Repeated measurements of carotid atherosclerosis and future risk of venous thromboembolism: the Tromsø Study.

Essentials The relationship between atherosclerosis and venous thromboembolism (VTE) is controversial. In total, 10 426 participants recruited from the general population were included. Carotid intima media thickness and total plaque area was not associated with VTE. There was no association between plaque initiation or plaque progression and subsequent VTE. SUMMARY: Background Whether a relationship between atherosclerosis and subsequent venous thromboembolism (VTE) exists is controversial. Objective To investigate the association between carotid atherosclerosis and VTE by using repeated measurements of intima media thickness (IMT) and total plaque area (TPA) in participants recruited from the general population. Methods Participants were recruited from the fourth (1994-1995), fifth (2001-2002) and sixth (2007-2008) surveys of the Tromsø Study. In total, 10 426 participants attended, for whom measurements of carotid IMT and TPA and potential confounders were updated at each available survey. Time-varying Cox regression models were used to calculate hazard ratios (HRs) of VTE across various levels of IMT and TPA adjusted for age, sex, and body mass index. Results There were 368 incident VTE events during a median follow-up of 10.8 years. Participants with increasing IMT were, on average, older and had a less favorable cardiovascular risk profile. There was no association between tertiles of increasing TPA and the risk of VTE in the time-varying model, and increasing IMT was not associated with an increased risk of VTE (HR 0.96, 95% confidence interval [CI] 0.86-1.07). Neither plaque formation nor plaque progression was associated with the risk of VTE (respectively: HR 1.00, 95% CI 0.98-1.02; and HR 0.96, 95% CI 0.84-1.11). Conclusion Carotid IMT and TPA were not associated with an increased risk of VTE in time-varying analyses. Furthermore, there was no association between plaque initiation or plaque progression and subsequent VTE.

Carotid atherosclerosis and relation to growth of infrarenal aortic diameter and follow-up diameter: the Tromsø Study.

OBJECTIVES: This research aims to study how carotid atherosclerosis is related to growth of infrarenal aortic diameter and aneurysmal formation. DESIGN: Population-based follow-up study. MATERIALS AND METHODS: At baseline, ultrasound examination of the carotid artery and the abdominal aorta was performed in 4241 persons from a general population with no evidence of abdominal aortic aneurysm (AAA). The burden of atherosclerosis was assessed as carotid total plaque area (TPA). After a mean follow-up of 6.3 years, a new ultrasound examination was performed and measurements of the aortic diameter and carotid TPA were repeated. The effects on aortic diameter progression, follow-up diameter and risk for AAA were assessed in multiple linear and logistic regression models according to carotid TPA, adjusted for known risk factors. RESULTS: When analysing AAA as a dichotomous variable, a borderline association between atherosclerosis and AAA could be demonstrated. When modelling aortic diameter as a continuous variable, a 1-SD increase in 5 years' carotid plaque area (ΔTPA) was associated with a 0.12-mm growth in infrarenal aortic diameter (standard error (SE) 0.04) and a 0.20-mm wider aorta at follow-up (SE 0.06). No independent relation was seen for baseline atherosclerosis. CONCLUSIONS: Carotid plaque progression was positively related to growth in infrarenal aortic diameter and aortic diameter at follow-up. Whether this co-variation between plaque growth and aortic diameter growth is causally related or independent events is still an open question.

Carotid artery plaque progression and cognitive decline: the Tromsø Study 1994-2008.

BACKGROUND: Carotid atherosclerosis is a risk factor for stroke and cognitive decline, but knowledge on how progression of carotid atherosclerosis affects cognitive function in stroke-free individuals is scarce. METHODS: In the population-based Tromsø study, we calculated the change in ultrasound-assessed carotid plaque number and total plaque area from baseline (survey 4) to follow-up 7 years later (survey 5) in 4274 middle-aged stroke-free subjects. Cognitive function was assessed at follow-up by the verbal memory test, the digit-symbol coding test, and the tapping test and repeated after an additional 6 years in a subgroup of 2042 subjects (survey 6). Associations between the average of survey 4 and survey 5 plaque scores and the progression of plaque scores and cognitive test scores were assessed in regression analyses adjusted for baseline age, sex, education, depression, and cardiovascular risk factors. RESULTS: Progression of total plaque area was associated with lower scores in the digit-symbol coding test (multivariable adjusted standardized ß, -0.03; 95% CI, -0.05 to -0.00; P = 0.04) and the tapping test (ß, -0.03; 95% CI, -0.06 to -0.00; P = 0.03). Similar results were seen for progression of plaque number. The average plaque scores were associated with lower scores in all cognitive tests (P-values ≤ 0.01). No association was found between plaque scores and cognitive decline. CONCLUSIONS: The average plaque scores were associated with lower scores in all cognitive tests. Progression of plaque scores was associated with lower scores in the digit-symbol coding test and the tapping test, but not with the verbal memory test or with cognitive decline.

Serum osteoprotegerin, sRANKL and carotid plaque formation and growth in a general population--the Tromsø study.

SUMMARY BACKGROUND: Intervention studies in animal models suggest that osteoprotegerin (OPG) functions as an inhibitor or marker of atherosclerosis, whereas one prospective epidemiological study in humans indicated that OPG was an independent risk factor for progression of atherosclerosis. OBJECTIVE: To study the association between serum levels of OPG, soluble RANK ligand (sRANKL) and carotid artery plaque formation and plaque growth. PATIENTS/METHODS: The prevalence of carotid plaque and plaque area were assessed by ultrasonographic imaging at baseline and after 7 years follow-up in 2191 men and 2329 women who participated in a population-based study. RESULTS: OPG was significantly associated with atherosclerotic plaque burden and cardiovascular risk factors such as age, body mass index, blood pressure, total cholesterol, HDL cholesterol, HbA1c and fibrinogen at baseline, but not with sRANKL. In subjects without plaque at baseline, OPG predicted plaque formation in crude analysis in both women and men, but not after adjustment for age and other atherosclerotic risk factors. OPG predicted plaque growth in women (+1.8 mm(2), 0.6-3.0) (mean, 95% CI) per 1 SD increase in OPG (P = 0.003), whereas no associations were demonstrated in men (0.1 mm(2) (-1.3-1.4), P = 0.93). Soluble RANKL did not predict plaque formation or plaque growth. CONCLUSIONS: OPG was an independent predictor of plaque growth in women, but not in men, suggesting gender-specific actions of OPG in plaque growth. OPG was not associated with novel plaque formation.

Ultrasonographic measurements of subclinical carotid atherosclerosis in prediction of ischemic stroke.

Carotid intima-media thickness (IMT) and plaque measurements are widely used to quantify atherosclerosis and assess the risk of future stroke, and are used as surrogate endpoints for clinical disease. In recent years, it has become clear that carotid IMT and plaque reflect biologically and genetically different aspects of the atherosclerotic process, and are differentially related to risk factors and cardiovascular disease. Plaques are focal manifestations of atherosclerosis while increased IMT represents mainly hypertensive medial hypertrophy. Several prospective studies have showed that IMT and plaque measurements, such as total plaque area and plaque number, are predictive of future stroke. Plaque echogenicity predicts future stroke independent of plaque size. The contribution of IMT and plaque measurements in individual stroke risk prediction in the general population seems to be limited, but may be useful as a tool for individual stratification of high-risk patients.

Endogenous testosterone and the prospective association with carotid atherosclerosis in men: the Tromsø study.

The role of testosterone in the development of cardiovascular disease is controversial. Recent observational studies, however, suggest a protective role of normal endogenous testosterone levels in the development of atherosclerosis. In a cohort from the Tromsø study, 1,101 men had both hormone-levels measured and the right carotid artery examined by ultrasound in 1994 and 2001. We studied the prospective association between sex hormone-levels and progression of carotid intima-media thickness (IMT) and plaque area from 1994 to 2001. We also performed a cross-sectional study of 2,290 men from the population in 2001. The data were analysed by univariate correlations, analyses of covariance and multiple linear regression analyses. In the cross-sectional study, we found an inverse association between testosterone levels and total carotid plaque area (P < 0.05), after adjusting for age, systolic blood pressure, smoking and use of lipid-lowering drugs. We found no prospective associations between sex hormone-levels and change in plaque area or IMT from 1994 to 2001. The lack of prospective associations in our study may be due to increased use of anti-hypertensive and lipid-lowering drugs from 1994 baseline to follow-up.

Proinsulin:insulin and insulin:glucose ratios as predictors of carotid plaque growth: a population-based 7 year follow-up of the Tromsø Study.

AIMS/HYPOTHESIS: Proinsulin is increased in persons at cardiovascular risk. Increased secretion of proinsulin relative to insulin has been suggested as a sign of defective conversion of proinsulin to insulin and C-peptide and is associated with beta cell dysfunction. It has also been suggested that proinsulin has more of a pro-atherogenic effect than insulin, the levels of which are also increased in the insulin resistance state. In this prospective population-based study, we examined whether the proinsulin:insulin ratio (PIR) or insulin:glucose ratio (IGR, an insulin resistance surrogate) predicted carotid plaque size in nondiabetic participants. MATERIALS AND METHODS: The study included 1,859 men and 1,998 women aged 25-82 years from the Tromsø Study, who were examined with B-mode high resolution ultrasound at baseline in 1994-1995 and at follow-up in 2001-2002. All images were computer processed to yield mm(2) measures of plaque. Proinsulin and insulin were measured at baseline. All analyses were stratified for sex. RESULTS: After adjusting for age, baseline plaque area, BMI, cholesterol, HDL-cholesterol, HbA(1c), IGR, albumin:creatinine ratio, fibrinogen, BP and lifestyle factors (tobacco smoking, alcohol consumption, physical activity), PIR was significantly associated with plaque size at follow-up in women but not men. For each SD in the PIR in women, the mean plaque area increased by 0.97 mm(2) (95% CI 0.44-1.50). IGR was not associated with carotid plaque size. CONCLUSIONS/INTERPRETATION: The PIR is associated with progressive carotid artery plaque size in women.

[Serologic screening for neurosyphilis]. / Syfilisscreening av nevrologiske pasienter.

BACKGROUND: Syphilis serology is analysed in all patients admitted as in-patients to the Department of Neurology in Tromsø. In this study we examined the utility of performing routine laboratory testing for syphilis in neurological patients. MATERIAL AND METHODS: We registered all in-patients in the Department of Neurology with a confirmed diagnosis of syphilis during a ten-year period (1990-1999). Additionally, we calculated the cost of performing laboratory tests of all hospitalised patients in this period. RESULTS: From a total of 8,637 patients, we identified five patients with syphilis, one of them with neurosyphilis. This patient had impaired cognitive functions at the time of admittance and a broad spectrum of neurological deficits suggesting a serious neurological disease. A positive syphilis serology confirmed the diagnosis and treatment was initiated. The mean cost for Treponema pallidum serological screening in neurological patients during 10 years was calculated to be about NOK 17,000 per year. INTERPRETATION: Tertiary syphilis is a serious disease with symptoms often mimicking other diseases. Although the laboratory tests for syphilis have been performed in every in-patient admitted to the neurological ward, a speedier diagnosis of neurosyphilis could not be detected in any patient in a ten-year hospital material. Routine serological examination for syphilis in neurological patients is therefore not recommended in this geographical area.

[Small fiber neuropathy]. / Tynnfiberneuropati.

A common sign of distal small fibre neuropathy is dysesthesias, especially burning sensation distally in the extremities. These symptoms are often difficult to treat with conventional analgesics. In the course of the disease, the patient may become less sensitive to pain and changes in temperature, but clinical signs may nevertheless be minor and often difficult to detect by clinical examination. Dysautonomic features are also common. Selective affection of small fibres may occur in the form of pure small fibre neuropathy, but this may also be an early manifestation of general sensorimotor polyneuropathy. Common causes are diabetes mellitus, alcoholism, and amyloidosis. Abnormalities in small diameter fibres may be detected by quantitative sensory testing of temperature and pain thresholds, and by autonomic tests. We describe four patients with polyneuropathy with a predominance of small fibre involvement.