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• Prevalence of intracranial and extracranial artery stenosis is similar. • Intracranial ICA and posterior circulation are primarily affected. • May be a target for primary prevention. • Imaging modality and assessment methods affect the ability for detecting ICAS. Data on prevalence of intracranial artery stenosis (ICAS) in Western populations is sparse. The aim of the study was to assess the prevalence and risk factors for ICAS in a mainly Caucasian general population. We assessed the prevalence of ICAS in 1847 men and women aged 40 to 84 years who participated in a cross-sectional population-based study, using 3-dimensional time-of-flight 3 Tesla magnetic resonance angiography. ICAS was defined as a focal luminal flow diameter reduction of ≥50 %. The association between cardiovascular risk factor levels and ICAS was assessed by multivariable regression analysis. The overall prevalence of ICAS was 6.0 % (95 % confidence interval (CI) 5.0–7.2), 4.3 % (95 % CI 3.1–5.7) in women and 8.0 % (95 % CI 6.3–10.0) in men. The prevalence increased by age from 0.8 % in 40-54 years age group to 15.2 % in the 75-84 years age group. The majority of stenoses was located to the internal carotid artery (52.2 %), followed by the posterior circulation (33.1 %), the middle cerebral artery (10.8 %) and the anterior cerebral artery (3.8 %). The risk of ICAS was independently associated with higher age, male sex, hypertension, hyperlipidemia, diabetes mellitus, current smoking and higher BMI. The prevalence of ICAS in a general population of Caucasians was relatively high and similar to the prevalence of extracranial internal carotid artery stenosis in previous population-based studies. [ABSTRACT FROM AUTHOR]

Objective: We analyzed data from the Norwegian Stroke Registry (NSR) to study access to and outcomes of decompressive hemicraniectomy for brain infarction in a nationwide routine clinical setting. We also discretionary assessed whether the outcomes were comparable with those achieved in randomized controlled trials (RCTs), and whether the use was in accordance with guidelines.Methods: The NSR is a nationwide (population 5.3 million) clinical quality registry. We included all stroke-cases operated in 2017 through 2019, and retrieved data on baseline characteristics, treatment and functional outcome after three months (dichotomized modified Rankin Scale score; favorable (0-3) or unfavorable (4-6)). Crude treatment rates and the expected proportion of patients transferred from a local hospital to a stroke-center for the operation were estimated, based on the total population's distribution of residency.Results: The 68 cases were 17 (25%) women and 51 (75%) men with a median National Institute of Health Stroke Scale (NIHSS) score on admission of 14.0 (inter-quartile range (IQR) 11.0) and a median time from onset to hemicraniectomy of 34.3 (IQR 40.9) hours. The crude treatment rate varied between regions from 0.29 to 1.40 operations per 100,000 population per year, and the proportion transferred from a local hospital (50%) was lower than expected (68%). A favorable outcome was achieved in 20/52 (38.5%) cases.Conclusions: The findings indicate gender- and geographic-inequalities in access. Among operated cases, outcomes were comparable with those reported from RCTs, and the use in accordance with recommendations in the current guidelines from the American Stroke Association. [ABSTRACT FROM AUTHOR]

Current knowledge of the effect of fish consumption on risk of venous thromboembolism (VTE) is scarce and diverging. Therefore, the purpose of the present study was to investigate the impact of fish consumption and fish oil supplements on the risk of VTE in a population-based cohort. Weekly intake of fish for dinner and intake of fish oil supplements during the previous year were registered in 23,621 persons aged 25-97 y who participated in the Tromsø Study from 1994 to 1995. Incident VTE events were registered throughout follow-up (31 December 2010). Cox-regression models were used to calculate HRs for VTE, adjusted for age, body mass index, sex, triglycerides, HDL cholesterol, physical activity, and education level. During a median of 15.8 y of follow-up there were 536 incident VTE events. High fish consumption was associated with a slightly reduced risk of VTE. Participants who ate fish ≥3 times/wk had 22% lower risk of VTE than those who consumed fish 1-1.9 times/wk (multivariable HR: 0.78; 95% CI: 0.60, 1.01; P = 0.06). The addition of fish oil supplements strengthened the inverse association with risk of VTE. Participants who consumed fish ≥3 times/wk who additionally used fish oil supplements had 48% lower risk than those who consumed fish 1-1.9 times/wk but did not use fish oil supplements (HR: 0.52; 95% CI: 0.34, 0.79; P = 0.002). In conclusion, a high weekly intake (≥3 times/wk) of fish was associated with a slightly reduced risk of VTE, and the addition of fish oil supplements strengthened the inverse effect. [ABSTRACT FROM AUTHOR]

Abstract: Background: Weight loss has been associated with increased mortality, but findings have been inconsistent. Objective: The aim of this study was to examine the association between weight loss and mortality, with a focus on gender differences. Methods: This was a population-based cohort study in northern Norway of adults, aged 20 to 54 years in 1979, who participated in 2 or 3 consecutive health surveys in 1979–80, 1986–87, and 1994–95. Weight and height were measured at each survey. The Cox proportional hazards regression model was used to estimate hazard ratios for mortality between levels of body mass index (BMI) change during 11 years of follow-up. Participants with prior cardiovascular disease or cancer, or incident cancer within the first 2 years of follow-up, were excluded, as were participants who were pregnant, had missing data, or did not give written consent. Results: A total of 4881 men and 5051 women participated in the present study. The mean age at start of follow-up was 50.8 years (range, 35–70 years) in men and 49.2 years (range, 35–65 years) in women. In men, weight loss was associated with increased all-cause, cardiovascular, and noncardiovascular mortality. The hazard ratio for men for all-cause mortality with a 10-year BMI decrease of 2 kg/m2 versus a BMI increase of 1 kg/m2 was 2.09 (95% CI, 1.56–2.81). The association was not significantly modified by initial BMI, age, smoking status, or self-reported attempts of weight loss, or by exclusion of subjects with self-reported poor health, diabetes mellitus, high blood pressure, or high alcohol intake. In women, no association between BMI change and mortality was observed. However, in the subgroup of women who reported no weight-loss attempts, BMI change was significantly associated with mortality risk (P = 0.022). Conclusions: In this study of a Norwegian population, weight loss was associated with excess mortality in men in all subgroups of weight-loss attempts, daily smoking, and overweight. In women, the only significant effect of BMI change on mortality was observed in those who reported no weight-loss attempts. The observed findings could not be explained by preexisting disease. [Copyright &y& Elsevier]

Abstract: Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily involved in the regulation of bone metabolism and vascular calcification. High serum values of OPG are associated with cardiovascular disease in humans. The purpose was to investigate serum OPG levels in subclinical carotid atherosclerosis and the relation between OPG levels and plaque morphology. OPG levels were compared in 29 persons with echogenic carotid plaques, 30 persons with echolucent plaques and 41 persons without carotid plaques, all recruited from a population health study. Computerized assessment of plaque echogenicity was done by use of the gray scale median (GSM). Participants with echogenic carotid plaques had lower serum OPG level (1.23ng/ml; 1.02–1.48) (geometric mean; 95% CI) than persons with echolucent plaques (1.76ng/ml; 1.46–2.14) and those without plaques (1.89ng/ml; 1.60–2.21). OPG and PTH were independently related to GSM. A significant trend for decrease in GSM across quartiles of OPG was found (p =0.003) which remained significant even after adjustment for PTH and smoking. The present study demonstrates lower serum OPG levels in persons with subclinical echogenic carotid plaques and identified an inverse relation between serum OPG and plaque echogenicity. The findings support the concept that OPG may play an important role in arterial calcification. [Copyright &y& Elsevier]

Abstract: Background: Inflammatory biomarkers are reported as risk factors for atrial fibrillation (AF), but their impact is uncertain. Objective: We investigated the associations between inflammatory biomarkers and future AF in a large general cohort. Methods: Available markers were white blood cells (WBCs) with subgroups, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and osteoprotegerin (OPG). A total of 6315 men and women from a population survey in Tromsø, Norway in 1994 to 1995 were followed for a mean of 10.9 years. Mean age at baseline was 60 years. Measurements of height, weight, blood pressure, heart rate, total cholesterol, high-density lipoprotein (HDL) cholesterol, WBC count, and information on diabetes, angina, myocardial infarction, and antihypertensive treatment, were obtained at baseline. Fibrinogen, hs-CRP, and OPG were obtained at a follow-up visit. The outcome measure was first-ever AF, documented on an electrocardiogram. The Cox proportional hazards regression model was used to estimate hazard ratios of AF. Results: In the multivariable analysis, adjusted for traditional cardiovascular risk factors and other inflammatory biomarkers, hs-CRP was associated with AF in men only (hazard ratio = 1.14 for a 1 SD increase; 95% CI, 1.02–1.28). There was a significant increase in AF across quartiles of WBCs in men (P = 0.007) and in the total study population (P = 0.004). OPG was associated with AF in patients free of coronary heart disease at baseline. Fibrinogen and subgroups of WBCs showed no significant association with AF. Conclusion: This population-based cohort study showed that hs-CRP was independently associated with AF in men, but apparently not in women, and that patients with WBCs in the upper quartile had increased risk of AF. [Copyright &y& Elsevier]

Objective: The purpose of this study was to investigate the recurrence risk of hypertensive disorders in subsequent pregnancies and to explore the associations among hypertensive disorders of pregnancy and maternal cardiovascular risk factor profile and the development of cardiovascular diseases later in life. Study Design: We used population-based, cross-sectional data from the fourth survey of the Tromsø Study. Results: Preeclampsia in the first pregnancy increased the risk of recurrence in later pregnancies (relative risk, 6.6; 95% confidence interval, 5.5–7.9) compared with a normotensive first pregnancy. Women with a history of preeclampsia or nonproteinuric hypertension had an unfavorable cardiovascular risk profile. Hypertension was prevalent in 25% and 28% of the women, respectively. The carotid artery intima-media thickness and total carotid plaque area were significantly larger in women with previous preeclampsia. Conclusion: A strong association between hypertensive disorders of pregnancy and an increased risk of atherosclerosis and cardiovascular diseases was demonstrated by the assessment of risk factors that can be potentially modified. [ABSTRACT FROM AUTHOR]

Carotid intima media thickness (IMT) progression is increasingly used as a surrogate for vascular risk. This use is supported by data from a few clinical trials investigating statins, but established criteria of surrogacy are only partially fulfilled. To provide a valid basis for the use of IMT progression as a study end point, we are performing a 3-step meta-analysis project based on individual participant data. Objectives of the 3 successive stages are to investigate (1) whether IMT progression prospectively predicts myocardial infarction, stroke, or death in population-based samples; (2) whether it does so in prevalent disease cohorts; and (3) whether interventions affecting IMT progression predict a therapeutic effect on clinical end points. Recruitment strategies, inclusion criteria, and estimates of the expected numbers of eligible studies are presented along with a detailed analysis plan. [Copyright &y& Elsevier]

A reduced glomerular filtration rate (GFR) in chronic kidney disease is a risk factor for cardiovascular disease. However, evidence indicates that a high GFR may also be a cardiovascular risk factor. This issue remains unresolved due to a lack of longitudinal studies of manifest cardiovascular disease with precise GFR measurements. Here, we performed a cross-sectional study of the relationship between high GFR measured as iohexol clearance and subclinical cardiovascular disease in the Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6), a representative sample of the middle-aged general population. A total of 1521 persons without cardiovascular disease, chronic kidney disease, diabetes, or micro- or macroalbuminuria were examined with carotid ultrasonography and electrocardiography. The GFR in the highest quartile was associated with an increased odds ratio of having total carotid plaque area greater than the median of non-zero values (odds ratio 1.56, 95% confidence interval 1.02-2.39) or electrocardiographic signs of left ventricular hypertrophy (odds ratio 1.62, 95% confidence interval 1.10-2.38) compared to the lowest quartile. The analyses were adjusted for cardiovascular risk factors, urinary albumin excretion, and fasting serum glucose. Thus, high GFR is associated with carotid atherosclerosis and left ventricular hypertrophy and should be investigated as a possible risk factor for manifest cardiovascular disease in longitudinal studies. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Increased urinary albumin-excretion is a cardiovascular risk-factor. The cardiovascular risk of the metabolic syndrome (MetS) is debated. The aim of the present prospective, population-based study of non-diabetic individuals was to examine the association between low-grade urinary albumin-excretion, MetS, and cardiovascular morbidity and all-cause mortality. Methods: 5215 non-diabetic, non-proteinuric men and women participating in the Tromsø Study 1994–1995 were included. Urinary albumin–creatinine ratio (ACR) was measured in three urine samples. The participants were categorized into four groups by the presence/absence of MetS (the International Diabetes Federation definition) and ACR in the upper tertile (≥0.75mg/mmol). Results: Median follow-up time was 9.6 years for first ever myocardial infarction, 9.7 years for ischemic stroke and 12.4 years for mortality. High ACR (upper tertile)/MetS was associated with increased risk of myocardial infarction (hazard ratio (HR) 1.75; 95% confidence interval (CI): 1.30–2.37, p <0.001), stroke (HR 2.48; 95% CI: 1.66–3.71, p <0.001), and all-cause mortality (HR 1.63; 95% CI: 1.32–2.01, p <0.001) compared to reference (low ACR/no MetS). Similar associations were found for the high ACR/no MetS group. Low ACR/MetS was associated with myocardial infarction only (HR 1.82; 95% CI: 1.39–2.37, p <0.001). MetS predicted neither stroke nor mortality. Adjusted for its individual components, MetS was not associated with any end-point. Conclusions: ACR≥0.75mg/mmol was associated with cardiovascular morbidity and all-cause mortality independently of MetS. MetS was not associated with any end-point beyond what was predicted from its components. Thus, low-grade albuminuria, but not MetS, may be used for risk stratification in non-diabetic subjects. [Copyright &y& Elsevier]

Abstract: Background: Platelet microparticles (PMPs) possess proatherogenic and procoagulant properties which may play a role in atherogenesis and subsequent thromboembolic complications. The present study was conducted to investigate the possible relationship between carotid atherosclerosis and plasma concentrations of PMPs, and elucidate if plasma levels of PMPs were affected by postprandial hypertriglyceridemia. Methods and results: Subjects with ultrasound-assessed carotid atherosclerotic plaques (echogenic; n=20 and echolucent; n=20), assessed by ultrasonography, and subjects without carotid plaques (n=20) were recruited from a population-based study and underwent a standard fat tolerance test. Subjects with carotid plaques had significantly higher levels of large PMPs than subjects without carotid atherosclerotic plaques (96.7±50.4 µg/l versus 56.1±34.9 µg/l), after adjustments for traditional cardiovascular risk factors and use cardiovascular drugs (p=0.021). Plasma PMPs were not associated with plaque echogenicity. Postprandial hypertriglyceridemia induced a similar increase in plasma PMPs within all groups. Significant correlations were found between an increase in plasma triglycerides and percent elevation in total PMPs (r=0.29, p<0.05) and large PMPs (r=0.34, p<0.01) in the postprandial phase. Conclusions: Individuals with echogenic and echolucent carotid atherosclerotic plaques have statistically significant elevation of large plasma PMPs compared to age/sex-matched normal controls. Postprandial hypertriglyceridemia induces a significant, similar increase in plasma PMPs in individuals with and without carotid atherosclerotic plaques which could be of pathophysiological importance in atherogenesis. [Copyright &y& Elsevier]

Abstract: Background: Controversy exists whether persistent Chlamydia pneumoniae or cytomegalovirus infections cause initiation or progression of atherosclerosis. C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) has been proposed to be a more reliable marker of cardiovascular risk than are C. pneumoniae antibodies. Reported prevalences of C. pneumoniae DNA among cardiovascular patients vary greatly, indicating methodological limitations. There is an increasing concern that published results may have been biased by extensive use of less specific polymerase chain reaction (PCR) technology. Methods: C. pneumoniae DNA and cytomegalovirus DNA were determined by probe-based real-time PCR technology in PBMCs among subjects with echolucent (n =29) or echogenic (n =28) carotid artery plaques, and in controls without carotid plaques (n =38), all recruited from a population-based study. Samples were examined in multiple repeats with PCR assays targeting two different sequences of the genome for both microorganisms. Results and conclusion: IgG seropositivity was frequent in all three groups, confirming previous exposure, but C. pneumoniae DNA or cytomegalovirus DNA was not detected in a single PBMC sample by means of probe-based, highly sensitive, and specific real-time PCR assays. Our results indicate that persistent C. pneumoniae or CMV infection is not a common phenomenon in subjects with carotid atherosclerosis. [Copyright &y& Elsevier]

Abstract: 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 (κ 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 κ 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. (E-mail: einar.fosse@ism.uit.no) [Copyright &y& Elsevier]

Abstract: Background: Thrombogenicity of atherosclerotic plaque largely depends on plaque morphology and their content of tissue factor (TF) and tissue factor pathway inhibitor (TFPI). The relationship between morphological composition of plaque (lipid-rich or calcified) and expression of TF and TFPI in circulating blood monocytes and within the plaques is not characterized. Objective: To investigate whether lipid-rich (echolucent) or calcified (echogenic) morphology of carotid atherosclerotic plaques is associated with differences in TF and TFPI expression in circulating blood monocytes and within carotid atherosclerotic plaques. Methods: We studied levels of monocyte TF and TFPI mRNA and protein expression and association with traditional risk factors for atherosclerosis in asymptomatic subjects with echolucent (n=20) or echogenic (n=20) carotid plaques, or controls without carotid atherosclerosis (n=20) determined by ultrasonography. Sections of calcified or lipid-rich carotid plaques obtained from symptomatic patients were assessed for TF and TFPI antigen expression. Results: TF and TFPI surface presentation, surface TF/TFPI ratio, and TF activity were higher in monocytes obtained from subjects with echolucent than with echogenic plaques or controls without carotid atherosclerosis. Multiple regression analyses revealed inverse association between serum apoA1 and monocyte surface TF antigen expression (p=0.007), and positive association between serum apoB and monocyte surface TFPI expression (p=0.028). Sections from lipid-rich carotid plaques contained 2.5-fold more TF and 1.5-fold more TFPI antigens relative to calcified lesions, also yielding a higher TF/TFPI ratio. Conclusions: Our findings indicate that circulating monocytes of asymptomatic individuals with echolucent lipid-rich carotid atherosclerosis express an imbalance between TF and TFPI expression cohering with changes found within advanced carotid atherosclerotic plaques obtained from symptomatic patients. [Copyright &y& Elsevier]