 7% in blacks, 14 +/- 8% in whites [NS]). Coronary calcium was present in 59.9% of white subjects but only 35.5% of black subjects (p = 0.0001). Nevertheless, after 70 months of follow-up, more blacks than whites (22 blacks [23.7%] vs. 190 whites [14.8%]; p = 0.04) suffered one of the following end points: CHD death, MI, angina or revascularization. The age, gender and coronary risk-adjusted odds ratio of black race for at least one event was 2.16 (95% CI 1.34 to 3.48). CONCLUSIONS: Despite having a lowered prevalence of coronary calcium than high risk whites, high risk blacks suffer more CHD events. Coronary calcium therefore does not carry the same pathobiologic significance in blacks that it does in whites, consistent with the concept that there are specific racial differences in the natural history of CHD and its evolution into clinically manifest events.     

Metabolic syndrome is associated with coronary artery calcium in asymptomatic white Brazilian men considered low-risk by Framingham risk score

The authors investigated whether the metabolic syndrome is associated with coronary artery calcium (CAC) independently of 10-year coronary heart disease risk assessment by Framingham risk scores (FRS) in asymptomatic white Brazilian men. In a group of 458 men (mean age 46+/-7 years), the 10-year coronary heart disease risk was 9%+/-8%, and the metabolic syndrome and CAC were present in 24% and 41% of the participants, respectively. Compared with those classified as low risk (<10% FRS; n=256), men with FRS of 10% or more had an odds ratio of 4.57 (95% confidence interval, 3.08-6.82; P<.0001) for the presence of any CAC. The prevalence of CAC increased monotonically with the increasing number of metabolic syndrome components (none=29%, 1 or 2=44%, and >or=3=51%, P=.002 for trend). The presence of the metabolic syndrome was associated with an increased risk of CAC: odds ratio, 1.94 (95% CI, 1.05-3.61); however, this finding was significant only in those individuals classified as low risk (FRS <10%). In conclusion, metabolic syndrome is associated with subclinical atherosclerosis in Brazilian participants considered at low risk according to FRS.     

Telomerase and telomere length in multiple myeloma: correlations with disease heterogeneity,cytogenetic status,and overall survival

We have investigated the significance of telomerase activity (TA) and telomere length (TL) in multiple myeloma (MM). The analyses were undertaken on CD138+ MM cells isolated from the marrow of 183 patients either at diagnosis or in relapse. There was heterogeneity in telomerase expression; 36% of the patients had TA levels comparable to those detected in normal plasma cells, and 13% of patients had levels 1- to 4-fold greater than in a neuroblastoma cell line control. The TL of MM cells was significantly shorter than that of the patients' own leukocytes; in 25% of patients, the TL measured less than 4.0 kbp. Analysis of TL distribution indicated selective TA-mediated stabilization of shorter telomeres when mean TL fell below 5.5 kbp. Unusually long (10.8-15.0 kbp) telomeres were observed in 7 patients, and low TA was observed in 5 of 7 patients, suggesting the operation of a TA-independent pathway of telomere stabilization. A strong negative correlation existed between TA and TL or platelet count. TL negatively correlated with age and with interleukin-6 (IL-6) and beta2-microglobulin levels. Various cytogenetic abnormalities, including those associated with poor prognosis, strongly correlated with TA and, to a lesser extent, with short TL. High TA and short TL defined a subgroup of patients with poor prognosis. At 1 year the survival rate in patients with TA levels lower than 25% of neuroblastoma control and TL greater than 5.5 kbp was 82%, whereas in patients with higher TA and shorter TL the survival rate was 63% (P =.004). The 2-year survival rate for patients with TA levels lower than 25% was 81%, and it was 52% in those with higher TA levels (P <.0001).     

Telomerase activity and telomere length in acute leukemia: correlations with disease progression,subtypes and overall survival

The progressive shortening of telomeres and the activation of telomerase are considered to be one of the important mechanisms in cellular immortalization and disease progression. Bone marrow samples were collected from 148 patients with acute leukemia (AL). Based on the stage of the disease, patients were divided into the newly diagnosed group, the relapsed group and the complete remission (CR) group. telomerase activity (TA) was examined by PCR-ELISA, and telomere length (TL) was examined by Southern blot analyses. TA and TL were analyzed in relation to AL stage and subtype. Five-year survival was analyzed using Kaplan–Meier survival curve. TA in AL patients was higher than healthy individuals. TA level was the highest in the relapsed group, followed by the newly diagnosed group, and then the CR group. TA had no difference between acute nonlymphocytic leukemia (ANLL) group and acute lymphocytic leukemia (ALL) group. But TA in group of subtype M3 was lower than other subtypes of ANLL. TL in AL group was shorter than the control group. TL was the shortest in the relapsed group, followed by the newly diagnosed group, and finally the CR group. TL exhibited an inverse correlation with TA. The group of patients with high TA had a significantly poorer five-year-survival than that of low TA group. TA is elevated and TL is shortened in AL patients. There is a significant inverse correlation between TL and TA. Patients in late-stage disease had shorter TL and higher TA than those in early stages. The shortened TL and elevated TA correlated with disease progression and relapse, and they may serve as prognostic factors for AL patients with poor outcome. M3 subtype is special with relative lower TA and long-lasting survival than other subtypes.     

Severity of coronary artery disease in black and white male veterans and likelihood of revascularization

BACKGROUND: Many reports in the literature have found the use of invasive cardiac procedures in black patients to be less common than in white patients. These reports tend to have small numbers of black patients compared with white patients or rely on the information contained in claims or administrative data. METHODS AND RESULTS: Cardiac catheterization reports were reviewed in a Veterans Administration hospital that serves a large number of black patients. After review of the medical histories and hemodynamic and angiographic findings in 726 black and 734 white male veterans, data were collected to determine recommended and actual therapy. Death was assessed after a 4- to 10-year follow-up period. White patients were more likely to have significant coronary artery lesions than black patients. Multivariate analysis showed that the likelihood of patients actually having percutaneous transluminal coronary angioplasty or coronary artery bypass surgery did not differ by ethnicity when controlling for disease extent or severity. Coronary artery bypass surgery was associated with decreased mortality rates for both black and white patients. Although short-term death in blacks was not different from whites, blacks had an increased long-term risk for death. CONCLUSIONS: After coronary angiography, black veterans and white veterans appear to undergo revascularization procedures related to the severity of disease. The decreased long-term life expectancy of black men as compared with whites is not necessarily explained by the presence of or treatment for coronary artery disease in this population.     

The impact of weight change on cardiovascular disease risk factors in young black and white adults: the CARDIA study

OBJECTIVE: To quantify the relation between weight change and change in blood pressure, lipids and insulin levels, and determine if this relation differs by race or initial level of obesity.DESIGN: Longitudinal cohort study.SETTING AND PARTICIPANTS: Community-based sample of 3325 black and white men and women aged 18-30 y from four centers followed for 10 y. Women pregnant at baseline or 10th year exam and persons without a recorded weight at both exams were excluded. Participants whose baseline BMI was >or=25 kg/m(2) were classified as overweight. Height, weight, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), fasting triglycerides, fasting insulin, and blood pressure were measured at baseline and Year 10.RESULTS: The mean (s.d.) of weight gained over 10 y was 10.5 (10.0) kg (black men), 11.7 (11.0) (black women), 7.7 (8.0) (white men), and 7.2 (10.0) (white women). An increase in weight was associated with adverse changes in all factors in all race-sex groups. For example, a 9.1 kg (20-lb) weight increase in persons not overweight at baseline predicted an increase in LDL-C ranging from 0.23 mmol/l in black women to 0.28 mmol/l in black men and a decrease in HDL-C from 0.09 mmol/l (white women) to 0.11 mmol/l (white men) (all P<0.0001). The estimated change in triglycerides was greater in white than in black participants (P<0.02); no other racial differences were found. Changes in triglycerides (P<0.00001) and fasting insulin (P=0.004) were greater in men than in women. Only for LDL-C was a weight change-associated increase significantly different (greater, P<0.001) for nonoverweight persons than for those overweight at baseline. None of these associations were highly specific. Mean levels of LDL-C, HDL-C, and systolic blood pressure improved among all those who lost or did not gain weight.CONCLUSIONS: A 10 y weight gain in young adults of both races and sexes tends to confer adverse changes in their levels of LDL-C, HDL-C, triglycerides, fasting insulin, and blood pressure. This effect occurs regardless of initial weight, age, race, or gender.     

Prediction of coronary artery calcium in young adults using the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score: the CARDIA study

BACKGROUND: Using data from autopsied young people aged 15 to 34 years, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study developed a risk score based on age, sex, smoking status, high-density lipoprotein and non-high-density lipoprotein cholesterol levels, and the presence of obesity, hyperglycemia, and hypertension to predict advanced coronary artery atherosclerosis. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study assessed coronary artery calcium (CAC) by computed tomography in young adults participating in the 15-year examination. The PDAY risk score was calculated from risk factors measured at the CARDIA examinations at years 0, 5, 10, and 15. RESULTS: Odds ratios for amount of CAC (6 ordinal categories) for a 1-point increase in risk score computed from the modifiable risk factors ranged from 1.10 to 1.16 (all statistically significant). Odds ratios for presence of any amount of CAC ranged from 1.09 to 1.15 (all statistically significant), with the highest odds ratio for the risk score at year 0. An increase in risk score between years 0 and 15 increased the odds of CAC, and a decrease in risk score decreased the odds of CAC. A positive family history of cardiovascular disease increased the odds of CAC. The c statistics ranged from 0.752 to 0.770, with the highest discrimination based on the year 0 revised PDAY risk score that included family history and increased the points for the sex differential. CONCLUSION: The PDAY risk score predicts CAC up to 15 years before its assessment, and risk score change during 15 years affects the risk of CAC.     

Heart rate-corrected QT interval prolongation predicts risk of coronary heart disease in black and white middle-aged men and women: the ARIC study

OBJECTIVES: We aimed to study the predictive value of heart rate-corrected QT interval (QTc) for incident coronary heart disease (CHD) and cardiovascular disease (CVD) mortality in the black and white general population, and to validate various QT measurements. BACKGROUND: QTc prolongation is associated with higher risk of mortality in cardiac patients and in the general population. Little is known about the association with incident CHD. No previous studies included black populations. METHODS: We studied the predictive value of QTc prolongation in a prospective population study of 14,548 black and white men and women, age 45 to 64 year. QT was determined by the NOVACODE program in the digital electrocardiogram recorded at baseline. RESULTS: In quintiles of QTc, cardiovascular risk profile deteriorated with longer QTc, and risk of CHD and CVD mortality increased. The high risk in the upper quintile was mostly explained by the 10% with the longest QTc. The age-, gender-, and race-adjusted hazard ratios for CVD mortality and CHD in subjects with the longest 10% relative to the other 90% of the gender-specific QTc distribution were 5.13 (95% confidence interval 3.80 to 6.94) and 2.14 (95% confidence interval 1.71 to 2.69), respectively. The increased risk was partly, but not completely, attributable to other risk factors or the presence of chronic disease. The association was stronger in black than in white subjects. Manual- and machine-coded QT intervals were highly correlated, and the method of rate correction did not affect the observed associations. CONCLUSIONS: Long QTc is associated with increased risk of CHD and CVD mortality in black and white healthy men and women.