Oddmund Joakimsen

Echolucent Plaques Are Associated With High Risk of Ischemic Cerebrovascular Events in Carotid Stenosis The Tromsø Study

BackgroundThe 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 ResultsA 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). ConclusionsSubjects 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.

Carotid Atherosclerosis Is a Stronger Predictor of Myocardial Infarction in Women Than in Men: A 6-Year Follow-Up Study of 6226 Persons: The Tromsø Study

Background and Purpose— Ultrasound of carotid arteries provides measures of intima media thickness (IMT) and plaque, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting. In this prospective, population-based study, we measured carotid IMT, total plaque area, and plaque echogenicity as predictors for first-ever myocardial infarction (MI). Methods— IMT, total plaque area, and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI. The subjects were followed for 6 years and incident MI was registered. Results— During follow-up, MI occurred in 6.6% of men and 3.0% of women. The adjusted relative risk (RR; 95% CI) between the highest plaque area tertile versus no plaque was 1.56 (1.04 to 2.36) in men and 3.95 (2.16 to 7.19) in women. In women, there was a significant trend toward a higher MI risk with more echolucent plaque. The adjusted RR (95% CI) in the highest versus lowest IMT quartile was 1.73 (0.98 to 3.06) in men and 2.86 (1.07 to 7.65) in women. When we excluded bulb IMT from analyses, IMT did not predict MI in either sex. Conclusions— In a general population, carotid plaque area was a stronger predictor of first-ever MI than was IMT. Carotid atherosclerosis was a stronger risk factor for MI in women than in men. In women, the risk of MI increased with plaque echolucency.

Risk Factors Related to Carotid Intima-Media Thickness and Plaque in Children With Familial Hypercholesterolemia and Control Subjects

To assess the relationship between risk factors for cardiovascular disease and early atherosclerotic changes in the carotid artery, we measured carotid intima-media thickness by B-mode ultrasonography in 61 boys and 29 girls 10 to 19 years old with familial hypercholesterolemia (FH) and 30 control subjects matched for age and sex. All were nonsmokers, and all the FH adolescents had a known mutation in the LDL receptor gene. Mean intima-media thickness in the far wall of the carotid bulb was greater (P = .03) in the FH group than in the control subjects: 0.54 mm (95% confidence interval [CI], 0.52 to 0.56) versus 0.50 mm (95% CI, 0.47 to 0.52). In the entire group, mean and maximum intima-media thicknesses in the carotid bulb were positively associated with levels of apolipoprotein B and fibrinogen after control for pubertal stage (r = .19 to .24; P < .05), as was male sex. Plasma total homocysteine was similar in the FH and control groups and was associated with mean and maximum intima-media thicknesses in the far wall of the common carotid artery and carotid bulb after control for pubertal stage (r = .22 to .28; P < .05). With the exception of the relation between plasma fibrinogen level and mean carotid bulb intima-media thickness, these associations were essentially unchanged in stepwise multiple linear regression analyses, allowing for the entry of BMI and level of HDL cholesterol into the analysis. Carotid artery plaque was present in 10% of the children with FH versus none of the control subjects. Children with plaque had a higher mean cholesterol-years score than children without plaque. These findings suggest that the classic lipid and hemostatic risk factors as well as plasma total homocysteine are associated with markers of early carotid atherosclerosis from the second decade of life. B-mode ultrasonography may prove to be a useful tool in risk stratification of children with FH.

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.

Reproducibility of Ultrasound Assessment of Carotid Plaque Occurrence, Thickness, and Morphology The Tromsø Study

BACKGROUND AND PURPOSE Ultrasonography is increasingly used in vascular research, but there is limited information about the reproducibility of the ultrasound method for screening purposes. In this study the reproducibility of ultrasound assessment of carotid plaque occurrence, thickness, and morphology was examined within the setting of a population health survey. METHODS In 1994/1995, 6720 participants in the Tromsø Study, Norway, underwent B-mode ultrasound scanning of the right carotid artery. The between- and within-sonographer reproducibility of ultrasound assessment of plaque occurrence and thickness was estimated by repeated scanning of a random sample of 107 participants. The between- and within-sonographer reproducibility of plaque morphology classification (echogenicity, four categories and heterogeneity, two categories) was determined by repeated reading of videotaped images of 119 randomly selected arteries with plaques. RESULTS Between- and within-sonographer agreement on plaque occurrence was substantial with kappa values (95% CI) of 0.72 (0.60 to 0.84) and 0.76 (0.63 to 0.89), respectively. Reproducibility of plaque thickness measurements was moderate, with mean absolute differences ranging between 0.25 and 0.55 mm (coefficients of variation between 13.8% and 22.4%). Agreement on plaque morphology classification was high, with kappa values ranging between 0.54 and 0.73. CONCLUSIONS Population screening using B-mode ultrasound provides a valuable means for the detection and morphological evaluation of carotid plaques, whereas measurements of plaque thickness are subject to considerable measurement error.

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.

Reproducibility of Ultrasonographically Determined Intima-Media Thickness Is Dependent on Arterial Wall Thickness The Tromsø Study

BACKGROUND AND PURPOSE We compared the reproducibility of B-mode ultrasonographic measurements of intima-media thickness (IMT) in various segments of the right carotid artery and examined whether measurement error was associated with IMT or cardiovascular risk factor levels. METHODS In 1994/1995 a total of 6676 participants in the Tromsø Study underwent ultrasound examination of common carotid artery IMT. Reproducibility of measurements was assessed by inviting 111 participants to a second ultrasound scan within 3 weeks of the first scan. On each occasion the subjects were examined by three sonographers. RESULTS The mean between-observer absolute differences in IMT in the far wall of the bifurcation and the near and far walls of the common carotid-artery were 0.15, 0.10, and 0.08 mm, respectively. The corresponding within-observer differences were 0.15, 0.10, and 0.06 mm, respectively. Approximately 70% to 80% of total measurement variability was due to differences among sonographers; the rest was attributable to within-reader variability. Measurement error increased significantly with increasing IMT: the increase was more than twofold over the range of measurements. Cardiovascular risk factor levels were not associated with measurement variability when we controlled for IMT. CONCLUSIONS We conclude that B-mode ultrasound provides reproducible estimates of the IMT in both the near and far walls of the carotid artery. Although measurement error is generally small, it increases proportionally with the level of IMT.

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.

Sex Differences in the Relationship of Risk Factors to Subclinical Carotid Atherosclerosis Measured 15 Years Later: The Tromsø Study

BACKGROUND AND PURPOSE Ultrasound measurement of carotid artery intima-media thickness (IMT) is regarded as a valid index of atherosclerosis. Determinants of IMT in cross-sectional studies have been established, but the long-term relationship between cardiovascular risk factors and subclinical atherosclerosis has not been investigated thoroughly. METHODS We included in the study 3128 middle-aged men and women in Tromsø, Norway, who in 1980 attended the baseline examination with measurements of cardiovascular risk factors and who underwent carotid ultrasonography after 15 years of follow-up. RESULTS Age, blood pressure, total cholesterol, HDL cholesterol, and body mass index were independent long-term predictors of IMT in both men and women. Triglyceride levels were associated with an increase in IMT in women only, while physical activity and smoking were predictors of IMT in men only. However, smoking was associated with increased risk of having atherosclerotic plaque in both men and women. There were no differences in the strength of risk factor effects on IMT in the common carotid artery and the carotid bifurcation. CONCLUSIONS The present study indicates that established cardiovascular risk factors are independent predictors of subclinical atherosclerosis measured after 15 years of follow-up. However, there may be significant sex differences in the relationship between triglycerides, smoking, and physical activity and the risk of atherosclerosis.

Monocyte Count Is a Predictor of Novel Plaque Formation. A 7-Year Follow-up Study of 2610 Persons Without Carotid Plaque at Baseline. The Tromsø Study

Background and Purpose— Activation of monocytes and differentiation into lipid-laden macrophages are fundamental events in generation of atherosclerotic lesions. There exist few data on monocyte activity and the risk for atherosclerosis. In this prospective population-based study, we examined whether monocyte count in blood is a predictor of future plaque formation in persons without pre-existing carotid atherosclerosis. Methods— At baseline, we measured monocyte count, white cell count (WCC), fibrinogen, intima-media thickness (IMT), and traditional cardiovascular risk factors in 2610 men and women aged 25 to 82 years who on ultrasound had no plaque in their right carotid artery. After 7 years of follow-up, a new ultrasound screening was performed and the number of novel plaques was grouped as none, 1 plaque, and 2 or more plaques. Results— In multivariate analysis, monocyte count, age, sex, total cholesterol, current smoking, systolic blood pressure, and IMT were independent predictors of novel plaque formation. No significant association was found between plaque formation and either WCC or fibrinogen. For 1 standard deviation (0.17×109) increase in monocyte count, the risk of being in a higher plaque category increased by 18% (OR, 1.18; 95% CI, 1.08 to 1.29). In the highest monocyte quartile, the risk for having plaque compared with the lowest quartile was 1.85 (OR) (95% confidence interval, 1.41 to 2.43). Repeating the analysis without IMT did not change the monocyte estimate. Excluding subjects with cardiovascular disease and diabetes mellitus from analysis neither changed the monocyte estimate. Conclusion— Monocyte count is an independent predictor of future plaque formation in subjects without pre-existing carotid atherosclerosis.