Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women.

BACKGROUND AND AIMS: Two Amerindian populations--Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women. METHODS AND RESULTS: Fasting plasma was used for analyses of glucose, insulin, leptin and fatty acid composition. Women in Lima had more body fat, higher fasting insulin and leptin and lower insulin sensitivity than the Shuar women, who had insulin sensitivity similar to Swedish women. Shuar women had very high proportions (mean; SD) of palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase was about twice as high in the Shuar compared with Lima women, suggesting neo lipogenesis, while the delta 5 desaturase activity did not differ. The Lima women, as well as the Swedish, showed strong positive correlations between SCD-1 activity on the one hand and fasting insulin and HOMA index on the other. These associations were absent in the Shuar women. CONCLUSIONS: The high SCD-1 activity in the Shuar women may reflect increased lipogenesis in adipose tissue. It also illustrates how a low fat diet rich in non-refined carbohydrates can be linked to a good metabolic situation.

Plasma markers of inflammation and incidence of hospitalisations for COPD: results from a population-based cohort study.

BACKGROUND: The relationship between plasma markers of inflammation and the incidence of chronic obstructive pulmonary disease (COPD) is still unclear. This population-based study explored whether raised levels of five inflammation-sensitive plasma proteins (ISPs) predicted hospital admissions for COPD during 25 years of follow-up. METHODS: Spirometric tests and measurements of five ISPs (fibrinogen, ceruloplasmin, alpha(1)-antitrypsin, haptoglobin, orosomucoid) were performed in 5247 apparently healthy men from the city of Malmö (mean age 46 years). The incidence of hospitalisations for COPD was studied in relation to the number of ISPs in the fourth quartile. RESULTS: During the follow-up period, 258 men were admitted to hospital with COPD, 211 of whom were smokers at baseline. The incidence of hospital admissions for COPD was significantly associated with the number of raised ISPs. Adjusted for risk factors, the hazards ratio (95% CI) was 1.00 (reference), 1.28 (0.9 to 1.9), 1.29 (0.8 to 2.0) and 2.30 (1.6 to 3.2), respectively, for men with 0, 1, 2 and >or=3 ISPs in the top quartile (p for trend <0.001). This relationship was consistent in men with high and low lung function at baseline. The relationship with the incidence of hospital admissions for COPD was largely the same for all individual ISPs. CONCLUSION: Raised plasma ISP levels are associated with an increased incidence of COPD requiring hospitalisation.

Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study.

Hypertension has been associated with raised plasma levels of complement factor 3 and 4 (C3 and C4). The nature of this association is unclear. This population-based longitudinal study explored whether C3 or C4 is associated with development of hypertension. Blood pressure and plasma levels of C3 and C4 were determined in 2178 healthy men, aged 35-50 years, initially without treatment for hypertension. Incidence of hypertension and blood pressure increase over 15.7 (+/-2.2) years follow-up was studied in relation to C3 and C4 at baseline. Among men with initially normal blood pressure (<160/95 mm Hg), incidence of hypertension (>or=160/95 mm Hg or treatment) was 32, 42, 37 and 47%, respectively, for men with C3 in the first, second, third and fourth quartile (trend: P=0.001). This relationship remained significant after adjustment for confounding factors. Among men without blood pressure treatment, systolic BP increase (mean+standard error, adjusted for age, initial blood pressure and follow-up time) was 17.5+0.8, 19.6+0.9, 19.8+0.8 and 20.8+0.8 mm Hg, respectively, in the C3 quartiles (trend: P=0.004). C3 was not associated diastolic blood pressure at follow-up. Although C4 was associated with blood pressure at the baseline examination, there was no relationship between C4 and development of hypertension or future blood pressure increase. It is concluded that C3 in plasma is associated with future blood pressure increase and development of hypertension.

Fatality of acute coronary events in relation to hypertension and low-grade inflammation: a population-based cohort study.

Hypertension has been associated with increased case-fatality rates among individuals who subsequently suffer from acute coronary events. It is unknown whether inflammation modifies this relationship. This population-based study explored the effects of inflammation and hypertension on incidence of coronary event, and on the fatality of the future events. Blood pressure (BP) and five inflammation-sensitive plasma proteins (ISPs, fibrinogen, orosomucoid, alpha 1-antitrypsin, haptoglobin and ceruloplasmin) were determined in 6071 healthy men. During the mean follow-up of 19 years, 679 men had a first coronary event (non-fatal myocardial infarction or death from coronary heart disease). Of them, 197 (29%) were fatal cases (death during the first day). As expected, hypertension was associated with increased incidence of coronary events and increased proportion of fatal cases. At all levels of BP, high ISPs (> or =2 ISPs in top quartile) significantly added to the incidence of events. Men with high ISPs had the highest case-fatality rates. The difference in case-fatality rate between men with and without high ISPs was, however, significant only in men with normal BP (<130/85 mm Hg) (33 vs 19%, P < 0.05), and not in men with moderate or severe hypertension (> or =160/100 mm Hg) (40 vs 35%, P = 0.32). High ISPs add to the incidence of coronary events at all levels of BP. Hypertension and inflammation are both independently associated with increased case-fatality in subjects who later have an acute coronary event. The influence of ISPs on the case-fatality rate seems to be most important in men with normal BP.

Weight gain in relation to plasma levels of complement factor 3: results from a population-based cohort study.

AIMS/HYPOTHESIS: Mice that are deficient for complement factor 3 (C3) have shown resistance to weight gain, despite increased food intake. Cross-sectional studies of humans have reported correlations between C3 and obesity. This longitudinal study explored whether C3 predicts a large weight gain in middle-aged men. METHODS: Plasma concentrations of C3 and complement factor 4 (C4) were measured in 2,706 non-diabetic healthy men aged between 38 and 50 years, who were re-examined after a mean period of 6.1 years. RESULTS: After adjustments for initial weight, age, height and follow-up time, the odds of incurring large weight gain (75th percentile, > or =3.8 kg) were 1.00 (reference), 0.96 (95% CI:0.7-1.2), 1.1 (CI:0.9-1.5) and 1.4 (CI:1.1-1.8), respectively, among men with C3 levels in the first, second, third and fourth quartiles (p for trend=0.01) respectively. This relationship remained significant after further adjustments for lifestyle factors (physical inactivity, alcohol, smoking), metabolic factors (glucose or homeostasis model assessment values, cholesterol, triglycerides), inflammatory markers (fibrinogen, haptoglobin, ceruloplasmin, orosomucoid, alpha1-antitrypsin) and for C4. C4 was associated with weight gain after adjustments for initial weight, height, follow-up time and lifestyle factors, but not after adjustments for C3. CONCLUSIONS/INTERPRETATION: C3 is a risk factor for incurring large weight gain in middle-aged men.

Risk of myocardial infarction and stroke in smokers is related to plasma levels of inflammation-sensitive proteins.

BACKGROUND: The extent to which differences in cardiovascular risk between smokers with similar daily tobacco consumption may be related to plasma levels of inflammation-sensitive proteins (ISP) and whether these proteins are associated with levels of carboxyhemoglobin (COHb%) have not been clarified. METHODS AND RESULTS: In a population-based cohort of 1489 never smokers, 1685 former smokers, and 2901 current smokers, aged 28 to 61 years, plasma levels of orosomucoid (alpha(1)-acid glycoprotein), alpha(1)-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. COHb% levels were available for 2098 of them. Incidence of myocardial infarction, stroke, and death were monitored over 18.7+/-4.7 years. The proportion with high ISP levels (ie, > or =2 ISP in the top quartile) increased progressively with daily tobacco consumption (P<0.01) and COHb% (P<0.01). In all smoking categories, the incidence of stroke, cardiac events, and death was related to ISP. In heavy smokers, high ISP levels were associated with adjusted relative risks of 1.57 (1.05 to 2.35) and 1.50 (1.11 to 2.03) for cardiac events and death, respectively. Corresponding figures for moderate and light smokers were 1.59 (1.13 to 2.24) and 1.14 (0.87 to 1.49), respectively, and 1.32 (0.95 to 1.85) and 1.48 (1.10 to 1.98), respectively. CONCLUSIONS: ISP levels are related to COHb% in smokers. High levels are associated with an increased cardiovascular risk.

Decreasing levels of tumour necrosis factor alpha and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors.

AIM: Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F2alpha during BMI lowering with orlistat (Xenical(R), Roche) or placebo. METHODS: TNF-alpha, IL-6, and 8-epi PGF2alpha evaluated in 376 subjects aged 18-75 years with BMI 28-38 kg/m2 before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily. RESULTS: Weight reduction was associated with decreasing (p < 0.001) levels of TNF-alpha and IL-6 in both orlistat and placebo groups. After 12 months, TNF-alpha was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-alpha correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF2alpha correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001). CONCLUSION: Weight reduction was associated with decreasing levels of both TNF-alpha and IL-6. After 12 months of treatment, TNF-alpha levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.

Long-term effects of inflammation-sensitive plasma proteins and systolic blood pressure on incidence of stroke.

BACKGROUND AND PURPOSE: The present study investigated the relationships between inflammation-sensitive plasma proteins (ISPs) and systolic blood pressure (SBP), as well as the joint long-term effects of ISP and SBP on incidence of stroke. METHODS: BP and 5 ISPs (fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, orosomucoid) were assessed in 6071 healthy men 28 to 61 years of age. All-cause mortality and incidence of stroke were monitored over a mean follow-up of 18.7 years in men defined by SBP (<120, 120 to 139, >/=140 mm Hg) and ISP (0 to 1 or 2 to 5 ISPs in the top quartile). RESULTS: SBP and diastolic BP were significantly and positively associated with the number of ISPs in the top quartile. As expected, elevated SBP was associated with an increased incidence of stroke. Among men with SBP >/=140 mm Hg, there were, however, significant differences between those with high and low ISP levels. After risk factor adjustment, men with SBP >/=140 mm Hg and high ISP levels had a relative risk of stroke of 4.3 (95% CI, 2.3 to 7.8) compared with men with SBP <120 mm Hg and low ISP levels. In the absence of high ISP levels, the risk associated with SBP >/=140 was 2.5 (95% CI,1.4 to 4.6). Men with high ISP levels had a significantly increased risk of stroke also after exclusion of the events from the first 10 years of follow-up. CONCLUSIONS: High ISP levels are associated with elevated BP. These proteins are associated with an increased risk of stroke among men with high BP and provide information on stroke risk even after many years of follow-up.

Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma proteins.

BACKGROUND: The inverse relationship between pulmonary function and incidence of cardiovascular disease remains largely unexplained. This prospective study explored the hypothesis of a relationship with inflammation-sensitive plasma proteins. METHODS AND RESULTS: Forced vital capacity (FVC) and plasma levels of fibrinogen, alpha(1)-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 5064 healthy men aged 28 to 61 years. All-cause mortality, cardiovascular mortality, and incidence of myocardial infarction were monitored over a mean follow-up period of 18.4 years. Low FVC (fourth quartile) was associated with higher protein levels and with increased incidences of myocardial infarction and cardiovascular death. Adjustments for protein levels reduced the age-adjusted relative risks (RRs) for myocardial infarction (from 1.99, 95% CI 1.5 to 2.6, to 1.70, 95% CI 1.3 to 2.2) and cardiovascular death (from 2.71, 95% CI 1.9 to 3.9, to 2.28, 95% CI 1.6 to 3.3) among men with low FVC, corresponding to approximately 25% of the excess risk. The risk factor-adjusted RRs were reduced from 1.45 (95% CI 1.1 to 1.9) to 1.38 (95% CI 1.1 to 1.8) and from 1.96 (95% CI 1.4 to 2.8) to 1.85 (95% CI 1.3 to 2.7) for myocardial infarction and cardiovascular death, respectively, corresponding to approximately 10% to 15% of the excess risk. Among men with low FVC, the risk factor-adjusted RR for myocardial infarction was 2.5 (95% CI 1.7 to 3.6) for those with high protein levels (> or =2 proteins in top quartile) and 1.7 (95% CI 1.1 to 2.4) for those with low protein levels (< or =1 protein in top quartile; reference, top quartile of FVC and low protein levels). CONCLUSIONS: FVC is significantly and inversely associated with plasma levels of inflammation-sensitive plasma proteins. This relationship contributes to but cannot fully explain the increased cardiovascular risk among men with low FVC.

Decreasing plasma endothelin-1 and unchanged plasma neopterin during folate supplementation in hyperhomocysteinemia.

BACKGROUND: Hyperhomocysteinemia is a risk factor for atherosclerosis and venous thrombosis, probably exerting its effects through endothelial function. Homocysteine levels are lowered by folate supplementation, and such treatment improves endothelial function. However, whether folate supplementation decreases vascular risk and improves survival is unknown. The aim of this study was to evaluate endothelial function and mononuclear leukocyte inflammatory activity during homocysteine lowering in patients with hyperhomocysteinemia and vascular disease. METHODS: Endothelial function assessed as plasma (p-)endothelin(ET)-1 and intraplatelet cGMP and cAMP, and mononuclear leukocyte inflammatory activity, assessed as p-neopterin were studied during homocysteine lowering in 50 patients with hyperhomocysteinemia and vascular disease, randomized to folate supplementation or no treatment for 3 months. RESULTS: P-homocysteine decreased during the 3 months not only in patients on folate supplementation (from 27 [21-52] to 14 [8-41] micromol/l; p<0.001), but also in the untreated group (from 23 [20-35] to 19 [4-31] micromol/l; p<0.001). P-ET-1 decreased during folate supplementation (from 5.7 [2.7-11.6] to 4.1 [1.8-9.0] pg/ml; p<0.01), but was unchanged in the untreated group 4.1 [2.0-9.5] pg/ml and 4.5 [2.7-7.1] pg/ml). P-neopterin was unchanged in patients on folate supplementation (9.7 [5.1-54.4] and 7.6 [5.7-73.0] nmol/l), but increased in the untreated group (from 8.2 [4.7-19.5] to 8.6 [4.6-24.6] nmol/l; p<0.05). Intraplatelet cGMP decreased in patients on folate supplementation (from 0.86 [0.21-2.00] platelets to 0.56 [0.17-1.42] pmol/10(9) platelets; p<0.05), but was unchanged in the untreated group. No significant differences concerning intraplatelet cAMP occurred in either group. CONCLUSIONS: Folate supplementation in hyperhomocysteinemia is associated with decreasing levels of both ET-1 and intraplatelet cGMP, and the absence of an increase in the levels of the inflammatory mediator neopterin.

Clinical manifestations of atherosclerosis in an elderly population are related to plasma neopterin, NGAL and endothelin-1, but not to Chlamydia pneumoniae serology.

BACKGROUND: Inflammatory mediators secreted by leukocytes are implicated in atherogenesis. Chlamydia (C.) pneumoniae infection has been suggested as a trigger of this process. We investigated relationships between C. Pneumoniae serology, inflammatory mediators and symptomatic cardiovascular disease in old age. METHODS: In a cross-sectional study at baseline with a prospective 4 year follow-up, intraplatelet cyclic 3'-5'adenosine monophosphate (cAMP) and cyclic 3'-5'guanosine monophosphate (cGMP), plasma neutrophil gelatinase associated lipocalin (NGAL), plasma soluble tumor necrosis factor receptor-1 (TNFR-1) plasma neopterin and plasma endothelin-1 (ET-1) were analysed together with IgG and IgA antibodies for C. Pneumoniae in an elderly reference population (n=140, median age 71 years, 71 females). Twenty-one subjects had clinical manifestations of cardiovascular disease at baseline and another 21 were diagnosed with cardiovascular disease during follow-up. RESULTS: In age adjusted logistic regression, subjects with cardiovascular disease showed higher plasma levels of neopterin (p=0.02), NGAL (p=0.04), and ET-1 (p<0.01). If subjects with cardiovascular disease at baseline were excluded from the analysis, higher plasma neopterin (p=0.01) and lower serum HDL cholesterol (p=0.03) predicted cardiovascular disease during follow-up. The presence of IgG or IgA against C. pneumoniae was not associated with cardiovascular disease. Neither were there any associations between inflammatory or endothelial parameters and C. pneumoniae serology. CONCLUSIONS: The inflammatory mediators neopterin and NGAL and endothelial derived vasoconstrictive ET-1 were increased in elderly subjects with symptomatic cardiovascular disease. Increased plasma neopterin predicted cardiovascular disease during follow-up. No relationships were found between C. Pneumoniae serology and cardiovascular disease.

Effects of cholesterol and inflammation-sensitive plasma proteins on incidence of myocardial infarction and stroke in men.

BACKGROUND: Although cholesterol is a major cardiovascular risk factor, its association with stroke remains controversial. This study explored whether the cholesterol-related incidence of stroke and myocardial infarction is modified by plasma markers of inflammation in a large, population-based cohort with a long follow-up. METHODS AND RESULTS: Plasma cholesterol and 5 inflammation-sensitive plasma proteins (ISP) (fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid) were determined in 6063 healthy men, 28 to 61 years of age. The incidence of stroke, cardiac events (fatal and nonfatal), and cardiovascular deaths was compared between groups defined by levels of cholesterol and ISP. Mean follow-up was 18.7 years. High ISP level was defined as 2 to 5 ISP in the top quartile. High cholesterol was associated with higher levels of ISP. Hypercholesterolemia (> or =6.5 mmol/L, 251 mg/dL) was associated with an increased incidence of ischemic stroke and cardiac events and with a reduced incidence of intracerebral hemorrhage. The ISP levels modified these associations. After risk factor adjustment, men with hypercholesterolemia and high ISP levels had a significantly higher risk of cardiovascular death (relative risk [RR]=2.4; CI, 1.8 to 3.3), cardiac events (RR=2.3; CI, 1.8 to 3.0), and ischemic stroke (RR=2.1; CI, 1.4 to 3.3) than men with normal cholesterol and low ISP levels. In the absence of high ISP levels, hypercholesterolemia was associated with a moderately higher risk of cardiovascular death (RR=1.4; CI, 1.0 to 2.0) and cardiac events (RR=1.5; CI, 1.2 to 1.9) but not significantly with ischemic stroke (RR=1.25; CI, 0.8 to 2.0). CONCLUSIONS: Hypercholesterolemia is associated with high plasma levels of ISP. These proteins increase the cholesterol-related incidence of cardiovascular diseases. In the absence of elevated ISP levels, no statistically confirmed association was found between hypercholesterolemia and ischemic stroke.

The enigma of increased non-cancer mortality after weight loss in healthy men who are overweight or obese.

OBJECTIVE: To study effects on non-cancer mortality of observational weight loss in middle-aged men stratified for body mass index (BMI), taking a wide range of possible confounders into account. DESIGN: Prospective, population based study. SETTING: Male population of Malmö, Sweden. PARTICIPANTS: In all 5722 men were screened twice with a mean time interval of 6 years in Malmö, southern Sweden. They were classified according to BMI category at baseline (<21, 22-25, overweight: 26-30, and obesity: 30+ kg m(-2)) and weight change category until second screening (weight stable men defined as having a baseline BMI +/- 0.1 kg m(-2) year-1 at follow-up re-screening). MAIN OUTCOME MEASURES: Non-cancer mortality calculated from national registers during 16 years of follow-up after the second screening. Data from the first year of follow-up were excluded to avoid bias by mortality caused by subclinical disease at re-screening. RESULTS: The relative risk (RR; 95% CI) for non-cancer mortality during follow-up was higher in men with decreasing BMI in all subgroups: RR 2.64 (1.46-4.71, baseline BMI <21 kg m(-2)), 1.39 (0.98-1.95, baseline BMI 22-25 kg m(-2)), and 1.71 (1.18-2.47, baseline BMI 26+ kg m(-2)), using BMI-stable men as reference group. Correspondingly, the non-cancer mortality was also higher in men with increasing BMI, but only in the obese group (baseline BMI 26+ kg m(-2)) with RR 1.86 (1.31-2.65). In a subanalysis, nonsmoking obese (30+ kg m(-2)) men with decreased BMI had an increased non-cancer mortality compared with BMI-stable obese men (Fischer's test: P=0.001). The mortality risk for nonsmoking overweight men who increased their BMI compared with BMI-stable men was also significant (P=0.006), but not in corresponding obese men (P=0.094). CONCLUSIONS. Weight loss in self-reported healthy but overweight middle-aged men, without serious disease, is associated with an increased non-cancer mortality, which seems even more pronounced in obese, nonsmoking men, as compared with corresponding but weight-stable men. The explanation for these observational findings is still enigmatic but could hypothetically be because of premature ageing effects causing so-called weight loss of involution.

Interleukin-1 receptor antagonist is detectable in human carotid artery plaques and is related to triglyceride levels and Chlamydia pneumoniae IgA antibodies.

OBJECTIVES: To investigate whether the interleukin-1 receptor antagonist (Il-1ra) and interleukin-1beta (Il-1beta) can be detected in human carotid artery tissue, and whether their presence is related to evidence of Chlamydia pneumoniae infection, risk factors for atherosclerosis, and clinical data. SETTING: Departments of Vascular Diseases and Surgical Pathophysiology, University Hospital, Malmö, Sweden. SUBJECTS: A total of 66 patients undergoing carotid endarterectomy (median age 74, range 53-89 years, 26 women). Il-1beta and Il-1ra were studied in carotid artery plaques and in Il-1ra in serum. RESULTS: Interleukin-1 receptor antagonist was detected in mononuclear cells in plaques from 37/66 (56%) patients. Patients with Il-1ra in plaques showed higher [2.04 (1.70-3.14) mmol x L(-1) vs. 1.69 (1.09-1.99) mmol x L(-1); P < 0.05] serum(s-)triglyceride(tg) levels, and a higher frequency of IgA seropositivity for C. pneumoniae (76% vs. 52%; P < 0.05) than those without. S-Il-1ra levels correlated with s-tg levels (r=0.38; P=0.047). There were no differences between patients with and without Il-1ra in plaques concerning s-Il-1ra, blood(b-)haemoglobin or leucocyte count, s-cholesterol, b-glucose, blood pressure, IgG seropositivity for C. pneumoniae, prevalence of neurological symptoms preceding operation, smoking, or diabetes mellitus. There were no differences in frequency of Il-1ra in plaques or in s-Il-1ra levels between patients with symptomatic and asymptomatic stenosis, between smokers and nonsmokers, or between diabetic and nondiabetic patients. Il-1beta was not detected in plaques in the current study. CONCLUSION: Interleukin-1 receptor antagonist can be detected in human atherosclerotic carotid artery plaques, and is related to s-triglyceride levels and IgA seropositivity for C. pneumoniae, but not to prevalence of neurological symptoms related to embolization.

Predictors of carotid endarterectomy in middle-aged individuals.

The objective was to investigate which screening variables in a population study predicted carotid endarterectomy. Among 793 carotid endarterectomies performed at Malmö University Hospital between 1991 and 1998, 85 patients (14 females) were identified that had participated in a population screening between 1974 and 1991. Median time from screening to operation was 16 years (range 6-26 years). Screening variables were compared with corresponding values from the background screening population (n = 33261). As operated patients were older than the background population at screening (49 [37-60] vs. 46 [26-61] years; p < 0.0001), comparisons were age-adjusted. Operated patients had higher systolic blood pressure (SBP; 130 [126-133] vs. 125 [125-125] mmHg; p < 0.01), serum total cholesterol (6.1 [5.9-6.3] vs. 5.7 [5.7-5.7] mmol/l; p < 0.0001), serum triglyceride (1.4 [1.3-1.6] vs. 1.1 [1.1-1.1] mmol/l; p < 0.0001), serum glutamic acid transferase (0.46 [0.40-0.53] vs. 0.40 [0.40-0.41] microkat/l; p < 0.05), and plasma fibrinogen (3.77 [3.42-4.16] vs. 3.35 [3.30-3.41] mmol/l; p < 0.05) levels, a lower 120-min insulin/glucose ratio at an oral glucose tolerance test (OGTT; 0.48 [0.38-0.58] vs. 0.60 [0.59-0.61]; p < 0.05) and forced vital lung capacity (3.7 [3.6-3.9] vs. 3.9 [3.9-4.0] l/min; p < 0.05), and a higher prevalence of smoking at screening (68% vs. 45%; p < 0.0001). Smoking, SBP, serum total cholesterol, and the 120-min insulin/glucose ratio remained independent predictors for carotid surgery in multivariate analysis. No differences existed among patients operated on because of symptomatic and asymptomatic stenosis. In conclusion, increased SBP and total cholesterol, lower 2-h insulin/glucose ratio at an OGTT, and smoking predict carotid surgery at long-term follow-up.

Influence of plasma fibrinogen levels on the incidence of myocardial infarction and death is modified by other inflammation-sensitive proteins: a long-term cohort study.

Inflammation may play an important role in atherosclerotic disease. Plasma fibrinogen is an established predictor of cardiovascular events. The aim of this study was to evaluate whether other inflammation-sensitive plasma proteins modify this prediction. We studied the incidence of cardiac events and death in men in relation to fibrinogen levels alone and in combination with other proteins. The study was based on 6075 men, who were, on average, 46 years old at the time of the screening examination, which included the quantitative assessment of plasma levels of fibrinogen, orosomucoid, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin. The concentration of each protein was divided into quartiles for each. This classification made it possible to identify 4 groups, ie, men in the first fibrinogen quartile and at the same time either not belonging to the fourth quartile of any of the other proteins (Q1/No group) or also belonging to the fourth quartile of >/=1 of the additional proteins (Q1/Yes group) and corresponding groups in the fourth fibrinogen quartile (Q4/No and Q4/Yes groups). During the follow-up, which occurred at an average of 16 years, 439 (7.2%) men experienced a cardiac event, and 653 (10.7%) died; 278 of these men died of cardiovascular diseases, with 206 deaths attributed to ischemic heart disease. From the lowest to the highest quartile, there was for each protein a stepwise increase in the incidence of cardiac events and mortality. All-cause mortality and cardiovascular mortality were significantly higher in the Q4/Yes group compared with the Q4/No group, but they were similar in the Q4/No and Q1/Yes groups. The incidence of cardiac events was significantly higher in the Q1/Yes and Q4/Yes groups compared with the Q1/No and Q4/No groups, respectively. The increased cardiovascular mortality and cardiac event rates remained after adjustment for several confounders when the Q4/Yes and Q4/No groups were compared. The results suggest that the incidence of cardiac events and death due to cardiovascular diseases in middle-aged men predicted by plasma levels of fibrinogen is modified by other inflammation-sensitive proteins.

Overweight is associated with lower serum leptin in Peruvian Indian than in Caucasian women: A dissociation contributing to low blood pressure?

We tested whether plasma levels of leptin and insulin are associated with the lower blood pressure in women of Peruvian Indian heritage compared with Caucasian women. A total of 181 women from Peru and 85 from Sweden, aged 20 to 60 years, with normal plasma glucose levels participated in the study. Measurements of anthropometry, blood pressure, and blood tests were performed after overnight fasting. Compared with women from Umeå in Sweden, women from Lima, Peru had higher body mass index (BMI) (26.2 +/- 4.9 v 24.4 +/- 3.8 kg/m(2)), waist circumference (85 +/- 11 v 79 +/- 10 cm), lower systolic blood pressure (99 +/- 15 v 114 +/- 14 mm; P <.001) and diastolic blood pressure (67 +/- 7 v 74 +/- 10 mm; P <.001). In addition, they had a reduction of the ratio of plasma leptin to BMI (0.52 +/- 0.22 v 0.61 +/- 0.36; P <.001), greater plasma insulin (80 +/- 42 v 41 +/- 21 pmol/L), but lower plasma glucose (4.2 +/- 0.5 v 5.1 +/- 0.5 mmol/L; P <.001). Furthermore, the 181 women from Lima had higher plasma triglyceride levels (1.5 +/- 0.8 v 1.3 +/- 0.7; P =.039), but lower plasma high-density lipoprotein (HDL)-cholesterol (1.0 +/- 0.2 v 1.5 +/- 0.4 mmol/L; P <.001) and total plasma cholesterol (5.0 +/- 1.1 v 5.9 +/- 1.3 mmol/L; P <.001) levels. Plasma leptin correlated with blood pressure and BMI in both populations (P <.001). In multiple regression analysis, BMI, but not log leptin, emerged as the determinant for systolic blood pressure. We concluded that women living in Lima have significant lower blood pressure levels in association with elevated plasma insulin concentrations, but lower plasma leptin values adjusted for BMI in comparison with women from northern Sweden. This may suggest that the concept of metabolic syndrome is different among women with Peruvian Indian heritage in comparison to a Caucasian population.

Prediction of diabetes using ADA or WHO criteria in post-menopausal women: a 10-year follow-up study.

AIMS/HYPOTHESIS: To study the risk of women with impaired fasting glucose (IFG) as against impaired glucose tolerance (IGT) developing diabetes. METHODS: Oral glucose tolerance tests (75 g) were done in 265 women selected at random at baseline (age 55-57 years) and at a 10-year follow-up. Of the women 42 had IFG/NGT (fasting glucose 6.1-6.9 mmol/l, 2-h glucose < 7.8 mmol/l), 66 IGT/ NFG (2-h glucose 7.8-11.0 mmol/l, fasting glucose < 6.1 mmol/1), 30 IGT/IFG and 127 NFG/NGT. RESULTS: The 10-year progression to diabetes was similar in IGT/NFG (12.1%) and IFG/NGT groups (11.9%, p = 0.97). In IGT/IFG, 20.0% had developed diabetes, which was not significantly higher than in IFG/NGT and IGT/NFG (p = 0.53). In NFG/ NGT at baseline, only 3.9 % had developed diabetes, which was lower than in the other groups (p = 0.023). CONCLUSION/INTERPRETATION: Fasting and 2-h glucose concentrations are equally good in predicting diabetes development over a 10-year period in Caucasian postmenopausal women. Because IGT is more common than IFG, measuring only fasting glucose concentrations would, however, result in missing a prediabetic stage in a large group of people at risk for diabetes and cardiovascular diseases.

The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study.

OBJECTIVE: To assess the effect of orlistat on body weight and cardiovascular risk amongst obese patients at high coronary risk. DESIGN: After screening, patients entered a two-week single-blind placebo lead-in period, during which they followed a mildly hypocaloric diet, before being randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with dietary intervention for 1 years. SETTING: The study was conducted at 33 primary care centres in Sweden. SUBJECTS: A total of 382 obese adults (body mass index 28-38 kg m-2) with type 2 diabetes, hypercholesterolaemia and/or hypertension were recruited, of whom 376 were randomized to orlistat (n = 190) or placebo (n = 186). MAIN OUTCOME MEASURES: Change in body weight, waist and hip circumferences, blood pressure, serum lipid profile, fasting glucose and HbA1c. RESULTS: After 1 years, mean weight loss was significantly greater with orlistat compared with placebo (5.9% vs. 4.6%; P < 0.05). Moreover, significantly more orlistat-treated patients than placebo recipients maintained weight loss of > or = 5% (54.2% vs. 40.9%; P < 0.001). Orlistat was also associated with significantly greater improvements than placebo in total serum cholesterol (- 3.3% vs. -0.5%; P < 0.05), LDL-cholesterol (- 7.0% vs. -1.1%; P < 0.05), fasting glucose (5.1% vs. -0.1%; P < 0.01) and HbA1c (- 2.7% vs. -0.5%; P < 0.05). Similar results were reported for the subgroup of patients with type 2 diabetes. Orlistat was well tolerated. CONCLUSIONS: Treatment with orlistat in conjunction with diet promotes significantly greater weight loss and cardiovascular risk factor reduction than diet alone amongst obese patients at high risk of future coronary events.

Increased plasma endothelin-1 and intraplatelet cyclic guanosine monophosphate in men with disturbed glucose metabolism.

Plasma endothelin-1, the nitric oxide (NO) mediator intraplatelet cyclic guanosine monophosphate (cGMP), the prostacyclin mediator cyclic adenosine monophosphate (cAMP) and the macrophage derived inflammatory mediator plasma neopterin were measured in men with Type 2 diabetes mellitus (n=91), impaired glucose tolerance (IGT; n=51), previously abnormal glucose tolerance (PAGT; n=20), and 34 healthy control men. Plasma endothelin-1was higher in men with Type 2 diabetes mellitus than in controls [4.1 (1.0-14.3) vs. 2.1 (0.2-8. 7) ng/l; P<0.001). Intraplatelet cGMP was higher in men with PAGT [0. 84 (0.57-2.76) pmol/10(9) platelets; P<0.05], IGT [0.85 (0.48-3.53); P<0.001] and Type 2 diabetes mellitus [0.90 (0.47-3.86); P<0.001] than in controls [0.70 (0.42-1.70]. No differences existed between groups concerning intraplatelet cAMP or plasma neopterin. Plasma endothelin-1 correlated with fasting plasma glucose (r=0.33; P<0.001) and HbA1(c) (r=0.29; P<0.001). In conclusion, elevated plasma endothelin-1 in Type 2 diabetes mellitus and its relationship to glucose and HbA1(c) suggest a putative role for endothelin-1 in diabetic endothelial cell damage. Increased cGMP indicating enhanced production/activity of NO suggests that factors other than reduced NO activity contribute to enhanced platelet aggregation in diabetes.