Positive correlation between tumor necrosis factor (TNF)-α and cardiorespiratory fitness after six-months of regular aerobic exercise in Peruvian Amerindian women / Asociación entre factor de necrosis tumoral α sérico y capacidad aeróbica en mujeres amerindias peruanas, después de seis meses de entrenamiento

Background: Adipose tissue is a source of inflammatory cytokines which may influence insulin action. Aim: To evaluate exercise effects on plasma (p)-levels of tumor necrosis factor (TNF)-α , and interleukin (IL)-6 in Peruvian Amerindian women. Material and Methods: After five years of observation during which p-glucose deteriorated and weight increased, 44 Peruvian Amerindian women aged 20-59 years took part in a 6-month exercise program. Plasma TNF-α and IL-6 had been measured 5 years earlier, and were reassessed before and after exercise, using ELISA kits. Cardiorespiratory fitness was derived from the results of the twelve minutes’ walk and expressed as maximum oxygen uptake (VO2max). Results: After the training program, estimated VO2max increased from 18.55 ± 3.79 to 20.91 ± 4.61 mL kg-1 min-1 (p < 0.01) and p-TNF-α increased from 3.2 ± 3.4 to 4.3 ± 6.6 pg/mL (p = 0.03). There were reductions in p-glucose from 5.19 ± 1.59 to 4.32 ± 1.62 mmol/L (p < 0.01) and in waist circumference (p=0.01). Weight, p-insulin, and IL-6 did not change. Levels of p-glucose and p-TNF-α observed after the training period were identical to values 5 years earlier. P-TNF-α was positively associated with estimated VO2max, prior to (r = .414, p < 0.01) as well as after (r = .362, p < 0.05) exercise, independently of adiposity. P-IL-α was associated with waist circumference but not with estimated VO2max. Conclusions: P-TNF-a correlated with estimated VO2max independently of adiposity. Beneficial effects of exercise on p-glucose were observed in spite of an increase in p-TNF-α.

Antecedentes: El tejido adiposo es una fuente de citoquinas inflamatorias, que pueden influenciar la acción de insulina. Objetivo: Evaluar el efecto del ejercicio sobre los niveles de factor de necrosis tumoral α (TNFα) e interleukina α (IL-α) en mujeres amerindias. Material y Métodos: Después de cinco años de observación, en los cuales la glicemia y el peso aumentaron, 44 mujeres amerindias de 20 a 59 años participaron en un programa de ejercicio que duró seis meses. TNFα e IL-α se habían medido cinco años antes y se re evaluaron antes y después del ejercicio, usando kits de ELISA. La capacidad cardiorespiratoria se estimó a partir de la prueba de marcha de 12 minutos y se expresó como capacidad aeróbica máxima (VO2max). Resultados: Después del programa de ejercicio, la VO2max estimada aumentó de 18,55 ± 3,79 a 20,91 ± 4,61 mL kg-1 min-1 (p < 0,01) y el TNFα aumentó de 3,2 ± 3,4 a 4,3 ± 6,6 pg/mL (p = 0,03). Se observó una reducción de la glicemia de 5,19 ± 1,59 a 4,32 ± 1,62 mmol/L (p < 0,01) y de la circunferencia de cintura (p = 0,01). El peso, insulinemia e IL-α no cambiaron. Los niveles de glicemia y TNFα observados después del período de entrenamiento, eran iguales a los determinados cinco años antes. Los niveles de TNFα se correlacionaron con el VO2max estimado antes y después del período de entrenamiento, y no dependieron de la adiposidad. Los niveles de IL-α se correlacionaron con la circunferencia de cintura pero no con el VO2max estimado. Conclusiones: Los niveles de TNFα se correlacionaron con el VO2max estimado independientemente del nivel de adiposidad. Los efectos beneficiosos del ejercicio sobre la glicemia se observaron a pesar de un aumento de los niveles de TNFα.

Positive correlation between tumor necrosis factor (TNF)-α and cardiorespiratory fitness after six-months of regular aerobic exercise in Peruvian Amerindian women.

BACKGROUND: Adipose tissue is a source of inflammatory cytokines which may influence insulin action. AIM: To evaluate exercise effects on plasma (p)-levels of tumor necrosis factor (TNF)-α , and interleukin (IL)-6 in Peruvian Amerindian women. MATERIAL AND METHODS: After five years of observation during which p-glucose deteriorated and weight increased, 44 Peruvian Amerindian women aged 20-59 years took part in a 6-month exercise program. Plasma TNF-α and IL-6 had been measured 5 years earlier, and were reassessed before and after exercise, using ELISA kits. Cardiorespiratory fitness was derived from the results of the twelve minutes' walk and expressed as maximum oxygen uptake (VO(2max)). RESULTS: After the training program, estimated VO(2max) increased from 18.55 ± 3.79 to 20.91 ± 4.61 mL kg(-1) min(-1) (p < 0.01) and p-TNF-α increased from 3.2 ± 3.4 to 4.3 ± 6.6 pg/mL (p = 0.03). There were reductions in p-glucose from 5.19 ± 1.59 to 4.32 ± 1.62 mmol/L (p < 0.01) and in waist circumference (p=0.01). Weight, p-insulin, and IL-6 did not change. Levels of p-glucose and p-TNF-α observed after the training period were identical to values 5 years earlier. P-TNF-α was positively associated with estimated VO(2max), prior to (r = .414, p < 0.01) as well as after (r = .362, p < 0.05) exercise, independently of adiposity. P-IL-α was associated with waist circumference but not with estimated VO(2max). CONCLUSIONS: P-TNF-a correlated with estimated VO(2max) independently of adiposity. Beneficial effects of exercise on p-glucose were observed in spite of an increase in p-TNF-α.

Disassociated relation between plasma tumor necrosis factor-alpha, interleukin-6 and increased body weight in Amerindian women: A long-term prospective study of natural body weight variation and impaired glucose tolerance.

BACKGROUND: Inflammatory cytokines are linked to obesity-related insulin resistance and may predict type 2 diabetes independently of obesity. We previously reported that a majority of a cohort of 73 non-diabetic women with normal plasma (p-)glucose with Amerindian heritage in Lima, Peru, during a 5-year period increased both body weight and p-glucose levels, yet p-insulin was unaltered. A high proportion of palmitoleic acid (16:1n-7) in serum (s) and systolic blood pressure (SBP) were independent predictors of high p-glucose. Whether cytokines also contributed is, however, not known. METHODS: During 5 years we prospectively investigated the relation between changed concentrations of p-tumor necrosis factor (TNF)-alpha, p-interleukin (IL)-6 and circulating insulin and glucose in relation to the natural variation of body weight. Study variables included anthropometric measurements, p-insulin, TNF-alpha, IL-6, SBP and the proportion of 16:1n-7 in s-fatty acid composition. RESULTS: Weight and waist differences correlated negatively to the difference in p-TNF-alpha but positively to differences in p-IL-6 and p-insulin, whereas the increase of p-glucose from baseline to follow-up did not correlate with changes in levels of the two cytokines. In multiple regression analysis changes of TNF-alpha and insulin contributed independently to the variance in weight. P-insulin at baseline and weight change were determinants of fasting p-insulin at follow-up. Multiple regression analysis revealed that weight change (t-value = - 2.42; P = 0.018) and waist change (t-value = 2.41; P = 0.019) together with S-16:1n-7 (p < 0.0001) and SBP (p = 0.0005) at baseline were significant predictors of p-glucose at follow-up. CONCLUSION: Our prospective study of Amerindian women revealed disassociations between changes in p-TNF-alpha and p-IL-6 in relation to variation in body weight. A high proportion of s-16:1n-7, SBP at baseline together with weight and waist changes were independent predictors of p-glucose at follow-up. The exact role of the opposite effects and clinical impact of p-TNF-alpha and p-IL-6 on loss and gain of body weight and indirectly on the development of glucose intolerance is not known.

Inflammation-sensitive plasma proteins are associated with increased incidence of heart failure: a population-based cohort study.

BACKGROUND: Although inflammation has been associated with different cardiovascular diseases, the relationships with future heart failure (HF) are unclear. This population-based study explored whether elevated plasma levels of inflammatory proteins are associated with incidence of HF. METHODS: Five inflammation-sensitive plasma proteins (ISPs, fibrinogen, ceruloplasmin, haptoglobin, orosomucoid, and alpha1-antitrypsin) was measured in 6071 men (mean age 46 years) without history of myocardial infarction (MI) or stroke. Incidence of hospitalizations due to HF (primary diagnosis) was monitored over 22 years of follow-up, in relation to the number of elevated ISPs (i.e., in the 4th quartile). Subjects with myocardial infarction during follow-up were censored. RESULTS: During the follow-up, 159 men were hospitalized due to HF. Baseline levels of all ISPs, except for haptoglobin, were significantly higher in men who developed HF. After adjustments for confounding factors, the hazard ratios (HR) of HF were 1.00 (reference), 1.7 (95% CI: 1.1-2.7), 2.0 (CI: 1.2-3.3) and 2.6 (CI: 1.6-4.1), respectively, in men with none, one, two and three or more ISPs in the 4th quartile (trend: p<0.001). Of the individual ISPs, fibrinogen, ceruloplasmin and alpha1-antitrypsin showed significant relationships with incidence of HF after adjustment for risk factors. CONCLUSION: Plasma levels of inflammatory markers are associated with long-term incidence of hospitalizations due to HF in middle-aged men.

Complement C3 and C4 in plasma and incidence of myocardial infarction and stroke: a population-based cohort study.

BACKGROUND: Complement factor C3 and C4 have been associated with atherosclerosis and cardiovascular risk factors. This study explored whether plasma levels of C3 and C4 are risk factors for the incidence of cardiovascular disease (CVD). DESIGN: A population-based prospective study of 5850 initially healthy men, 28-61 years old at baseline. METHODS: Plasma levels of C3 and C4 were analysed at the baseline examination. The incidence of coronary events (i.e. fatal or non-fatal myocardial infarction), ischaemic stroke and cardiovascular events (i.e. myocardial infarction, ischaemic stroke or cardiovascular death) was studied over 18 years of follow-up. RESULTS: Adjusted for age, C3 in the fourth quartile (versus the first quartile) was associated with an increased incidence of coronary events [relative risk (RR) 1.54, 95% confidence interval (CI) 1.2-1.9], cardiovascular events (RR 1.56, 95% CI 1.3-1.9), and non-significantly with the incidence of ischaemic stroke (RR 1.31, 95% CI 0.89-1.8). However, after adjustments for smoking, body mass index (BMI), cholesterol, diabetes and systolic blood pressure, these relationships were completely attenuated and non-significant. The relationships were similar for C4 concentrations within the normal range. However, for men with C4 in the top 10% of the distribution (>0.34 g/l), a significantly increased incidence of coronary events was found, which persisted after adjustments for risk factors. CONCLUSION: C3 and C4 show substantial correlations with cardiovascular risk factors, including blood pressure, BMI, and lipids. This relationship accounts for the increased incidence of CVD in men with high C3 levels. However, very high C4 levels may be associated with the incidence of CVD, independently of traditional cardiovascular risk factors.

Long-term change in cholesterol in relation to inflammation-sensitive plasma proteins: a longitudinal study.

PURPOSE: The nature of the relationship between inflammation and elevated serum lipid levels is incompletely understood. This longitudinal study explores whether elevated levels of inflammation-sensitive plasma proteins (ISPs) are a risk factor for developing increased cholesterol and triglyceride levels. METHODS: Five ISPs (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin) were measured in a population-based cohort of nondiabetic healthy men aged 38 to 50 years at baseline. Subjects were reexamined after a mean of 6.2 years. The development of hypercholesterolemia (cholesterol>or=6.5 mmol/L [>or=251 mg/dL]) and hypertriglyceridemia (triglycerides>or=2.3 mmol/L [>or=204 mg/dL]) during follow-up was studied in relation to the number of elevated levels of ISPs (i.e., in the top quartile). RESULTS: Of men with initially normal cholesterol levels (<6.5 mmol/L; n=2224), proportions of men with no, one, two, and three or more elevated ISP levels at baseline who developed hypercholesterolemia were 12%, 13%, 16%, and 20%, respectively (p for trend=0.0002). This relationship remained significant after adjustments for cholesterol level at baseline and other confounding factors. The relationship between ISP levels and future hypertriglyceridemia was attenuated and nonsignificant after adjustments for confounding factors. CONCLUSION: In apparently healthy men with initially normal cholesterol levels, elevated ISP levels are a risk factor for development of hypercholesterolemia.

Serum cholesteryl fatty acid composition and plasma glucose concentrations in Amerindian women.

BACKGROUND: Diabetes mellitus has reached epidemic proportions in women of Amerindian origin. The risk of developing diabetes has been found to be related to the serum fatty acid composition in whites. OBJECTIVE: We prospectively investigated the relation between the serum cholesteryl fatty acid composition and changes in fasting plasma glucose concentrations in Peruvian Indian women who are characterized by hyperinsulinemia in comparison to white women. DESIGN: A 5-y follow-up study of 73 women with normal fasting plasma glucose values was undertaken by performing a survey in 1999 and a follow-up survey in 2004. The studied variables included anthropometric measurements, plasma insulin and leptin, dietary food consumption from 24-h recall, blood pressure, and serum fatty acid composition. RESULTS: The participants developed significantly higher fasting plasma glucose concentrations in 2004 compared with 1999 (P < 0.0001) with unaltered plasma insulin values. Palmitoleic acid (16:1n-7) in 1999 was the only fatty acid that was significantly correlated to glucose concentration at follow-up. In a multiple regression analysis that included waist circumference, percentage of body fat, systolic blood pressure, and circulating triacylglycerol, insulin, leptin, and 16:1n-7 as independent determinants, 16:1n-7 and systolic blood pressure were the only significant determinants of plasma glucose concentration 5 y later. CONCLUSIONS: A high proportion of 16:1n-7 in serum is an independent predictor of high plasma glucose concentrations in Amerindian women. The reason for this association remains to be elucidated.

Occupation, marital status, and low-grade inflammation: mutual confounding or independent cardiovascular risk factors?

OBJECTIVE: We explored the relationships between inflammatory proteins, occupation, and marital status, and their independent associations with incidence of cardiovascular disease (CVD). METHODS AND RESULTS: Five inflammation-sensitive proteins (ISPs) (fibrinogen, ceruloplasmin, haptoglobin, alpha1-antitrypsin, orosomucoid) were measured in 6075 apparently healthy men. Incidence of coronary events and stroke was followed over 18 years in relation to occupation and marital status. All ISPs showed higher concentrations in divorced men and in manual workers. Except for fibrinogen, this remained significant after adjustments for confounding factors. Adjusted for traditional cardiovascular risk factors, incidence of coronary events was significantly increased in unskilled manual workers and in divorced men. The relative risks were slightly reduced after further adjustments for ISPs (from 1.79 to 1.70 in unskilled manual workers; from 1.58 to 1.51 in divorced men). All ISPs were significantly associated with incidence of coronary events, after adjustments for traditional risk factors. This relationship was essentially unchanged after further adjustments for occupation and marital status. CONCLUSIONS: Inflammation could contribute to, but not fully explain, the increased cardiovascular risk in manual workers and divorced men. Although the ISPs vary greatly by occupational and marital status, this does not confound the relationship between ISPs and incidence of CVD.

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.

Complement C3 is a risk factor for the development of diabetes: a population-based cohort study.

Cross-sectional studies have reported strong correlations between plasma levels of complement C3, insulin, and glucose. This prospective study explored whether elevated levels of C3, C4, and other inflammation-sensitive plasma proteins (ISPs; fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with the development of diabetes. Plasma proteins were measured in 2,815 nondiabetic healthy men, age 38-50 years, who were reexamined after a mean follow-up of 6.1 years. Diabetes development (n = 123) was studied in relation to baseline levels of plasma proteins. After adjusting for age, screening year, and glucose at baseline, the odds ratio (95% CI) for developing diabetes was 1.00, 2.4 (1.1-5.3), 2.9 (1.4-6.0), and 5.6 (2.8-10.9), respectively, for men with C3 in the 1st, 2nd, 3rd, and 4th quartiles (trend: P < 0.00001). Fibrinogen, haptoglobin, C4, and the number of elevated ISPs were also related to future diabetes in this model. Only C3 was significantly associated with diabetes development after further adjustments for potential confounders, including BMI, insulin, and other inflammatory markers. We concluded that the risk of developing diabetes is related to levels of complement C3.

Risk of treatment of peripheral arterial disease is related to inflammation-sensitive plasma proteins: a prospective cohort study.

BACKGROUND: Studies in patients with peripheral arterial disease (PAD) have reported an association between inflammatory markers and severity of disease or worsening of symptoms. However, few have studied the prognostic significance of inflammatory markers in asymptomatic subjects, measured many years before the onset of symptomatic PAD requiring treatment (trPAD). MATERIAL AND METHODS: Five inflammation-sensitive plasma proteins (ISPs), including fibrinogen, alpha 1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid, were determined in 5619 healthy men (mean age, 46.8 +/- 3.7 years) without walking-induced calf pain. Data for men who subsequently underwent a revascularization procedure because of trPAD (intermittent claudication or critical ischemia) were retrieved from hospital-based registers. Future trPAD was studied in relation to the number of ISPs in the top quartile at the baseline examination. RESULTS: Seventy men (1.2%) underwent revascularization because of trPAD at a mean of 16.5 years after the baseline examination. The proportion with future trPAD was 0.4%, 1.0%, 1.5%, and 3.2%, respectively, for men with 0, 1, 2, and 3 or more ISPs in the top quartile (trend, P < .0001). After adjustment for age, screening year, systolic blood pressure, blood pressure medication, cholesterol concentration, diabetes, smoking, and tobacco consumption the corresponding odds ratios (95% confidence interval [CI]) were 1.00 (reference), 1.5 (CI, 0.7-3.6), 1.9 (CI, 0.8-4.6), and 2.9 (CI, 1.3-6.4), respectively, in these groups (trend, P = .003). CONCLUSION: Elevated ISPs, measured 16 years earlier in apparently healthy men without walking-induced calf pain, were associated with increased risk for development of PAD requiring revascularization.

Traditional versus agricultural lifestyle among Shuar women of the Ecuadorian Amazon: effects on leptin levels.

Leptin is a key biological marker related to energy balance and development of diabetes and cardiovascular diseases. Its levels are increased in populations with a high degree of the metabolic syndrome. Life history of evolution has, however, largely taken place under the ecological context of hunting and gathering. In this study, we explored whether the first steps of transition to sedentary agriculture involve a change of body composition, plasma leptin concentration, and markers of the metabolic syndrome. A total of 59 healthy Shuar Amerindian women living in 5 isolated communities in the Ecuadorian Amazonian rain forest were examined. Women (n = 33) from the largest and oldest community, Yuwientsa, who are more dependent on agriculture had higher fat mass (11.7 +/- 3.3 v 14.5 +/- 4.0 kg; P = .023) but the same body mass index (24.1 +/- 2.7 v 23.1 +/- 2.8 kg/m2; not significant [NS]) and lean body mass (41.0 +/- 5.0 v 40.2 +/- 6.2 kg; NS) than women (n = 26) from the 4 traditional hunter/gather settlements. Furthermore, women from Yuwientsia had higher leptin (5.5 +/- 3.1 v 4.1 +/- 2.7 ng/mL; P = .021) and plasma insulin levels (49.8 +/- 37.4 v 35.5 +/- 12.7 pmol/L; P = .013). Homeostasis model assessment (HOMA) values (8.8 +/- 4.8 v 6.1 +/- 2.2; P = .004) and plasma triglyceride levels (2.3 +/- 1.0 v 1.7 +/- 0.6 mmol/L; P = .025) as markers of the metabolic syndrome were also increased in the Yuwientsa population. Mean plasma glucagon concentrations were not different between the groups. We conclude that body fat and levels of insulin and leptin are higher in the population more dependent on agriculture for living. In fact, the leptin concentrations from the 4 hunter/gather communities are the lowest mean value ever reported from a population of healthy females. As there are no genetic or biologic differences between the Shuar Indians from the 5 communities, we hypothesize that behavioral responses to a changing environment may be the key to the development of the metabolic syndrome and elevated plasma leptin concentrations.

Fatality of future coronary events is related to inflammation-sensitive plasma proteins: a population-based prospective cohort study.

BACKGROUND: Approximately 40% of men suffering a first acute coronary event die the first day; most of them never reach hospital. It is largely unknown whether a low-grade inflammation in healthy men predicts the fatality of future coronary events. METHODS AND RESULTS: Five inflammation-sensitive plasma proteins (ISPs; fibrinogen, orosomucoid, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin) were measured in 6075 apparently healthy men, 680 of whom had a first coronary event [nonfatal myocardial infarction (MI) or death from coronary heart disease (CHD)] over a mean follow-up of 19 years. Of the 680 men who had a coronary event, 197 died the first day and 228 died within 28 days. Elevated ISPs were significantly associated with both nonfatal MI and CHD death, but the relative risks for CHD death were higher than for nonfatal MI. Among men who subsequently had a coronary event, the proportion of fatal events was related to the number of elevated ISPs at the baseline examination. The proportions who died the first day were 26%, 25%, 29%, and 35%, respectively, among men with 0, 1, 2, and > or =3 elevated ISPs (trend: P=0.01, adjusted for risk factors). The corresponding proportions who died within 28 days were 30%, 31%, 34%, and 38%, respectively (trend: P=0.03). CONCLUSIONS: Men who have been exposed to a low-grade inflammation many years earlier have higher fatality in future coronary events, with a higher proportion of CHD deaths and less nonfatal MI. This relation should be regarded when inflammatory markers are considered for risk assessment in primary prevention.

Incidence of obesity-associated cardiovascular disease is related to inflammation-sensitive plasma proteins: a population-based cohort study.

BACKGROUND: Although obesity is associated with increased inflammation, it is unclear whether this accounts for the increased cardiovascular risk in obesity. This population-based study explored whether inflammation-sensitive plasma proteins (ISPs) modify the cardiovascular risk in overweight or obese men. METHODS AND RESULTS: The ISPs (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, ceruloplasmin) were measured in 6075 healthy men, aged 28 to 61 years. The incidences of cardiovascular events (myocardial infarction, stroke, cardiovascular deaths), cardiac events (fatal or nonfatal myocardial infarction), and stroke were followed-up over 18+/-4 years. High ISPs were associated with an increased cardiovascular risk in all categories of body mass index (BMI). The age-adjusted relative risks for cardiovascular events in obese men (BMI >30) were 2.1 (95% CI, 1.4 to 3.4), 2.4 (CI, 1.5 to 3.7), 3.7 (CI, 2.3 to 6.0), and 4.5 (CI, 3.0 to 6.6), respectively, for those with 0, 1, 2, and > or =3 ISPs in the top quartile (trend P=0.002) (reference: BMI <25 and no elevated ISP). This trend persisted after adjustments for several potential confounders (P=0.02). Incidence of cardiac events showed similar relations with the number of elevated ISPs in obese men. CONCLUSIONS: The cardiovascular risk varies widely between obese or overweight men with high and low ISPs. Relationships with ISPs contribute to, but cannot fully explain, the increased cardiovascular risk in obese men.

Body adiposity, insulin, and leptin in subgroups of Peruvian Amerindians.

Migration of aboriginal populations is thought to increase the risk of obesity and associated disorders. In this study, we examined body adiposity, glucose, insulin, leptin, and blood pressure in adult Quechua females living in rural villages in the Cuzco region [n = 105, age 35 +/- 10 yr (SD) years] and after migration to Lima from Peruvian Central Andes (n = 105, age 37 +/- 10 yr). The two populations are of the same origin and have similar fat composition in their diet, but they differ in degree of physical activity (high in Cuzco, low in Lima) and altitude of living (highland in Cuzco, lowland in Lima). The two groups had similar BMI (24.6 +/- 3.9 kg/m(2) in Cuzco vs. 25.1 +/- 4.7 kg/m(2) in Lima) and waist circumference (83.1 +/- 9.8 cm in Cuzco vs. 83.7 +/- 10.6 cm in Lima). Yet women in Lima had increased body fat mass (17.7 +/- 5.3 kg in Cuzco vs. 21.5 +/- 5.8 kg in Lima, p < 0.001) and higher diastolic blood pressure, glucose, insulin, and leptin (all p < 0.001). Also the HOMA assessment of insulin resistance was higher in Lima (p < 0.001). We conclude that migration of Peruvian Amerindian women from the Cuzco region to Lima is associated with increased risk for obesity and cardiovascular diseases without being associated with higher BMI and waist circumference.

Incidence of fatal or repaired abdominal aortic aneurysm in relation to inflammation-sensitive plasma proteins.

UNLABELLED: Background- Inflammation is an important pathophysiological feature of abdominal aortic aneurysms (AAA). Whether elevated levels of inflammation-sensitive plasma proteins (ISPs) predict the long-term risk of fatal or repaired AAA is largely unknown. METHODS AND RESULTS: Five ISPs (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin) were measured in 6075 healthy men, mean age 46.8+/-3.7 years. After a mean time of 19 years, 63 men had a fatal or surgically/endovascularly repaired AAA. Risk of treatment or death from future AAA was studied in relation to the ISPs. The risk of future AAA increased significantly with the number of elevated ISPs (ie, in the top quartile). The proportions with future AAA were 0.4%, 1.0%, 1.3%, and 2.3% for men with none, one, two, and > or =3 ISPs, respectively, in the top quartile (trend: P<0.0001). The corresponding odds ratios were 1.00 (reference), 1.9 (95% CI: 0.8 to 4.5), 2.2 (0.9 to 5.5), and 3.2 (1.4 to 7.2), respectively, adjusted for age, screening year, smoking, cholesterol, triglycerides, systolic blood pressure and physical inactivity (trend: P=0.004). CONCLUSIONS: The incidence of fatal or repaired AAA is associated with the ISP levels. In this population-based study, elevated ISPs could be observed many years before the clinical manifestation of disease.

Inflammation-sensitive plasma proteins and incidence of myocardial infarction in men with low cardiovascular risk.

OBJECTIVE: Myocardial infarction (MI) is sometimes experienced by individuals without any traditional risk factor. This prospective study explored whether incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and serum lipids is related to inflammation-sensitive plasma proteins (ISPs). METHODS AND RESULTS: Five ISPs (alpha1-antitrypsin, haptoglobin, ceruloplasmin, fibrinogen, orosomucoid) were analyzed in 6075 men, 47+/-3.6 years old. A low-risk group (no traditional risk factor, n=1108) and a high-risk group (> or =2 major risk factors, n=1011) were defined. Incidence of MI (n=227) was monitored over 18.1+/-4.3 years of follow-up. In the low-risk group, the age-adjusted relative risks (RRs) were 1.00 (reference), 1.9 (95% CI, 0.8 to 4.2), 1.8 (95% CI, 0.6 to 5.4), and 2.9 (95% CI, 1.05 to 8.1), respectively, for men with 0, 1, 2 and > or =3 ISPs in the top quartile (trend: P=0.03). In this group, the increased risk was observed only after > or =10 years of follow-up. In the high-risk group, the age-adjusted RRs were 1.00, 1.4 (95% CI, 0.9 to 2.2), 1.9 (95% CI, 1.2 to 3.1), and 2.0 (95% CI, 1.3 to 3.1), respectively, for men with 0, 1, 2, and > or =3 ISPs in the top quartile (trend: P=0.0004). CONCLUSIONS: Incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and lipids was related to ISPs. The causes for this relationship remain to be explored.

Risk of myocardial infarction in relation to plasma levels of homocysteine and inflammation-sensitive proteins: a long-term nested case-control study.

Several studies have found that the homocysteine plasma level is associated with cardiovascular disease. The authors previously described a relationship between concentrations of fibrinogen and other inflammation-sensitive plasma proteins, namely, alpha1-antitrypsin, ceruloplasmin, haptoglobin, and orosomucoid (alpha1-acid glucoprotein) and the incidence of myocardial infarction (MI). Whether levels of these proteins are related to homocysteine has not been clarified. The aim of this study was to investigate whether a supposed relationship between homocysteine in plasma and the occurrence of MI is modified by these inflammation-sensitive proteins. A nested case-control study was designed, comprising 241 cases of MI, with a mean age of 48 years at baseline, and 241 controls matched for age, month of examination, and duration of follow-up. The mean homocysteine concentration did not differ between cases and controls and there was no association between the baseline homocysteine level and the time lapse before the occurrence of the MI. For the cases, there was no correlation between homocysteine and any of the measured proteins, but for the controls, homocysteine was weakly but significantly negatively correlated to haptoglobin and ceruloplasmin and slightly positively correlated to albumin. For the separated groups of cases and controls there was no association between the number of inflammation-sensitive proteins in the top quartiles and homocysteine concentration. In this population-based, prospective cohort study the occurrence of MI had no relationship to homocysteine baseline plasma level. Furthermore, there was no strong association between homocysteine and the concentrations of any of these inflammation-sensitive proteins.