Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials.

OBJECTIVES: In the Norwegian Vitamin Trial and the Western Norway B Vitamin Intervention Trial, patients were randomly assigned to homocysteine-lowering B-vitamins or no such treatment. We investigated their effects on cardiovascular outcomes in the trial populations combined, during the trials and during an extended follow-up, and performed exploratory analyses to determine the usefulness of homocysteine as a predictor of cardiovascular outcomes. DESIGN: Pooling of data from two randomized controlled trials (1998-2005) with extended post-trial observational follow-up until 1 January 2008. SETTING: Thirty-six hospitals in Norway. SUBJECTS: 6837 patients with ischaemic heart disease. INTERVENTIONS: One capsule per day containing folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg), or folic acid plus vitamin B12, or vitamin B6 alone or placebo. MAIN OUTCOME MEASURES: Major adverse cardiovascular events (MACEs; cardiovascular death, acute myocardial infarction or stroke) during the trials and cardiovascular mortality during the extended follow-up. RESULTS: Folic acid plus vitamin B12 treatment lowered homocysteine levels by 25% but did not influence MACE incidence (hazard ratio, 1.07; 95% CI, 0.95-1.21) during 39 months of follow-up, or cardiovascular mortality (hazard ratio, 1.12; 95% CI, 0.95-1.31) during 78 months of follow-up, when compared to no such treatment. Baseline homocysteine level was not independently associated with study outcomes. However, homocysteine concentration measured after 1-2 months of folic acid plus vitamin B12 treatment was a strong predictor of MACEs. CONCLUSION: We found no short- or long-term benefit of folic acid plus vitamin B12 on cardiovascular outcomes in patients with ischaemic heart disease. Our data suggest that cardiovascular risk prediction by plasma total homocysteine concentration may be confined to the homocysteine fraction that does not respond to B-vitamins.

Low testosterone levels are associated with carotid atherosclerosis in men.

OBJECTIVE: To study the relationship between endogenous sex hormone levels and intima-media thickness (IMT) of the carotid artery measured by ultrasonography. DESIGN: Population-based cross-sectional study. METHODS: Sex hormone levels measured by immunoassay, anthropometric measurements and IMT was studied in 1482 men aged 25-84 years participating in the 1994-1995 Tromsø study. The data were analysed with partial correlation, multiple linear regression and logistic regression analysis. RESULTS: Linear regression models showed that total testosterone and sex hormone-binding globulin levels, but not calculated free testosterone, serum oestradiol or dehydroepiandrosterone sulphate levels were inversely associated with the age-adjusted IMT (P = 0.008 and P < 0.001 respectively). These associations were independent of smoking, physical activity, blood pressure and lipid levels, but were not independent of body mass index (BMI). Excluding men with cardiovascular disease (CVD) did not materially change these results. In a logistic regression model adjusted for the confounding effect of CVD risk factors, men with testosterone levels in the lowest quintile (<9.0 nmol L(-1)) had an independent OR = 1.51 (P = 0.015) of being in the highest IMT quintile. CONCLUSIONS: We found an inverse association between total testosterone levels and IMT of the carotid artery in men that was present also after excluding men with CVD, but was not independent of BMI. The clinical relevance of this, however, is uncertain and needs to be investigated in a clinical setting.

Reduced neuropsychological test performance in asymptomatic carotid stenosis: The Tromsø Study.

OBJECTIVE: To assess the relationship between asymptomatic carotid stenosis, neuropsychological test performance, and silent MRI lesions. METHODS: Performance on several neuropsychological tests was compared in 189 subjects with ultrasound-assessed carotid stenosis and 201 control subjects without carotid stenosis, recruited from a population health study. Subjects with a previous history of stroke were excluded. The test battery included tests of attention, psychomotor speed, memory, language, speed of information processing, motor functioning, intelligence, and depression. Sagittal T1-weighted and axial and coronal T2-weighted spin echo MRI was performed, and presence of MRI lesions (white matter hyperintensities, lacunar and cortical infarcts) was recorded. RESULTS: Subjects with carotid stenosis had significantly lower levels of performance in tests of attention, psychomotor speed, memory, and motor functioning, independent of MRI lesions. There were no significant differences in tests of speed of information processing, word association, or depression. Cortical infarcts and white matter hyperintensities were equally distributed among persons with and without carotid stenosis. Lacunar infarcts were more frequent in the stenosis group (p = 0.03). CONCLUSIONS: Carotid stenosis was associated with poorer neuropsychological performance. This could not be explained by a higher proportion of silent MRI lesions in persons with asymptomatic carotid stenosis, making it less likely that the cognitive impairment was caused by silent emboli.

Intra- and interobserver variability in the measurements of abdominal aortic and common iliac artery diameter with computed tomography. The Tromsø study.

OBJECTIVES: to assess intra- and interobserver variability in the measurement of aortic and common iliac artery diameter by means of computed tomography (CT). DESIGN: reproducibility study. MATERIAL AND METHODS: three radiologists performed measurements of aortic diameter at five different levels and of both common iliac arteries with CT. Fifty-nine subjects were examined, 29 with and 30 without abdominal aortic aneurysms (AAA) as assessed by ultrasound. RESULTS: intraobserver variability varied between radiologists, measurement plane (anterior-posterior vs transverse) and measurement level. The interobserver variability was markedly higher at the bifurcation than at the suprarenal level and higher than intraobserver variability for measurements at all levels. Both intraobserver and interobserver variability increased with increasing vessel diameter and were largest in patients with AAA. The absolute intraobserver difference of the maximal infrarenal aortic diameter was 2mm or less in 94% of intraobserver pairs. The corresponding interobserver difference was 82%. CONCLUSIONS: interobserver variability of CT measurements of aortic and common iliac artery diameter is not negligible and should be taken into account when making clinical decisions. When assessing change in aortic diameter, previous CT-scans should be reviewed simultaneously as a routine to exclude interobserver variability.

Low levels of high-density lipoprotein cholesterol are associated with echolucent carotid artery plaques: the tromsø study.

BACKGROUND AND PURPOSE: Ultrasound-assessed plaque morphology is an independent predictor of ischemic stroke. The purpose of this population-based cross-sectional nested case-control study was to examine the risk factors associated with carotid plaque morphology. METHODS: Ultrasonography of the right carotid artery was conducted on 6727 participants in a population health survey (response rate 79%). Plaque echogenicity, defined as reflectance of the emitted ultrasound signal, was scored as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. Information on cardiovascular risk factors in all 216 participants who had carotid stenosis and in 223 control subjects matched by age and sex who did not have carotid stenosis was obtained from measurements of blood pressure, weight, height, and nonfasting blood samples and from a self-administered questionnaire. RESULTS: In both univariate and multivariate analyses, low levels of HDL cholesterol and increasing degree of stenosis were independently associated with an increased risk of having an echolucent plaque. For 1-SD increase in HDL cholesterol, the adjusted odds of being in a lower plaque echogenicity category decreased by approximately 30% (OR 0.69, 95% CI 0.52 to 0.93). CONCLUSIONS: These findings indicate that low levels of HDL cholesterol are associated with an increased risk of having echolucent, rupture-prone atherosclerotic plaques.

Prevalence of and risk factors for abdominal aortic aneurysms in a population-based study : The Tromsø Study.

In a population-based study of 6,386 men and women aged 25--84 years in Tromsø, Norway, in 1994--1995, the authors assessed the age- and sex-specific distribution of the abdominal aortic diameter and the prevalence of and risk factors for abdominal aortic aneurysm. Renal and infrarenal aortic diameters were measured with ultrasound. The mean infrarenal aortic diameter increased with age. The increase was more pronounced in men than in women. The age-related increase in the median diameter was less than that in the mean diameter. An aneurysm was present in 263 (8.9%) men and 74 (2.2%) women (p < 0.001). The prevalence of abdominal aortic aneurysm increased with age. No person aged less than 48 years was found with an abdominal aortic aneurysm. Persons who had smoked for more than 40 years had an odds ratio of 8.0 for abdominal aortic aneurysm (95% confidence interval: 5.0, 12.6) compared with never smokers. Low serum high density lipoprotein cholesterol was associated with an increased risk for abdominal aortic aneurysm. Other factors associated with abdominal aortic aneurysm were a high level of plasma fibrinogen and a low blood platelet count. Antihypertensive medication (ever use) was significantly associated with abdominal aortic aneurysm, but high systolic blood pressure was a risk factor in women only. This study indicates that risk factors for atherosclerosis are also associated with increased risk for abdominal aortic aneurysm.

Prevalence of and risk factors associated with carotid artery stenosis: the Tromsø Study.

BACKGROUND AND PURPOSE: To assess prevalence, distribution, ultrasound characteristics and determinants of carotid artery stenosis in a large, population-based study of both women and men. METHODS: A total of 6,727 persons aged 25-84 years were screened for extracranial stenosis with Duplex ultrasound of the right carotid artery. Risk factors were compared in 225 persons with stenosis and 5,514 persons without. RESULTS: The prevalence of carotid stenosis was higher in men than in women, where 3.8% (95% CI, 3.2-4.6%) had carotid stenosis, compared to 2.7% (95% CI, 2.2-3.3%) in women (p = 0.001). The prevalence gradually increased by age in both genders. Cholesterol, HDL cholesterol, fibrinogen, systolic blood pressure levels and current smoking were independently associated with carotid artery stenosis in both women and men. The presence of carotid stenosis was significantly associated with a history of cerebrovascular disease, coronary heart disease and peripheral artery disease. For each 10% increase in the degree of carotid stenosis, the risk of having had a cerebrovascular event increased by 26%. CONCLUSIONS: The prevalence of carotid stenosis in the general population, as measured by ultrasound, is low. Age, male gender, smoking, total cholesterol, HDL cholesterol (inverse), fibrinogen and systolic blood pressure are all independent predictors of carotid artery stenosis.

Echolucent plaques are associated with high risk of ischemic cerebrovascular events in carotid stenosis: the tromsø study.

BACKGROUND: The purpose of the study was to assess in a prospective design whether plaque morphology is associated with risk of ischemic stroke and other cerebrovascular events in subjects with carotid stenosis. METHODS AND RESULTS: A total of 223 subjects with carotid stenosis (123 with 35% to 49% degree of stenosis, 100 with 50% to 99% stenosis) and 215 control subjects matched by age and sex who participated in a population health survey at baseline were followed up for 3 years. Plaque echogenicity was assessed by ultrasound at baseline and scored as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. Forty-four subjects experienced >/=1 ischemic cerebrovascular events in the follow-up period. Plaque echogenicity, degree of stenosis, and white blood cell count were independent predictors of cerebrovascular events. The unadjusted relative risk for cerebrovascular events was 13.0 (95% CI 4.5 to 37.4) in subjects with echolucent plaques and 3.7 (95% CI 0.7 to 18.2) in subjects with echogenic plaques when subjects without stenosis were used as the reference. The adjusted relative risk for cerebrovascular events in subjects with echolucent plaques was 4.6 (95% CI 1.1 to 18.9), and there was a significant linear trend (P=0.015) for higher risk with increasing plaque echolucency. The adjusted relative risk for a 10% increase in the degree of stenosis was 1.2 (95% CI 1.04 to 1.4). CONCLUSIONS: Subjects with echolucent atherosclerotic plaques have increased risk of ischemic cerebrovascular events independent of degree of stenosis and cardiovascular risk factors. Subjects at high risk for ischemic vascular events may be identified by ultrasound assessment of plaque morphology.

Serum lipids and regulation of tissue factor-induced coagulation in middle-aged men.

Formation of an occlusive thrombus by exposure of tissue factor (TF) to circulating blood and subsequent triggering of coagulation by TF-activated factor VII (FVIIa) complexes on ruptured atherosclerotic plaques is thought to be a key event in myocardial infarction. Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of TF-induced coagulation in which the anticoagulant function most probably is restricted to free TFPI in human plasma. The present study was undertaken to assess the interrelations between serum lipids and components of TF-induced coagulation in 234 apparently healthy men aged 36-56 years recruited from the general population. Plasma free TFPI antigen (Ag) was positively correlated (P < .001) with total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B (apoB-100), fibrinogen, total amount of FVII (FVIIam), coagulation activity of factor VII (FVIIc), and FVIIa. The significant predictors for free TFPI Ag were total cholesterol, triglycerides, fibrinogen, FVIIc, and age, which explained 33% of the plasma variation in free TFPI Ag assessed by multiple regression analysis. A highly significant (P < .0001) linear trend for increase in atherogenic lipids (i.e., total cholesterol and triglycerides), FVII (i.e., FVIIc and FVIIa), and fibrinogen across quartiles of TFPI Ag was demonstrated after adjustment for confounders. These findings may indicate a compensatory increase in plasma free TFPI with lipid and hemostatic risk factors for atherothrombotic diseases in healthy middle-aged men.

Age and sex differences in the relationship between inherited and lifestyle risk factors and subclinical carotid atherosclerosis: the Tromsø study.

BACKGROUND: Ultrasound measurement of carotid artery intima-media thickness (IMT) is regarded as a valid index of atherosclerosis. Age and sex differences in the distribution of, and risk factors for, IMT have not been investigated thoroughly. METHODS: In 1994-1995 a total of 6408 men and women aged 25-84 years living in the municipality of Tromsø, Norway, underwent ultrasound examination of carotid artery IMT and measurements of cardiovascular risk factors. RESULTS: Age, systolic blood pressure, total cholesterol, HDL cholesterol, body mass index, and smoking were independent predictors of IMT in both sexes. Fibrinogen levels and physical activity were associated with IMT in men only, whereas triglyceride levels were associated with IMT independently of HDL cholesterol in women only. A family history of cardiovascular disease (CVD) was an independent predictor of IMT in both sexes, also when controlling for traditional CVD risk factors. The magnitude of the association between most risk factors and IMT did not differ depending on age, but the effects of physical activity and triglycerides were more pronounced at higher age. CONCLUSION: These data suggest that there are significant age and sex differences in the distribution and the determinants of subclinical atherosclerosis.

Determinants of serum calcium in men and women. The Tromsø Study.

The level of serum calcium appears to be associated with blood pressure and metabolic risk factors for cardiovascular disease. Determinants of serum calcium may therefore be of interest. In a health survey in Tromsø in 1994-1995, 27,159 subjects were examined. The survey included measurements of serum calcium and questionnaires on diet and lifestyle factors. In males mean serum calcium declined from 2.41 mmol/l for those in their 20s to 2.34 mmol/l for those in their 80s. In females mean serum calcium was stable at a level of 2.35 mmol/l before the menopause, and thereafter reached a plateau of 2.39 mmol/l. In both sexes serum calcium showed a positive association with body mass index (BMI) and coffee consumption that persisted after correcting for other variables in a multiple regression model (p < 0.05). Physical activity had no significant association with serum calcium. In females alcohol consumption was negatively, and cigarette smoking positively associated with serum calcium (p < 0.01). No significant effect on the serum calcium levels was found for the intake of calcium or vitamin D, except for males with a calcium intake below 200 mg/day. Some of the observed effects, like the variation with age, may partly be explained by alterations in levels of serum albumin to which approximately 40% of circulating calcium is bound and which was not adjusted for in this study, whereas that is hardly the case for the association with BMI and coffee consumption. However, none of these factors could affect the serum calcium level more than 0.02 mmol/l, and the biological significance of the observed associations questionable.

Primary hyperparathyroidism detected in a health screening. The Trømsø study.

Serum calcium was measured in 12,339 men and 13,394 women ages 25 to 75. Primary hyperparathyroidism, defined as a combination of serum calcium and parathyroid hormone (PTH) levels within the extreme or upper normal range, was diagnosed in 17 men and 47 women. The prevalence in both sexes increased with age. When 42 subjects with asymptomatic primary hyperparathyroidism were followed for 3 years, no significant increase in serum calcium or PTH was seen. In a subgroup of 473 men and 517 women ages 50 to 75, serum PTH was measured along with serum calcium. Depending on the criteria used to define primary hyperparathyroidism, the prevalence in older women within this subgroup ranged from 3.6% to 13.9%. The study concluded that a high prevalence of primary hyperparathyroidism exists in older women, although the progression of the disease, judging by serum calcium and PTH measurements, appears to be very slow.

Fatty acid chain length and degree of unsaturation are inversely associated with serum triglycerides.

Little is known about the association between dietary fatty acids and serum triglycericle concentrations. Plasma fatty acids may reflect dietary intake and can be used to study the relationship between concentrations of individual fatty acids and serum lipids. We examined the cross-sectional relationship of plasma fatty acids with serum nonfasting triglyceride and total cholesterol concentrations. Relative concentrations of individual plasma phospholipid fatty acids were determined by gas liquid chromatography among 4,158 men aged 40-42 yr, who participated in a population study. The pattern of associations between individual fatty acids and cholesterol was different from that between individual fatty acids and triglyceride concentrations. All fatty acids displayed positive associations with total cholesterol concentration except linoleic acid, which was inversely related to cholesterol. In contrast, associations between individual fatty acids and triglyceride concentrations differed in strength and direction depending on both carbon chain length and the degree of unsaturation. Concentrations of very long chain (20 carbon atoms or more) saturated, monounsaturated, and n-3 polyunsaturated fatty acids showed significant inverse associations with triglycerides, whereas shorter fatty acids within these classes were positively associated with triglyceride concentrations. The present data suggest that the associations between concentrations of serum triglycerides and plasma phospholipid fatty acids depend on both fatty acid chain length and the degree of unsaturation.

Prediction of mortality by ultrasound screening of a general population for carotid stenosis: the Tromsø Study.

BACKGROUND AND PURPOSE: The extensive use of ultrasound examination of carotid arteries has revealed stenosis in many asymptomatic subjects, and clinical studies have shown that carotid stenosis is a risk factor for cardiovascular disease and death. However, information on stenosis as detected in a general population and its relation to mortality is scarce. The purpose of this population-based study was to assess whether carotid stenosis is a predictor of death. METHODS: In 1994 to 1995, 248 subjects with suspected carotid stenosis were identified among 6727 men and women 25 to 84 years of age who were examined with ultrasound. These subjects and 496 age- and sex-matched control subjects were followed up for 4.2 years, and the number and causes of deaths were registered. RESULTS: The unadjusted relative risk for death was 2.72 (95% CI, 1.57 to 4.75) for subjects with stenosis compared with control subjects. Adjusting for cardiovascular risk factors increased the relative risk to 3.47 (95% CI, 1.47 to 8.19). The adjusted relative risk in persons with stenosis and no cardiovascular disease or diabetes was 5.66 (95% CI, 1.53 to 20.90), which was higher than in subjects with stenosis and self-reported disease (1.79; 95% CI, 0.75 to 4.27). There was a dose-response relationship between degree of stenosis and risk of death (P=0.002 for linear trend). Carotid stenosis was a stronger predictor of death than self-reported cardiovascular disease or diabetes. CONCLUSIONS: Carotid stenosis is a strong and independent predictor of death.

Cost and health consequences of reducing the population intake of salt.

STUDY OBJECTIVE: The aim was to estimate health and economic consequences of interventions aimed at reducing the daily intake of salt (sodium chloride) by 6 g per person in the Norwegian population. Health promotion (information campaigns), development of new industry food recipes, declaration of salt content in food and taxes on salty food/subsidies of products with less salt, were possible interventions. DESIGN: The study was a simulation model based on present age and sex specific mortality in Norway and estimated impact of blood pressure reductions on the risks of myocardial infarction and stroke as observed in Norwegian follow up studies. A reduction of 2 mm Hg systolic blood pressure (range 1-4) was assumed through the actual interventions. The cost of the interventions in themselves, welfare losses from taxation of salty food/subsidising of food products with little salt, cost of avoided myocardial infarction and stroke treatment, cost of avoided antihypertensive treatment, hospital costs in additional life years and productivity gains from reduced morbidity and mortality were included. RESULTS: The estimated increase in life expectancy was 1.8 months in men and 1.4 in women. The net discounted (5%) cost of the interventions was minus $118 millions (that is, cost saving) in the base case. Sensitivity analyses indicate that the interventions would be cost saving unless the systolic blood pressure reduction were less than 2 mm Hg, productivity gains were disregarded or the welfare losses from price interventions were high. CONCLUSION: Population interventions to reduce the intake of salt are likely to improve the population's health and save costs to society.

Validity of self-reported stroke : The Tromso Study.

BACKGROUND AND PURPOSE: The aim of this study was to validate the diagnosis of self-reported stroke. METHODS: During 1994-1995, 27 159 people attended a population health survey in the community of Tromso, Norway, a response rate of 77%. A total of 418 attenders reported a history of stroke. In 1997, all individuals with a self-reported stroke who were still living in the community (n=362) were invited to a clinical reexamination. For each of the 269 people who were reexamined, a person who reported no history of stroke was selected and was reexamined in the same way. RESULTS: On the basis of the reexamination, 213 (79.2%) of the self-reported strokes were confirmed. Thirteen individuals (4.8%) had a possible stroke. The remaining 43 individuals had either transient ischemic attack (TIA; n=18), traumatic head injuries (n=16), or perinatal cerebral damage, complicated migraine, syncope, possible TIA, or cerebral aneurysm without bleeding (n=9). Among the confirmed strokes, 30 (14.1%) were hemorrhagic and 118 (55.4%) were thromboembolic. Of the 30 hemorrhages, 16 were subarachnoidal bleedings, 10 due to ruptured aneurysms. The histories of stroke, including both the symptoms and the signs, often had a paucity of details and precision, making it impossible to classify 65 stroke victims (30.5%) into stroke subtypes. The positive predictive value (PPV) of a self-reported stroke was 0.79. The PPV was significantly (P=0.016) greater in men (0.88) than in women (0.73). Individuals older than 60 years had a significantly greater PPV than those younger than 60 years (PPV 0.83 and 0.73, respectively; P=0.05). Hypertension was associated with a greater PPV, whereas a history of either ischemic heart disease, diabetes mellitus, lung disease, or depression had no impact on the PPV. The estimated sensitivity of self-reported stroke in the survey population was approximately 80% and the specificity was 99%. CONCLUSIONS: We conclude that a self-administered questionnaire can be used to assess the prevalence of stroke in epidemiological research.

Calcium from dairy products, vitamin D intake, and blood pressure: the Tromso Study.

BACKGROUND: The present epidemiologic study was conducted in Tromso, Northern Norway, in 1994-1995. OBJECTIVE: The objective was to evaluate the relation between calcium intake from dairy products and the intake of vitamin D on systolic and diastolic blood pressure. DESIGN: Subjects who were taking drugs for hypertension or heart disease, those taking calcium tablets, subjects reporting cardiovascular disease, and pregnant women were excluded, leaving 7543 men and 8053 women aged 25-69 y for analysis. Calcium and vitamin D intakes were calculated from a food-frequency questionnaire. RESULTS: After correction for age, body mass index, alcohol and coffee consumption, physical activity, cigarette smoking, and vitamin D intake, there was a significant linear decrease in systolic and diastolic blood pressure with increasing dairy calcium intake in both sexes (P < 0.05). However, the difference in blood pressure between subjects with the highest and those with the lowest calcium intake was

Relation between low calcium intake, parathyroid hormone, and blood pressure.

In a population health survey in 1995, serum parathyroid hormone (PTH) was measured in 1113 subjects, aged 30 to 79 years, and was found to be elevated (>6.9 pmol/L) in 118 subjects. In 1998, this group and 131 subjects with normal PTH levels were invited for reexamination, and 82 and 90 subjects from each respective group attended the follow-up. At the follow-up, 72 subjects had elevated and 100 had normal serum PTH levels. Those with elevated serum PTH levels (8 subjects with hyperparathyroidism were excluded) had significantly lower serum calcium levels and intake of calcium than those with normal PTH (2.24+/-0.09 and 2.29+/-0.10 mmol/L [mean+/-SD] and 400.3+/-227.3 and 592.1+/-459.6 mg/d, respectively; P<0.01). Serum levels or intake of vitamin D did not differ between the 2 groups. Subjects with elevated PTH in both 1995 and 1998 had significantly lower bone mineral content and bone mineral density in the lumbar spine than did those with persistently normal PTH levels (P<0.05). In the females, but not in the males, the systolic and diastolic blood pressures were significantly higher in those with elevated serum PTH (158.0+/-27.5 versus 141.5+/-19.2 mm Hg and 90. 5+/-13.6 versus 82.6+/-8.6 mm Hg, respectively; P<0.01). This difference was even more pronounced when those with persistently elevated PTH were considered separately. In conclusion, reduced intake of calcium is frequently associated with high levels of serum PTH. This is associated with moderately reduced bone mineral content and bone mineral density in the lumbar spine. In women, high levels of serum PTH are also associated with markedly increased blood pressure.

Population-based study of age at menopause and ultrasound assessed carotid atherosclerosis: The Tromsø Study.

Early menopause has been associated with higher prevalence and incidence of cardiovascular disease and death than late menopause, indicating that early loss of ovarian function and subsequent deficiency of estrogen may promote such diseases. No population-based studies have, however, examined the relation between age at menopause and atherosclerosis. We assessed the prevalence and the extent of carotid atherosclerosis by high-resolution B-mode ultrasound in 2588 postmenopausal women who participated in a population health survey. Information about age at menopause and menarche, parity, use of hormone replacement therapy, and prevalent diseases was collected, and cardiovascular risk factor levels were measured. Women with late menopause and women who ever had used postmenopausal estrogens had significantly less atherosclerosis than women with early menopause and those with never use of estrogen. This study provides further support for the hypothesis that estrogen protects women against cardiovascular disease.

Relationship between apolipoprotein E polymorphism, postprandial hyperlipemia and hemostatic variables in patients with combined hyperlipemia.

BACKGROUND AND AIM: Combined hyperlipemia is a common lipid abnormality associated with coronary heart disease (CHD). Aim of this study was to investigate the relationship between this abnormality and hemostatic risk factors related to thrombosis. METHODS AND RESULTS: Forty-one patients were examined in the fasting state and during postprandial hyperlipemia. They had high levels of factor VIIc in the fasting state. During postprandial hyperlipemia a highly significant (p < 0.001) increase of activated factor (VIIa) occurred. This activation was not correlated to the increase in free fatty acids, but to the degree of postprandial hypertriglyceridemia. The absolute postprandial triglyceridemia was highest in subjects with the apolipoprotein (apo) E2 allele. Tissue factor pathway inhibitor activity (TFPIa) was correlated to LDL cholesterol and apo B concentrations and was highest in subjects with genotypes containing the E4 allele. CONCLUSIONS: Subjects with combined hyperlipemia may have an increased thrombotic risk related to activation of factor VII during postprandial hyperlipemia. Subjects with genotypes including the apoE4 allele may have a high lipid risk profile associated with high levels of LDL cholesterol.