Relation of common carotid artery lumen diameter to general arterial dilating diathesis and abdominal aortic aneurysms: the Tromsø Study.

In a cross-sectional, population-based study in Tromsø, Norway, the authors investigated correlations between lumen diameter in the right common carotid artery (CCA) and the diameters of the femoral artery and abdominal aorta and whether CCA lumen diameter was a risk factor for abdominal aortic aneurysm (AAA). Ultrasonography was performed in 6,400 men and women aged 25-84 years during 1994-1995. An AAA was considered present if the aortic diameter at the level of renal arteries was greater than or equal to 35 mm, the infrarenal aortic diameter was greater than or equal to 5 mm larger than the diameter of the level of renal arteries, or a localized dilation of the aorta was present. CCA lumen diameter was positively correlated with abdominal aortic diameter (r = 0.3, P < 0.01) and femoral artery diameter (r = 0.2, P < 0.01). In a multivariable adjusted model, CCA lumen diameter was a significant predictor of AAA in both men and women (for the fifth quintile vs. the third, odds ratios were 1.9 (95% confidence interval: 1.2, 2.9) and 4.1 (95% confidence interval: 1.5, 10.8), respectively). Thus, CCA lumen diameter was positively correlated with femoral and abdominal aortic artery diameter and was an independent risk factor for AAA.

Lack of significant association between intima-media thickness in the carotid artery and serum TSH level. The Tromsø Study.

BACKGROUND: Increased arterial wall intima-media thickness (IMT) is an early feature of atherosclerosis and has been reported to be altered in patients with thyroid dysfunction. The present study was performed to examine the relation between carotid artery intima-media thickness and possible variations in thyroid function in normal subjects using serum TSH as a surrogate index of thyroid function. DESIGN: A total of 2034 subjects (974 males) were studied, 1856 or whom were non-users of thyroxine. The subjects not taking thyroxine were classified into three groups, those with a low serum TSH (0.48 mIU/L (2.5 percentile, those with serum TSH from 0.48 to 4.16 mIU/L, and those with high serum TSH of >4.16 mIU/L (97.5 percentile). Carotid ultrasound was performed in each all 2034 subjects to determine IMT. RESULTS: Among those not taking thyroxine, subjects in the low serum TSH group had a higher mean IMT as compared to those in the normal and high serum TSH groups but the differences were not significant when adjusted for gender, age, smoking status, body mass index, systolic blood pressure and serum cholesterol (0.88 +/- 0.15 mm, 0.84 +/- 0.16 mm, and 0.84 +/- 0.24 mm respectively). Subjects taking thyroxine had significantly higher IMT than those not taking thyroxine (0.89 + 0.20 mm versus 0.84 + 0.17 mm, p<0.01). CONCLUSIONS: No significant relationship between carotid IMT and serum TSH levels was observed in normal, non thyroxine taking, subjects. Carotid IMT was increased in subjects taking thyroxine. Whether the increase in carotid IMT is due to thyroxine ingestion or underlying thyroid disease cannot be answered from the study.

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 for cerebral stroke]. / Risikofaktorer for hjerneslag.

BACKGROUND: Stroke is a heterogenic group of disorders. Cerebral infarction is the largest group (80-85%) and is followed by primary intracerebral hemorrhage and subarachnoid hemorrhage. This article gives a review of risk factors for cerebral stroke, with an emphasis on cerebral infarction. MATERIAL AND METHODS: The article is based on literature identified through Medline, with emphasis on prospective, population-based studies. RESULTS AND INTERPRETATION: Genetic studies of the Icelandic population have shown associations between single genes and common types of stroke, but it remains to be seen whether the results can be replicated in other populations. High blood pressure and cigarette smoking are the most important modifiable risk factors for stroke. Serum cholesterol is positively associated with cerebral infarction, but not with intracerebral hemorrhage. Diabetes, atrial fibrillation and carotid stenosis are important predictors of cerebral infarcts, especially in the elderly. Cohort studies and randomized trials have shown that hormone replacement therapy in women increases the risk of stroke, while modern oral contraceptives do not represent a risk factor for stroke in young women. There is a clear social gradient in stroke occurrence, with a higher incidence in lower social classes.

Elevated high-density lipoprotein cholesterol levels are protective against plaque progression: a follow-up study of 1952 persons with carotid atherosclerosis the Tromsø study.

BACKGROUND: There is an inverse relationship between HDL cholesterol and coronary heart disease. Experimental studies have indicated that HDL cholesterol may exert an antiatherogenic effect by inducing regression of atherosclerotic plaques and by turning lipid-rich plaques into more fibrotic lesions. In this prospective, population-based ultrasound study, we investigated how HDL cholesterol relates to carotid plaque progression. METHODS AND RESULTS: The study included 1952 men and women aged 25 to 82 years who had at least 1 plaque present in the right carotid artery at baseline examination (1994). All plaque images were computer processed to yield a measure of plaque area in square millimeters and echogenicity, expressed as the gray-scale median. After 7 years of follow-up, a new ultrasound screening was performed, and the changes in plaque area and echogenicity were assessed. In a multivariable adjusted model, HDL cholesterol, age, systolic blood pressure, and current smoking were independent predictors of plaque growth. For a 1-SD (0.41 mmol/L) lower HDL cholesterol level, mean (SE) plaque area increased by 0.93 mm2 (0.44 mm2; P=0.03). When users of lipid-lowering drugs were excluded from analysis, the HDL estimate was strengthened (beta=1.46 mm2, P=0.002). Although plaque area increased in 70% of cases, and most plaques became more echogenic over the follow-up interval, the plaques that became more echolucent grew more in size than those that became more echogenic (P=0.002). CONCLUSIONS: This study shows that a high level of HDL cholesterol reduces plaque growth in subjects with preexisting carotid atherosclerosis. Transformation of the plaque mass into higher echogenicity is associated with reduced growth. Our findings may indicate that HDL cholesterol stabilizes plaques and counteracts their growth by reducing their lipid content and inflammation.

Repeated visual and computer-assisted carotid plaque characterization in a longitudinal population-based ultrasound study: the Tromsø study.

In a longitudinal population-based ultrasound survey, we evaluated the reproducibility of carotid plaque detection, off-line vs. online visual classification of plaque echogenicity and computer-assisted plaque echogenicity (grey-scale median, GSM) classification and plaque area measurements. The number of paired observations in the reproducibility analyses was 107 in the baseline study and 83 in the follow-up study. In addition, 198 and 222 images were selected from the baseline and the follow-up study for GSM- and plaque-area analyses. The total number of plaque images (11,160) was used to obtain comparative reference values. Despite good agreement in the reproducibility study (kappa values ranging from 0.52 to 0.57), there was a substantial drift in online visual classification of plaque echogenicity during the survey period. Inter- and intraobserver agreement on computer-assisted GSM classification was substantial, with kappa values (95% CI) of 0.77 (0.73 to 0.80) and 0.79 (0.75 to 0.84), respectively. A systematic bias in plaque area measurements was observed. Visual online classification may introduce systematic measurement errors that are not intercepted in a reproducibility study of restricted duration. Computer-assisted off-line classification had better reproducibility. However, the method is influenced by measurement errors, both in the outlining of the plaque and in the standardization procedure.

Glycated hemoglobin level is strongly related to the prevalence of carotid artery plaques with high echogenicity in nondiabetic individuals: the Tromsø study.

BACKGROUND: High levels of HbA1c have been associated with increased mortality and an increased risk of atherosclerosis assessed as carotid intima-media thickness or plaque prevalence. In the present population-based study, we examined the association between HbA1c and plaque prevalence with emphasis on plaque echogenicity in subjects not diagnosed with diabetes. METHODS AND RESULTS: HbA1c measurements and ultrasonography of the carotid artery were performed in 5960 subjects (3026 women, 2934 men) 25 to 84 years of age. Plaque morphology was categorized into 4 groups from low echogenicity (soft plaque) to strong echogenicity (hard plaque). HbA1c was categorized into 5 groups: <5.0%, 5.0% to 5.4%, 5.5% to 5.9%, 6.0% to 6.4% and >6.4%. Carotid plaque prevalence increased with increasing HbA1c level (P for linear trend=0.002). The OR for hard plaques versus no plaques was 5.8 in the highest HbA1c group (>6.4%) compared with subjects in the lowest group (<5.0%) after adjustment for several possible confounders. The risk of predominantly hard plaques was also significantly associated with HbA1c levels, although the ORs at each level were somewhat lower than for hard plaques. With respect to the risk of soft plaques versus no plaques, no statistically significant relationship with HbA1c levels was found. CONCLUSIONS: Metabolic changes reflected by HbA1c levels may contribute to the development of hard carotid artery plaques, even at modestly elevated levels.

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 (0.17x10(9)) 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. CONCLUSIONS: Monocyte count is an independent predictor of future plaque formation in subjects without pre-existing carotid atherosclerosis.

Albuminuria as risk factor for initiation and progression of carotid atherosclerosis in non-diabetic persons: the Tromsø Study.

AIMS: High levels of microalbuminuria have been associated with severe atherosclerosis. In this prospective, population-based study, we examined whether urinary albumin-to-creatinine-ratios (ACR) in the lower range were associated with the initiation and progression of atherosclerosis. METHODS AND RESULTS: Carotid ultrasonography and measurements of ACR, fibrinogen, monocytes, white cell count, and well-established cardiovascular risk factors were performed in 4037 non-diabetic subjects, 2203 without, and 1834 with pre-existing plaques at baseline. After 7 years new ultrasound measurements were performed. In subjects without pre-existing plaques, 884 had developed at least one plaque during follow-up. Baseline ACR was significantly related to the area of the novel plaques (P for linear trend = 0.009 over the baseline ACR quartiles, after multiple adjustments). The relationship with ACR was clearly modified by fibrinogen (P = 0.001, for the interaction ACR x fibrinogen). Subjects with high levels of both ACR and fibrinogen developed plaques with the largest area. In subjects with pre-existing plaques, ACR was related to plaque-progression (P for linear trend = 0.026, after multiple adjustments). In these individuals, the interaction between fibrinogen and ACR on plaque-growth appeared only in those with minimal atherosclerosis at baseline. CONCLUSION: ACR is positively related to plaque-initiation and plaque-growth. This relationship is substantially modified by fibrinogen in previously plaque-free subjects.

Sex differences in plaque morphology may explain the higher male prevalence of myocardial infarction compared to angina pectoris. The Tromsø Study.

OBJECTIVES: To study whether the degree of carotid atherosclerosis and the male predominance of echolucent plaques could explain the sex difference in myocardial infarction (MI) compared to angina pectoris (AP). DESIGN: Ultrasound examination of the carotid artery was performed in 6727 persons. The presence of plaque, plaque thickness and number of segments with plaque were recorded. Plaque morphology in terms of echogenicity was scored as echolucent (soft plaque) or echogenic (hard plaque). A questionnaire was used to obtain information about coronary heart disease. RESULTS: In men with the most advanced atherosclerosis, the risk (OR, 95% CI) of having MI compared to those with no carotid atherosclerosis was less than half as the corresponding risk in women (2.2, 1.4-3.3 vs 5.3, 2.6-10.6). For MI, the male-to-female ratio was highest in the group with no carotid plaque and declined by increasing burden of atherosclerosis. For AP, the sex ratio was independent of the degree of atherosclerosis. CONCLUSIONS: The findings support the hypothesis that the sex difference in MI compared to AP is due to the higher male prevalence of echolucent plaque.

Low bone mineral density is related to echogenic carotid artery plaques: a population-based study.

In a 1994-1995 cross-sectional, population-based study of 2,543 men and 2,726 postmenopausal women aged 55-74 years in Tromsø, Norway, the authors assessed a possible relation between bone mineral density (BMD) and the prevalence of carotid artery plaques, with an emphasis on plaque morphology. BMD measurements of the forearm and ultrasonography of the carotid artery were performed. Study participants were divided into quartiles with respect to sex-specific BMD values. Prevalent plaques were categorized into four groups ranging from low echogenicity to high echogenicity. For echogenic plaques, a significant inverse correlation with BMD was found (p for linear trend=0.007 after adjustment for age, sex, and cardiovascular risk factors). For predominantly echogenic plaques, a similar but weaker association was indicated (p = 0.08); for predominantly echolucent and echolucent plaques, no significant associations were observed (p > or = 0.3). Subjects whose BMD values were in the highest quartile had a statistically significant lower risk of echogenic plaques than subjects whose BMD values were in the lowest quartile (odds ratio=0.51, 95% confidence interval: 0.31, 0.83). This study indicates that low bone mass is associated with an increased risk of echogenic calcified atherosclerotic plaques but not with a risk of echolucent plaques.