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1.
J Acquir Immune Defic Syndr ; 28(4): 332-5, 2001 Dec 01.
Article in English | MEDLINE | ID: mdl-11707668

ABSTRACT

BACKGROUND: In a previously reported study, 21 women (propositi) who reported changes in body habitus during highly active antiretroviral therapy (HAART) were evaluated and compared with 21 women (comparison group) on HAART who did not report body habitus changes. Mean durations of HAART at baseline evaluation were 12.5 and 15.2 months for the propositi and comparison group, respectively. OBJECTIVE: Follow-up of the propositi and comparison group was conducted to determine whether body habitus changes and lipid abnormalities are progressive, stable, or improved with time and alteration of the HAART regimen. METHODS: Patients were evaluated by standardized interview, physical examination, body weight, body mass index, CD4 cell count, plasma HIV RNA levels, and lipid profiles. RESULTS: Fourteen of 21 propositi were available for follow-up. The mean duration of HAART was 42.7 months; body habitus changes were stable in 10 of the 14 women. Thirteen of 21 women in the comparison group were available for follow-up after a mean duration of HAART of 38.5 months; 2 of the 13 women had developed body habitus changes at follow-up. In both groups, mean serum lipid values at follow-up remained elevated to levels associated with increased cardiovascular risk. CONCLUSIONS: Body habitus changes in women most often developed within 1 year of initiation of HAART. Changes were largely stable after 2.5 additional years of HAART. Only modest and inconsistent improvement was achieved with alteration in the HAART regimen. Serum lipid abnormalities evident within the first year of HAART were also stable with 2.5 additional years of therapy.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Seropositivity/drug therapy , Lipids/blood , Adult , Antiretroviral Therapy, Highly Active , Body Mass Index , Body Weight , Female , Follow-Up Studies , HIV Infections/blood , HIV Infections/pathology , HIV Seropositivity/blood , HIV Seropositivity/pathology , Humans
2.
Hum Biol ; 73(1): 91-104, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11332648

ABSTRACT

Elevated plasma lipoprotein(a) [Lp(a)] level has been established as an independent risk factor for atherosclerosis and coronary heart disease. Considerable ethnic group differences in the distribution of plasma Lp(a) levels have raised public health concerns. Recently, we have reported that Samoans have the lowest plasma Lp(a) levels of any population group. In the present investigation, we report the contribution of two apolipoprotein(a) (APOA) polymorphisms, the kringle 4 type 2 (K4) repeat and the pentanucleotide repeat (PNR), in affecting plasma Lp(a) levels in an American Samoan sample (n = 309). The K4 repeats ranged in size from 15 to 40. The common alleles contained repeats ranging from 26 to 36 with allele frequencies between 5.5% to 9.7%, and these accounted for 82% of all alleles. An inverse relationship between K4 repeat number and plasma Lp(a) level was observed for single-banded (r = -0.59, p = 0.0001) and double-banded phenotypes (r = -0.50, p = 0.0001). This polymorphism explained 60% of the variation in plasma Lp(a) level in American Samoans. For the PNR polymorphism, five different repeat alleles and eight different genotypes were identified; the most common allele was eight repeats. The *8 PNR allele was associated with a wide range of K4 repeats, the *9 PNR allele with larger K4 repeats (25-40), and the *10 PNR with smaller K4 repeats (15-24). Analysis of variance (ANOVA) revealed that the PNR polymorphism accounts for 2.1% of the variability in plasma Lp(a) levels in this sample, when the K4 repeat polymorphism was taken into account. Our data show that common polymorphisms in the APOA gene are major determinants of plasma Lp(a) variation in American Samoans.


Subject(s)
Apolipoproteins A/genetics , Lipoprotein(a)/blood , Polymorphism, Genetic , Tandem Repeat Sequences , Adult , American Samoa , Analysis of Variance , Cross-Sectional Studies , Humans , Middle Aged
3.
Hum Biol ; 72(2): 321-36, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10803663

ABSTRACT

Plasma lipoprotein(a) [Lp(a)]-consisting of a disulfide-linked complex of apolipoprotein B and apolipoprotein (a)--levels are considered to be an independent risk factor for coronary heart disease. There are considerable ethnic group differences in the distribution of plasma Lp(a) levels that raise public health concerns. Although plasma Lp(a) distribution has been determined in various ethnic groups, no such information is available in Pacific Islanders. In this study we have determined the distribution and correlates of plasma Lp(a) in population-based samples of 361 American Samoans (145 men, 216 women) and 560 Western Samoans (265 men, 295 women), aged 20-70 years. Plasma Lp(a) levels were measured using a commercial enzyme-linked immunosorbent assay. The distribution of plasma Lp(a) levels in both groups was highly skewed with 73% and 65% of values in the 0-5 mg/dl range in American Samoans and Western Samoans, respectively. The mean (6.4 mg/dl) and median (2.2 mg/dl) Lp(a) levels in pooled Samoans were significantly lower when compared with other ethnic groups using the same measurement kit. Plasma Lp(a) correlated significantly with total and LDL cholesterol in both genders after correcting for the contribution of Lp(a) cholesterol, and with apolipoprotein B in women after the correction for Lp(a)-apoB, but not with age, smoking, alcohol intake, or body mass index. Our data show that Samoans, Polynesians of Pacific Islands, have strikingly lower Lp(a) levels than all other reported population groups. These data are consistent with the hypothesis that genetic factors account for interethnic group variation in plasma Lp(a) levels.


Subject(s)
Lipoprotein(a)/blood , White People , Adult , Age Distribution , American Samoa , Anthropometry , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cohort Studies , Cross-Sectional Studies , Female , Humans , Independent State of Samoa , Longitudinal Studies , Male , Middle Aged , Probability , Radioimmunoassay , Reference Values , Sex Distribution
4.
Arterioscler Thromb Vasc Biol ; 19(9): 2241-4, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10479668

ABSTRACT

Serum creatinine, a surrogate for both renal function and homocysteine generation, is a determinant of fasting plasma total homocysteine levels in coronary artery disease (CAD) patients. We hypothesized that among stable-CAD patients with normal creatinine levels (ie, 0.2). Consistent with the impact of folic acid fortification of cereal grain flour in the general population, only 1 of the CAD subjects (0.6%) had a plasma folate level <3 ng/mL. We conclude that serum cystatin C levels may reflect subtle decreases in renal function that independently predict fasting total homocysteine levels among stable-CAD patients with normal serum creatinine.


Subject(s)
Coronary Disease/blood , Creatinine/blood , Cystatins/blood , Fasting/blood , Homocysteine/blood , Adult , Aged , Coronary Disease/physiopathology , Cystatin C , Female , Humans , Kidney/physiopathology , Male , Middle Aged , Predictive Value of Tests , Reference Values
5.
Health Psychol ; 18(3): 241-50, 1999 May.
Article in English | MEDLINE | ID: mdl-10357505

ABSTRACT

Lipids increase during psychological stress, but no studies have compared the effects of acute and chronic stressors on lipid responsivity in the same individuals. One hundred middle-aged men (n = 92) and women (n = 8) were examined during high chronic occupational stress, low chronic stress, and acute laboratory stressors. In addition to measures of perceived stress and affect, an extensive battery of lipid and lipoprotein measures was undertaken at each time point. Most lipid parameters were significantly increased during the chronic and acute stressors, although the responses to the different stressors were not consistently associated. For example, significant correlations among the chronic and acute stress responses were apparent for the apoproteins, but not for total, low density lipoprotein, or high density lipoprotein cholesterol. The factors and processes regulating these variables during stress may be different during acute and chronic stressors.


Subject(s)
Aviation , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Occupational Diseases/blood , Occupational Diseases/psychology , Stress, Psychological/blood , Stress, Psychological/psychology , Acute Disease , Adult , Chronic Disease , Female , Humans , Male , Middle Aged
6.
Health Psychol ; 18(3): 251-61, 1999 May.
Article in English | MEDLINE | ID: mdl-10357506

ABSTRACT

This study examined behavioral and physiological influences on lipid concentrations during acute and chronic stressors. One hundred men (n = 92) and women (n = 8) were tested during a chronic stressor and during 2 acute stressors. During chronic stress, diet, physical activity, exercise, and sleep were examined. During the acute stressors, catecholamines, cortisol, plasma volume, and cardiovascular responses were examined. None of the behavioral influences could explain the lipid response to chronic stress. Responses of the atherogenic lipids to acute stressors were not solely reflecting hemoconcentration of the plasma but were moderately correlated with cardiovascular, epinephrine, and cortisol reactivity. Diastolic blood pressure reactors to the acute stressors had larger lipid responses to the chronic stressor than did nonreactors. Elevations in blood lipids during stress are not artifacts and may be clinically significant.


Subject(s)
Blood Pressure/physiology , Cholesterol/blood , Epinephrine/blood , Heart Rate/physiology , Hydrocortisone/blood , Stress, Psychological/blood , Stress, Psychological/psychology , Acute Disease , Chronic Disease , Electrocardiography , Energy Intake , Exercise , Female , Humans , Male , Sleep/physiology
7.
J Acquir Immune Defic Syndr ; 21(2): 107-13, 1999 Jun 01.
Article in English | MEDLINE | ID: mdl-10360801

ABSTRACT

Twenty-one women (propositi) who expressed serious concerns about changes in body habitus during highly active antiretroviral therapy (HAART) were evaluated by thorough physical examination, anthropometric measurements, and serum lipid and endocrine assays. The same evaluations were carried out in a comparison group of 21 women who received HAART but did not complain of changes in habitus. No significant demographic differences were found between the propositi and the comparison group, nor were there significant differences in CD4 count or plasma viral load (PVL) between the two groups. Lipid analyses were also performed on plasma obtained prior to HAART from 12 of the women. The frequency of changes reported by the 21 propositi were increase in abdominal size (90%), increase in breast size (71%), weight gain of >5 kg (43%), peripheral fat wasting (43%), buttock fat wasting (38%) and development of cervicodorsal fat pad (19%). A subset of patients in the comparison group experienced increase in abdominal size (29%) and weight gain >5 kg (19%), but none experienced clinically detectable peripheral or buttock fat wasting, increased breast size, or development of cervicodorsal fat pads. Mean waist circumference, waist-to-hip ratios (WHR), body fat, and body mass index (BMI) were above the desirable range for women in both propositi and the comparison group. Levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol associated with increased cardiovascular risk were found in 48%, 62%, 45%, and 33%. respectively, of the propositi, with similar findings in the comparison group. Fasting insulin levels were elevated in 4 propositi and 6 of the comparison group; mean insulin levels were within the normal range for both groups. In the comparison of lipids for the subset of patients before and after HAART therapy, HAART was associated with significant increases in total cholesterol, apolipoprotein B, and HDL cholesterol. Changes in body habitus caused by redistribution of fat occur commonly in women receiving HAART. Serum lipid abnormalities also are common during HAART and appear to be as frequent in women who do not experience clinically apparent body fat redistribution as in those who do. The observed changes in body fat distribution and in serum lipid levels are alterations that have been strongly correlated with increased risk for cardiovascular disease. Therefore, an understanding of the basis of these phenomena, and the risks with which they may be associated in this population, will be important for therapeutic decision making in women with HIV disease.


Subject(s)
Adipose Tissue/drug effects , Anti-HIV Agents/adverse effects , Body Constitution , HIV Infections/drug therapy , Lipids/blood , Adult , Anti-HIV Agents/therapeutic use , Body Mass Index , Cardiovascular Diseases/etiology , Cholesterol/blood , Cohort Studies , Drug Therapy, Combination , Female , HIV Infections/blood , HIV Infections/metabolism , HIV Infections/pathology , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/therapeutic use , Humans , Insulin/blood , Middle Aged , Time Factors , Triglycerides/blood , Weight Gain/drug effects
8.
J Am Soc Nephrol ; 10(5): 1095-9, 1999 May.
Article in English | MEDLINE | ID: mdl-10232697

ABSTRACT

Mild hyperhomocysteinemia, a putative risk factor for atherothrombotic cardiovascular disease morbidity and mortality, may contribute to the excess incidence of atherothrombotic outcomes in the dialysis-dependent end-stage renal disease population. Hemodialysis access (fistula or graft) thrombosis is an unfortunately common and costly morbidity in this patient population. In this study, using a prospective design, the potential relationship between baseline nonfasting, predialysis plasma total homocysteine (tHcy) levels and vascular access-related morbidity was examined in a cohort of 84 hemodialysis patients with a fistula or prosthetic graft as their primary hemodialysis access. Vascular access thrombotic episodes were recorded over a subsequent 18-mo follow-up period. Forty-seven patients (56% of the total) had at least one access thrombosis during the 18-mo follow-up period (median follow-up, 13 mo; rate, 0.6 events per patient-year of follow-up). Proportional hazards modeling revealed that each 1 microM/L increase in the tHcy level was associated with a 4.0% increase in the risk of access thrombosis (95% confidence interval, 1.0 to 6.0%, P = 0.008). This association persisted after adjustment for type of access (fistula versus graft), age, gender, time on dialysis, diabetes, smoking, hypertension, nutritional status, urea reduction ratio, dyslipidemia, and the presence of previous vascular disease. Elevated tHcy levels appear to confer a graded, independent increased risk for hemodialysis access thrombosis. A randomized, controlled trial examining the effect of tHcy-lowering intervention on hemodialysis access thrombosis appears to be justified.


Subject(s)
Catheters, Indwelling/adverse effects , Homocysteine/blood , Renal Dialysis , Thrombosis/etiology , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk Factors , Thrombosis/epidemiology
9.
JAMA ; 281(13): 1189-96, 1999 Apr 07.
Article in English | MEDLINE | ID: mdl-10199428

ABSTRACT

CONTEXT: Although evidence suggests that homocysteine is a risk factor for cardiovascular disease in adults, little information exists on homocysteine levels in children. OBJECTIVES: To describe the distribution of serum homocysteine concentrations among children and to examine the association between homocysteine levels and several characteristics, including serum levels of folic acid and vitamins B12 and B6. DESIGN: Cross-sectional analysis. SETTING: School-based cohort from California, Louisiana, Minnesota, and Texas. PARTICIPANTS: A total of 3524 US schoolchildren, aged 13 and 14 years, from the Child and Adolescent Trial for Cardiovascular Health (completed in 1994). Measurement was conducted in 1997. MAIN OUTCOME MEASURE: Nonfasting serum total homocysteine concentration. RESULTS: The distribution of homocysteine values ranged from 0.1 to 25.7 micromol/L (median, 4.9 micromol/L). Geometric mean homocysteine concentration was significantly higher in boys (5.22 micromol/L) than girls (4.84 micromol/L); blacks (5.51 micromol/L) than whites (4.96 micromol/L) or Hispanics (4.93 micromol/L); nonusers of multivitamins (5.09 micromol/L) than users (4.82 micromol/L); and smokers (5.19 micromol/L) than nonsmokers (5.00 micromol/ L). Serum homocysteine was significantly inversely correlated with serum levels of folic acid (r= -0.36; P = .001), vitamin B12 (r = -0.21; P = .001), and vitamin B6 (r = -0.18; P = .001). Serum homocysteine was not significantly associated with serum lipid levels or family history of cardiovascular disease and was only weakly related to body mass index and systolic blood pressure. After multivariate adjustment, homocysteine remained independently associated with sex, race, serum folic acid and vitamin B12 levels, and systolic blood pressure. CONCLUSIONS: The distribution of homocysteine levels in children is substantially lower than that observed for adults; however, a small percentage of children are still potentially at elevated risk for future cardiovascular disease. Serum folic acid may be an important determinant of homocysteine levels in children.


Subject(s)
Cardiovascular Diseases/epidemiology , Homocysteine/blood , Adolescent , Cross-Sectional Studies , Female , Folic Acid/blood , Health Surveys , Humans , Male , Pyridoxine/blood , Reference Values , Regression Analysis , Risk Factors , Vitamin B 12/blood
10.
J Am Soc Nephrol ; 10(1): 164-6, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9890323

ABSTRACT

Serum creatinine, a surrogate for both renal function and homocysteine generation, is an important determinant of fasting plasma total homocysteine levels in stable renal transplant recipients. In this study, it is hypothesized that among stable renal transplant recipients with normal creatinine levels (i.e., < or = 1.5 mg/dl), serum cystatin C, a more sensitive indicator of GFR, would better predict fasting total homocysteine levels compared with serum creatinine. Fasting plasma total homocysteine, folate, vitamin B12, and pyridoxal 5'-phosphate levels, along with serum cystatin C, creatinine, and albumin levels, were determined in 28 consecutive renal transplant recipients (mean age 47 +/- 14 yr; 60.7% men) with stable allograft function, whose serum creatinine was < or = 1.5 mg/dl. General linear modeling with analysis of covariance revealed that serum cystatin C was independently predictive (partial R = 0.494; P = 0.023) of fasting total homocysteine levels after adjustment for age, gender, vitamin status, albumin, and creatinine levels. In contrast, creatinine levels were not predictive of fasting total homocysteine levels in this model (P = 0.110) or an identical model that excluded cystatin C (P = 0.131). Serum cystatin C levels may reflect subtle decreases in renal function that independently predict fasting total homocysteine levels among stable renal transplant recipients with a normal serum creatinine.


Subject(s)
Cystatins/blood , Fasting/blood , Homocysteine/blood , Kidney Transplantation , Adult , Aged , Creatinine/blood , Cystatin C , Female , Humans , Male , Middle Aged , Statistics as Topic
11.
Atherosclerosis ; 137(1): 215-21, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9568755

ABSTRACT

Low concentrations of high-density lipoprotein cholesterol (HDL-C) are a recognized risk factor for atherosclerotic cardiovascular disease. Exercise is often recommended to increase HDL-C, but the effect of exercise training on HDL levels and metabolism in subjects with low HDL concentrations is not well defined. The present study compared the HDL response to 12 months of supervised endurance exercise training without weight loss in 17 men aged 26 49 years with initially low ( < 40 mg/dl, N=7) or normal ( > 44 mg/dl, N=10) HDL-C levels. HDL-C levels and HDL apolipoprotein metabolism were assessed while the subjects consumed controlled diets before and after the year of training. Increases in total (5.1+/-2.8 versus 1.9+/-4.2 mg/dl, P=0.08) and HDL2 (3.8+/-2.9 versus 0.4+/-1.1 mg/dl, P=0.01) cholesterol were greater in men with normal initial HDL-C levels. Catabolic rates for HDL apolipoproteins decreased 7-14% and biological half-lives increased 10-15% after exercise training in subjects with normal HDL, but were unchanged in the low HDL-C group. HDL apolipoprotein synthetic rates were not consistently affected by exercise training in either group. Postheparin lipoprotein lipase activity increased 27%, the clearance rate of intravenous triglycerides increased 14%, and apolipoprotein B levels decreased 16% with training in subjects with normal HDL-C but were unchanged in the low HDL-C group. We conclude that the ability to increase HDL-C levels through endurance exercise training is limited in subjects with low initial HDL-C, possibly because exercise training in such subjects fails to alter triglyceride metabolism.


Subject(s)
Cholesterol, HDL/blood , Exercise/physiology , Adult , Apolipoproteins/blood , Cholesterol, LDL/blood , Fat Emulsions, Intravenous/pharmacokinetics , Humans , Lipase/metabolism , Lipoprotein Lipase/metabolism , Male , Metabolic Clearance Rate , Middle Aged , Triglycerides/blood
12.
Ann Epidemiol ; 8(2): 84-91, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9491932

ABSTRACT

PURPOSE: Although public health interventions have not specifically targeted high density lipoprotein (HDL) cholesterol, observed changes in the prevalence of other cardiovascular risk factors would be expected to have differential effects on HDL. This study examined secular trends in HDL in relation to changes in other cardiovascular risk factors for the years 1981 through 1993 in the Pawtucket Heart Health Program (PHHP) study communities. METHODS: Nonfasting HDL levels were assessed in 12,223 respondents to six biennial population random sample surveys. RESULTS: Between 1981 and 1993, mean HDL cholesterol declined by 0.08 mmol/L in both men and women after adjustment for age, city, education, hormone use, medications, recent alcohol use, smoking, regular exercise, body mass index (BMI), and total cholesterol, (p for trend < 0.001). There was no apparent laboratory explanation for the trend which occurred concurrent with decreased smoking prevalence, increasing BMI and decreased prevalence of recent alcohol use. Decreasing HDL cholesterol was observed consistently across subgroups defined by smoking, alcohol use and BMI. CONCLUSIONS: Although several favorable cardiovascular risk factor trends have been observed in recent decades, declining HDL cholesterol is also of interest, particularly in conjunction with population increases in BMI.


Subject(s)
Cholesterol, HDL/blood , Adult , Analysis of Variance , Body Mass Index , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cross-Sectional Studies , Female , Humans , Male , Rhode Island/epidemiology , Risk Factors
13.
Metabolism ; 46(9): 992-6, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9284885

ABSTRACT

We have identified a kindred in Providence, RI, deficient in hepatic triglyceride lipase (HL). The two affected brothers have coronary heart disease and elevated levels of triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein [apo] A-I. The lipoprotein lipase (LPL) activity is normal. We and others have postulated that the effects of oral anabolic steroids on HDL metabolism are mediated by HL. To test this hypothesis, we treated these two men and two controls with the oral androgen stanozolol (6 mg/d) for 2 weeks. Consistent with other reports, HL activity increased a mean of 277% in controls with a concomitant decrease in HDL cholesterol (49%), HDL2 cholesterol (90%), HDL3 cholesterol (16%), and apo A-I (41%) and no change in apo A-II. Although stanozolol failed to induce HL activity in the HL-deficient man, HDL cholesterol, HDL2 cholesterol, and apo A-I were reduced a mean of 20%, 48%, and 32%, respectively. In contrast to controls, HDL3 cholesterol (46%) and apo A-II (14%) increased in HL-deficient subjects. Stanozolol treatment also increased LPL activity (124% +/- 86%, n = 4) and decreased lipoprotein(a) ([Lp(a)] 66% +/- 3%, n = 3) in the three men with detectable levels. The data indicate that in addition to stimulation of HL activity, stanozolol treatment changes HDL cholesterol concentration and subfraction distribution by other mechanisms.


Subject(s)
Anabolic Agents/therapeutic use , Lipase/deficiency , Lipoproteins/blood , Liver/enzymology , Stanozolol/therapeutic use , Aged , Anabolic Agents/administration & dosage , Apolipoproteins/blood , Enzymes/blood , Humans , Lipids/blood , Lipolysis , Liver/drug effects , Liver/physiopathology , Male , Stanozolol/administration & dosage , Time Factors
14.
Psychophysiology ; 34(3): 285-91, 1997 May.
Article in English | MEDLINE | ID: mdl-9175443

ABSTRACT

The purpose of this study was to establish the temporal stability of lipid responses to acute psychological stress. Eighteen men were tested twice an average of 16.2 months apart in identical laboratory reactivity protocols. Total cholesterol, triglycerides, high- and low-density lipoprotein-cholesterol, plasma volume, heart rate, and blood pressure were assessed during rest, serial subtraction, and speech. After correction for changes in plasma volume, significant elevations were recorded for all variables during the speech task, but fewer variables showed changes during the serial subtraction task. Strong intersession associations were found when considering levels of the variables during baseline and stress (rs > or = .58). Correlations for the change scores ranged from .36 to .52 for the atherogenic lipids and from .39 to .87 for the cardiovascular variables. Little evidence was found for stability of plasma volume changes. There is moderate to high temporal stability of the atherogenic lipids when considering rest and stress levels and small to moderate temporal stability when considering change scores.


Subject(s)
Lipid Metabolism , Stress, Psychological/metabolism , Adult , Blood Pressure/physiology , Heart Rate/physiology , Humans , Male , Middle Aged , Neuropsychological Tests , Stress, Psychological/psychology , Task Performance and Analysis
15.
Atherosclerosis ; 130(1-2): 199-202, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9126665

ABSTRACT

Elevated total homocysteine (tHcy) levels are associated with increased risk for atherosclerotic cardiovascular disease. tHcy levels are higher in men than in women, and estrogen replacement therapy may reduce tHcy levels in postmenopausal women. The effect of androgenic hormones on tHcy levels in men has not been examined. The present study determined the effect of supraphysiologic doses of testosterone, with or without its aromatization to estradiol, on fasting tHcy levels in 14 normal male weightlifters aged 19-42 years. Subjects received testosterone-enanthate (200 mg/week intramuscularly), the aromatase inhibitor, testolactone (1 g/day orally), or both drugs together in a crossover design. Each treatment lasted 3 weeks and each treatment was separated by a 4-week washout. Both testosterone regimens increased serum testosterone levels, whereas estradiol increased only during testosterone alone. Mean tHcy levels were not significantly altered when testosterone was given alone or together with testolactone. Testolactone did not significantly influence tHcy levels. We conclude that short-term, high-dose testosterone administration does not affect fasting tHcy levels in normal men.


Subject(s)
Homocysteine/blood , Testosterone/pharmacology , Adult , Aromatase Inhibitors , Cross-Over Studies , Estradiol/blood , Humans , Male , Testolactone/pharmacology , Testosterone/administration & dosage , Testosterone/analogs & derivatives , Testosterone/blood
16.
Metabolism ; 46(2): 217-23, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9030832

ABSTRACT

This study examined the effect of exercise training without weight loss on high-density lipoprotein (HDL) metabolism in overweight men. We evaluated HDL metabolism using 125I-radiolabeled autologous HDL in 17 overweight men aged 40 +/- 7 years (mean +/- SD) before and after 1 year of exercise training. Subjects consumed defined diets in a metabolic kitchen during the metabolic studies. They performed endurance exercise under supervision for 1 hour four times weekly and maintained their pretraining body weight. Maximal oxygen uptake (VO2max) increased 27% (P < .001) with exercise training. HDL-cholesterol (HDL-C) and apolipoprotein (apo) A-I increased 10% and 9%, respectively (P < .001 for both), whereas triglycerides and apo B decreased 7% and 10%, respectively (P < .05). Postheparin lipoprotein lipase increased 11% (P = NS). Hepatic triglyceride lipase activity (HTGLA) decreased 12% (P < .05). The fractional catabolic rate (FCR) of HDL protein and of apo A-I decreased 5% and 7%, respectively (P < .05 for both). The synthetic rate of apo A-I increased 13% (P < .01). Increased HDL after exercise training is associated with both decreased HDL protein catabolism and increased HDL apo A-I synthesis. Weight loss is not required to increase HDL-C with exercise training in overweight men, but without weight loss, even prolonged exercise training produces only modest changes in HDL-C concentrations.


Subject(s)
Body Weight/physiology , Exercise/physiology , Lipoproteins, HDL/metabolism , Weight Loss/physiology , Adult , Apolipoproteins A/metabolism , Humans , Kinetics , Lipase/metabolism , Lipids/blood , Male
17.
Atherosclerosis ; 125(1): 91-101, 1996 Aug 23.
Article in English | MEDLINE | ID: mdl-8831931

ABSTRACT

Maintenance dialysis patients experience an exceedingly high incidence of arteriosclerotic cardiovascular disease (CVD) events that are poorly predicted by traditional CVD risk factor indices. We evaluated the prevalence of three non-traditional CVD risk factors, i.e. hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) Lp(a)) excess, and combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, in maintenance dialysis patients. Fasting total plasma homocysteine (Hcy), fibrinogen, Lp(a), glucose, and total and HDL cholesterol levels, and traditional CVD risk factor (i.e. glucose tolerance, smoking, hypertension, dyslipidemia) prevalences were assessed in 71 dialysis patients and 71 age, sex, and race matched Framingham Study controls free of clinical renal disease, with normal serum creatinine (< or = 1.5 mg/dl). Mean plasma Hcy 23.7 vs. 9.9 microM, P = 0.0001), fibrinogen (457 vs. 309 mg/dl, P = 0.0001), and Lp(a) (30 vs. 17 mg/dl, P = 0.0070) levels were substantially increased in the dialysis patients. Matched odds ratios (with 95% confidence intervals), dialysis patients/controls, for hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, alone or combined, were markedly greater in the dialysis patients, with no evidence of confounding by the traditional CVD risk factors: hyperhomocysteinemia, 105.0 (29.9-368.9); hyperfibrinogenemia, 16.6 (6.6-42.0); Lp(a) excess, 3.5 (1.5-8.4); all three combined 35.0 (5.7-199.8). Given in vitro evidence that Hcy, Lp(a), and fibrinogen interact to promote atherothrombosis, combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess may contribute to the high incidence of vascular disease sequelae experienced by dialysis patients, which is inadequately explained by traditional CVD risk factors. Controlled, prospective studies of well-characterized maintenance dialysis cohorts are urgently required to substantiate this hypothesis.


Subject(s)
Fibrinogen/metabolism , Homocysteine/blood , Kidney Failure, Chronic/blood , Lipoprotein(a)/blood , Renal Dialysis , Adult , Age Factors , Aged , Amino Acid Metabolism, Inborn Errors/complications , Arteriosclerosis/etiology , Biomarkers , Blood Coagulation Disorders/complications , Case-Control Studies , Epidemiologic Factors , Female , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Risk Factors , Sex Factors
18.
Am J Cardiol ; 77(14): 1244-7, 1996 Jun 01.
Article in English | MEDLINE | ID: mdl-8651107

ABSTRACT

We administered testosterone, with or without the aromatase inhibitor testolactone, to determine the effects of testosterone and its aromatization to estradiol on Lp(a) levels in normal men. Average Lp (a) values decreased by 37% during testosterone alone and by 28% when testosterone and testolactone were combined, suggesting that testosterone reduces Lp(a) in men primarily by an androgenic effect and not by its conversion to estradiol.


Subject(s)
Lipoprotein(a)/drug effects , Testosterone/pharmacology , Adult , Cross-Over Studies , Estradiol/metabolism , Humans , Lipoprotein(a)/blood , Male , Testosterone/metabolism
19.
J Clin Epidemiol ; 48(12): 1485-93, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8543962

ABSTRACT

Previously reported associations between abdominal adiposity and coronary heart disease (CHD) may be mediated through serum lipids. In the present longitudinal study, 43 Western Samoan men who participated in a 1982 study were recontacted for a second determination of anthropometric and serum lipoprotein cholesterol levels. The men showed dramatic increases in weight (mean change +/- SD: 10.5 +/- 8.8 kg), abdominal circumference (10.0 +/- 7.6 cm), total cholesterol (49.5 +/- 26.4 mg/dl), and non-HDL cholesterol (53.1 +/- 26.6 mg/dl). A new indicator was used to estimate changes in abdominal adiposity: the residual from the regression of change in the abdominal circumference on change in body weight (the AR). The AR was significantly correlated with changes in total (r = 0.38) and non-HDL cholesterol (r = 0.39). Changes in HDL cholesterol were correlated with changes in weight only (r = -0.37). These bivariate relations remained significant in multiple linear regression analyses. These longitudinal results are the first to suggest changes in abdominal adiposity are related to changes in total and non-HDL cholesterol levels.


Subject(s)
Adipose Tissue/pathology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Obesity/pathology , Abdomen/pathology , Adult , Anthropometry , Body Constitution , Cholesterol/blood , Coronary Disease/epidemiology , Follow-Up Studies , Humans , Independent State of Samoa/epidemiology , Longitudinal Studies , Male , Obesity/blood , Obesity/epidemiology , Risk Factors , Weight Gain
20.
Int J Obes Relat Metab Disord ; 19(10): 731-8, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8589767

ABSTRACT

OBJECTIVE: To examine relations between obesity and serum concentrations of lipoprotein cholesterol, apolipoproteins, triglycerides and insulin in American and Western Samoans. Associations are also described between these CHD risk factors and abdominal adiposity, and the potential mediating role of insulin in these relationships is examined. DESIGN: Cross-sectional, using a sub-sample from an observational epidemiological study of cardiovascular disease risk factors among Samoans. MEASUREMENT: Obesity is estimated by the body mass index (BMI), and fat distribution by the abdomen-hip circumference ratio (AHR). All biochemical parameters were measured in the fasted stated. SUBJECTS: The sub-sample is 178 men and 147 women who were free from hypertension, diabetes and heart disease. RESULTS: In multivariate linear regression analyses in men the BMI was positively associated with levels of total cholesterol, the total-HDL cholesterol ratio, apolipoprotein B, and the log of triglyceride and insulin concentrations, and negatively associated with HDL and HDL2 cholesterol. The quadratic term for BMI was also found to be significantly predictive of all metabolic parameters in men, except for the log of serum insulin concentrations. Among the women, in contrast, BMI levels were significantly associated only with concentrations of HDL2 cholesterol, triglyceride and insulin. In men, the associations between the AHR and the metabolic parameters were similar to those described for the BMI, but showed no indication of non-linearity. Addition of the log of insulin to these models had little effect on the relations between the AHR and the lipid parameters, with the exceptions of total cholesterol and triglycerides. As with BMI, the AHR was much les predictive of metabolic parameters in women than in men, with a significant relation existing only with the log of insulin concentrations. CONCLUSIONS: These cross sectional data indicate that overall and abdominal adiposity are important correlates of serum lipid parameters among Samoan men, though the associations with BMI are attenuated at higher levels. Neither anthropometric indicator has much relation with these CHD risk factors among the women, perhaps due to extremely high levels of obesity in this group.


Subject(s)
Apolipoproteins/blood , Body Composition/physiology , Insulin/blood , Lipids/blood , Adult , American Samoa/epidemiology , Apolipoproteins B/blood , Body Constitution , Body Mass Index , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Cholesterol, HDL/blood , Cross-Sectional Studies , Female , Humans , Independent State of Samoa/epidemiology , Linear Models , Male , Middle Aged , Obesity/blood , Obesity/epidemiology , Risk Factors , Triglycerides/blood
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