Carotid Plaque Score for Stroke and Cardiovascular Risk Prediction in a Middle-Aged Cohort From the General Population.

Background We aimed to explore the predictive value of the carotid plaque score, compared with the Systematic Coronary Risk Evaluation 2 (SCORE2) risk prediction algorithm, on incident ischemic stroke and major adverse cardiovascular events and establish a prognostic cutoff of the carotid plaque score. Methods and Results In the prospective ACE 1950 (Akershus Cardiac Examination 1950 study), carotid plaque score was calculated with ultrasonography at inclusion in 2012 to 2015. The largest plaque diameter in each extracranial segment of the carotid artery on both sides was scored from 0 to 3 points. The sum of points in all segments provided the carotid plaque score. The cohort was followed up by linkage to national registries for incident ischemic stroke and major adverse cardiovascular events (nonfatal ischemic stroke, nonfatal myocardial infarction, and cardiovascular death) throughout 2020. Carotid plaque score was available in 3650 (98.5%) participants, with mean±SD age of 63.9±0.64 years at inclusion. Only 462 (12.7%) participants were free of plaque, and and 970 (26.6%) had a carotid plaque score of >3. Carotid plaque score predicted ischemic stroke (hazard ratio [HR], 1.25 [95% CI, 1.15-1.36]) and major adverse cardiovascular events (HR, 1.21 [95% CI, 1.14-1.27]) after adjustment for SCORE2 and provided strong incremental prognostic information to SCORE2. The best cutoff value of carotid plaque score for ischemic stroke was >3, with positive predictive value of 2.5% and negative predictive value of 99.3%. Conclusions The carotid plaque score is a strong predictor of ischemic stroke and major adverse cardiovascular events, and it provides incremental prognostic information to SCORE2 for risk prediction. A cutoff score of >3 seems to be suitable to discriminate high-risk subjects. Registration Information clinicaltrials.gov. Identifier: NCT01555411.

Systolic blood pressure at age 40 and cognitive function 25 years later: the Akershus Cardiac Examination (ACE) 1950 Study.

OBJECTIVES: Hypertension in midlife is a risk factor for cognitive impairment. Still, the ideal midlife blood pressure (BP) remains unknown. We examined associations between different systolic blood pressure (SBP) levels at the age of 40-43 years and change in SBP over a 25-year period with cognitive function at age 62-65 years. METHODS: We included 2424 individuals born in 1950 who had participated both in the Age 40 Program (1990-1993) and the Akershus Cardiac Examination (ACE) 1950 Study (2012-2015). The exposure was SBP at age 40-43 years and the outcome was cognitive function at age 62-65 years, assessed with Montreal Cognitive Assessment, Delayed recall trial from the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task, and Trail Making Test part B (TMT B). RESULTS: Participants were 40.1 ±â€Š0.3 years old with mean SPB 128 ±â€Š13 mmHg at the Age 40 Program, and 63.9 ±â€Š0.6 years old with mean SPB 138 ±â€Š18 at the ACE 1950 Study. Adjusted linear regressions showed no associations between SBP and subsequent cognitive function. In logistic regressions, individuals with SBP ≥140 mmHg, compared to individuals with SBP <120 mmHg (odds ratio 2.29, 95% confidence interval 1.28-4.10, P-value 0.005) had increased risk of an abnormal TMT B-score. Change in SBP during the 25-year follow-up was not associated with cognitive function. CONCLUSIONS: SBP ≥140 mmHg at age 40-43 was associated with reduced capacity on TMT B, a domain specific cognitive test sensitive to vascular impairment. No other associations were found between SBP, or change in SBP, and cognitive function.

Cardiac troponin I measured with a very high sensitivity assay predicts subclinical carotid atherosclerosis: The Akershus Cardiac Examination 1950 Study.

AIMS: Concentrations of cardiac troponin I (cTnI) are associated with incident ischemic stroke and predict the presence and severity of coronary atherosclerosis. Accordingly, we hypothesized that concentrations of cTnI measured with a very high sensitivity (hs-) assay would be associated with subclinical stages of carotid atherosclerosis in the general population. METHODS: We measured hs-cTnI on the Singulex Clarity System in 1745 women and 1666 men participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants were free from known coronary heart disease and underwent extensive cardiovascular phenotyping at baseline, including carotid ultrasound. We quantified carotid atherosclerosis by the carotid plaque score, carotid intima-media thickness (cIMT) and the presence of hypoechoic plaques. RESULTS: Concentrations of hs-cTnI were measurable in 99.8% of study participants and were significantly associated with increased carotid plaque score (odds ratio for quartile 4 of hs-cTnI 1.59, 95% CI 1.22 to 2.07, p for trend < 0.001) and cIMT (odds ratio for quartile 4 of hs-cTnI 1.57, 95% CI 1.02 to 2.42, p for trend = 0.036), but not with the presence of hypoechoic plaques. hs-cTnI concentrations significantly improved reclassification and discrimination models in predicting carotid plaques when added to cardiovascular risk factors, no improvements were evident in predicting cIMT or hypoechoic plaques. CONCLUSION: Concentrations of cTnI measured with a very high sensitivity assay are predictive of carotid atherosclerotic burden, a phenomenon likely attributable to common risk factors of subclinical myocardial injury, coronary and carotid atherosclerosis.

Plasma Trans Fatty Acid Levels, Cardiovascular Risk Factors and Lifestyle: Results from the Akershus Cardiac Examination 1950 Study.

Intake of industrially produced trans fatty acids (iTFAs) has previously been associated with dyslipidemia, insulin resistance, hypertension and inflammation, as well as increased cardiovascular (CV) morbidity and mortality. iTFA intake declined in Norway after the introduction of legislative bans against iTFA consumption. However, the relationship between the current iTFA intake and CV health is unclear. The aim of the present study was to investigate the association between current iTFA intake, reflected by plasma iTFA levels, and established CV risk factors. We also examined the associations between plasma ruminant TFA levels and CV risk factors. In this cross-sectional study, we included 3706 participants from a Norwegian general population, born in 1950 and residing in Akershus County, Norway. The statistical method was multivariable linear regression. Plasma iTFA levels were inversely associated with serum triglycerides (p < 0.001), fasting plasma glucose (p < 0.001), body mass index (p < 0.001), systolic and diastolic blood pressure (p = 0.001 and p = 0.03) and C-reactive protein (p = 0.001). Furthermore, high plasma iTFA levels were associated with higher education and less smoking and alcohol consumption. We found that plasma ruminant trans fatty acids (rTFA) levels were favorably associated with CV risk factors. Furthermore, plasma iTFA levels were inversely associated with CV risk factors. However, our results might have been driven by lifestyle factors. Overall, our findings suggest that the current low intake of iTFAs in Norway does not constitute a threat to CV health.

Plasma linoleic acid levels and cardiovascular risk factors: results from the Norwegian ACE 1950 Study.

BACKGROUND: A high intake of linoleic acid (LA), the major dietary polyunsaturated fatty acid (PUFA), has previously been associated with reduced cardiovascular (CV) morbidity and mortality in observational studies. However, recent secondary analyses from clinical trials of LA-rich diet suggest harmful effects of LA on CV health. METHODS: A total of 3706 participants, all born in 1950, were included in this cross-sectional study. We investigated associations between plasma phospholipid levels of LA and CV risk factors in a Norwegian general population, characterized by a relative low LA and high marine n-3 PUFA intake. The main statistical approach was multivariable linear regression. RESULTS: Plasma phospholipid LA levels ranged from 11.4 to 32.0 wt%, with a median level of 20.8 wt% (interquartile range 16.8-24.8 wt%). High plasma LA levels were associated with lower serum low-density lipoprotein cholesterol levels (standardized regression coefficient [Std. ß-coeff.] -0.04, p = 0.02), serum triglycerides (Std. ß-coeff. -0.10, p < 0.001), fasting plasma glucose (Std. ß-coeff. -0.10, p < 0.001), body mass index (Std. ß-coeff. -0.13, p < 0.001), systolic and diastolic blood pressure (Std. ß-coeff. -0.04, p = 0.03 and Std. ß-coeff. -0.02, p = 0.02, respectively) and estimated glomerular filtration rate (Std. ß-coeff. -0.09, p < 0.001). We found no association between plasma LA levels and high-density lipoprotein cholesterol levels, glycated hemoglobin, carotid intima-media thickness, or C-reactive protein. CONCLUSION: High plasma LA levels were favorably associated with several CV risk factors in this study of a Norwegian general population.

Carotid Atherosclerosis is Associated with Middle Cerebral Artery Pulsatility Index.

BACKGROUND AND PURPOSE: Pulsatility index (PI) in the middle cerebral artery (MCA) is considered a measure of peripheral vascular resistance. Several established cardiovascular risk factors are common for both MCA PI and carotid atherosclerosis. Accordingly, in the present study we hypothesized an association between ultrasound-derived indices of carotid atherosclerosis and MCA PI. METHODS: All residents in Akershus County, born in 1950, were invited to a cardiovascular examination, The Akershus Cardiac Examination (ACE) 1950 Study (2012-2015). A thorough ultrasound examination was performed to assess indices of atherosclerosis in the carotid arteries, and PI in the MCAs. In all, 3154 (85.1%) had adequate transcranial and carotid data. Associations between indices of carotid atherosclerosis and MCA PI were assessed by regression analyses adjusted for established cardiovascular risk factors. RESULTS: Mean age was 64 (standard deviation [SD]: .6) years, and 1,357 (43%) were women. Mean MCA PI was .97 (SD: .17). Participants in the upper quartile of MCA PI had higher pulse pressure, more frequently hypertension, diabetes mellitus, and a history of coronary artery disease. Both carotid plaque score (B .007 [95% CI: .003-.010]) and carotid intimamedia thickness (B .173 [95% CI: .120-.226]) were significantly associated with MCA PI in adjusted analysis. The model R2 was .055. CONCLUSION: In a population-based sample of middle-aged adults, ultrasound-derived indices of carotid atherosclerosis were independently associated with MCA PI. However, the overall explained variance of MCA PI was low, suggesting other factors than atherosclerosis and cardiovascular risk factors to play an important role for MCA PI.

Plasma marine n-3 polyunsaturated fatty acids and cardiovascular risk factors: data from the ACE 1950 study.

PURPOSE: A high intake of marine n-3 polyunsaturated fatty acids (PUFAs) might improve cardiovascular (CV) health. We conducted a cross-sectional study to investigate associations between plasma phospholipid levels of marine n-3 PUFAs and CV risk factors, educational level, physical activity and smoking habits. METHODS: A total of 3706 individuals from a general population, all born in 1950 and residing in Akershus County, Norway, were included in this study. The main statistical approach was multivariable adjusted linear regression. RESULTS: Plasma marine n-3 PUFA levels ranged from 2.7 to 20.3 wt%, with a median level of 7.7 wt% (interquartile range 4.3-11.1 wt%). High levels of plasma marine n-3 PUFAs were associated with lower serum triglycerides [Standardized regression coefficient (Std.ß-coeff.) - 0.14, p < 0.001], body mass index (Std. ß-coeff. -0.08, p < 0.001), serum creatinine (Std. ß-coeff. -0.03, p = 0.05), C-reactive protein levels (Std. ß-coeff. - 0.03, p = 0.04), higher levels of serum high-density lipoprotein cholesterol (Std. ß-coeff. 0.08, p < 0.001) and low-density lipoprotein cholesterol (Std. ß-coeff. 0.04, p = 0.003). High levels of plasma marine n-3 PUFAs were also associated with lower glycated hemoglobin (Std. ß-coeff. - 0.04, p = 0.01), however, only in individuals without diabetes. We found no associations between plasma marine n-3 PUFA levels and fasting plasma glucose or carotid intima-media thickness. High levels of plasma marine n-3 PUFAs were associated with higher educational level, more physical activity and lower prevalence of smoking. CONCLUSION: In this cross-sectional study of Norwegian individuals born in 1950, high levels of plasma marine n-3 PUFAs were favourably associated with several CV risk factors, suggesting that fish consumption might improve CV health.

Carotid Atherosclerosis and Cognitive Function in a General Population Aged 63-65 Years: Data from the Akershus Cardiac Examination (ACE) 1950 Study.

BACKGROUND: Studies on the relationship between carotid atherosclerosis and cognitive function in subjects from the general population are few and results have been inconsistent. OBJECTIVE: We aimed to investigate the association between carotid atherosclerotic burden and cognitive function in a cross-sectional analysis of a population-based cohort aged 63-65 years. METHODS: All habitants born in 1950 from Akershus County, Norway were invited to participate. A linear regression model was used to assess the association between carotid atherosclerosis and cognitive function. We used carotid plaque score as a measure of carotid atherosclerotic burden and the Montreal Cognitive Assessment (MoCA) for global cognitive function. RESULTS: We analyzed 3,413 individuals aged 63-65 with mean MoCA score 25.3±2.9 and 87% visible carotid plaques. We found a negative correlation between carotid plaque score and MoCA score (r = -0.14, p < 0.001), but this association was lost in multivariable analysis. In contrast, diameter or area of the thickest plaque was independently associated with MoCA score. Lower educational level, male sex, current smoking, and diabetes were also associated with lower MoCA score in multivariable analysis. CONCLUSION: Carotid atherosclerotic burden was, unlike other measures of advanced carotid atherosclerosis, not independently associated with global cognitive function.

Blood pressure at age 40 predicts carotid atherosclerosis two decades later: data from the Akershus Cardiac Examination 1950 Study.

OBJECTIVE: We assessed the impact of a single time-point measurement of SBP, DBP and pulse pressure at the age of 40, on carotid plaque burden, echolucent plaques and carotid intima-media thickness late midlife. METHODS: Individuals participating in two separate studies, 23 years apart, defined our cohort (n = 2714). 'The Age 40 Program', a nationwide Norwegian cardiovascular screening survey, performed 1985-1999, assessed cardiovascular risk factors and lifestyle variables at age 40. 'The ACE 1950 Study', a population-based cohort study on individuals born in 1950, performed 2012-2015, included ultrasound examinations of the carotid arteries. Blood pressure (BP) determinants of carotid atherosclerosis were assessed by regression models adjusted for cardiovascular risk factors at age 40, and late midlife BP. RESULTS: The participants, 50.3% women, had a mean age of 40 (SD 0.3) years in the first study, and 64 (SD 0.6) years in the second. At age 40, mean SBP was 128 (SD 14) mmHg, mean DBP was 78 (SD 10) mmHg and mean pulse pressure was 50 (SD 9) mmHg. SBP and DBP at age 40 predicted carotid plaque burden in late midlife. Only DBP predicted echolucent plaques, and none of the BP components predicted carotid intima-media thickness. CONCLUSION: A single time-point measurement of SBP and DBP at age 40 is associated with carotid plaque burden late midlife, also after adjustment for other cardiovascular risk factors at age 40, and of late midlife BP. Our findings emphasize the strong association between BP and atherosclerosis.

Prevalence of atrial fibrillation and cardiovascular risk factors in a 63-65 years old general population cohort: the Akershus Cardiac Examination (ACE) 1950 Study.

OBJECTIVES: To investigate the sex-specific prevalence of atrial fibrillation (AF), including subclinical AF found by screening in a general population aged 63-65 years. The prevalence of cardiovascular risk factors and their association with AF will also be investigated. DESIGN: Cross-sectional analysis of an observational, prospective, longitudinal, population-based cohort study. SETTING: General population in Akershus county, Norway. PARTICIPANTS: Women and men born in 1950. We included 3706 of 5827 eligible individuals (63.6%); 48.8% were women. METHODS: All participants underwent extensive cardiovascular examinations, including 12-lead ECG. History of AF and other cardiovascular diseases were self-reported. Subsequent validation of all reported or detected AF diagnoses was performed. RESULTS: Mean age was 63.9±0.7 years. Prevalence of ECG-verified AF was 4.5% (women 2.4%, men 6.4%; p<0.001), including screen-detected AF in 0.3% (women 0.1%, men 0.6%; p<0.01). Hypertension was found in 62.0% (women 57.8%, men 66.0%; p<0.001). Overweight or obesity was found in 67.6% (women 59.8%, men 74.9%; p<0.001). By multivariate logistic regression, risk factors associated with AF were height (OR 1.67 per 10 cm; 95% CI 1.26 to 2.22; p<0.001), weight (OR 1.15 per 10 kg; 95% CI 1.01 to 1.30; p=0.03), hypertension (OR 2.49; 95% CI 1.61 to 3.86; p<0.001), heart failure (OR 3.51; 95% CI 1.71 to 7.24; p=0.001), reduced estimated glomerular filtration rate (OR 2.56; 95% CI 1.42 to 4.60; p<0.01) and at least one first-degree relative with AF (OR 2.32; 95% CI 1.63 to 3.31; p<0.001), whereas male sex was not significantly associated (OR 1.00; 95% CI 0.59 to 1.68; p=0.99). CONCLUSION: In this cohort from the general population aged 63-65 years, we found a higher prevalence of known AF than previously reported below the age of 65 years. The additional yield of single time point screening for AF was low. Body size and comorbidity may explain most of the sex difference in AF prevalence at this age. TRIAL REGISTRATION NUMBER: NCT01555411; Results.

Prevalence of Carotid Plaque in a 63- to 65-Year-Old Norwegian Cohort From the General Population: The ACE (Akershus Cardiac Examination) 1950 Study.

BACKGROUND: New data on extracranial carotid atherosclerosis are needed, as improved ultrasound techniques may detect more atherosclerosis, the definition of plaque has changed over the years, and better cardiovascular risk control in the population may have changed patterns of carotid arterial wall disease and actual prevalence of established cardiovascular disease. We investigated the prevalence of atherosclerotic carotid plaques and carotid intima-media thickness (cIMT) and their relation to cardiovascular risk factors in a middle-aged cohort from the general population. METHODS AND RESULTS: We performed carotid ultrasound in 3683 participants who were born in 1950 and included in a population-based Norwegian study. Carotid plaque and cIMT were assessed according to the Mannheim Carotid Intima-Media Thickness and Plaque Consensus, and a carotid plaque score was used to calculate atherosclerotic burden. The participants were aged 63 to 65 years, and 49% were women. The prevalence of established cardiovascular disease was low (10%), but 62% had hypertension, 53% had hypercholesterolemia, 11% had diabetes mellitus, and 23% were obese. Mean cIMT was 0.73±0.11 mm, and atherosclerotic carotid plaques were present in 87% of the participants (median plaque score: 2; interquartile range: 3). Most of the cardiovascular risk factors, with the exception of diabetes mellitus, obesity and waist-hip ratio, were independently associated with the plaque score. In contrast, only sex, hypertension, obesity, current smoking, and cerebrovascular disease were associated with cIMT. CONCLUSIONS: We found very high prevalence of carotid plaque in this middle-aged population, and our data support a greater association between cardiovascular risk factors and plaque burden, compared with cIMT. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01555411.

Stroke Risk Is Low after Urgently Treated Transient Ischemic Attack.

BACKGROUND: Over the last decades, the approach to patients with transient ischemic attack (TIA) has shifted from treating only patients considered at high risk of recurrent stroke, to referring all patients with TIA to urgent assessment and immediate initiation of preventive treatment. The data on how this change has influenced the stroke rate after TIA are limited. Thus, the primary aim of this study was to identify the incidence of stroke recurrence after TIA. Second, we wanted to evaluate the ABCD2 score as a predictor of recurrent stroke. METHODS: Patients discharged with a diagnosis of TIA from the Stroke Unit at Akershus University Hospital between January 1, 2013 and December 31, 2013 were included in the study. Data were obtained from the electronic medical records. Readmission data to capture recurrent strokes were registered until December 31, 2015. RESULTS: In total, 261 patients were included. Mean age was 70.7 years. Stroke incidence at 1 month, 1 year, and the end of follow-up was 1.5% (n = 4), 3.4% (n = 9), and 4.2% (n = 11), respectively. Median time from TIA until recurrent stroke was 90 days. The ability of the ABCD2 score to predict recurrent stroke was low. CONCLUSIONS: Urgent admission of patients with TIA is followed by a very low risk of early and late recurrent stroke. The ABCD2 score did not identify patients at high risk of recurrent stroke.

Montreal Cognitive Assessment in a 63- to 65-year-old Norwegian Cohort from the General Population: Data from the Akershus Cardiac Examination 1950 Study.

AIMS: To investigate Montreal Cognitive Assessment (MoCA) test scores in a cohort aged 63-65 years from a general population in relation to the proposed cut-off score of 26 for mild cognitive impairment (MCI) and to explore the impact of education. METHODS: MoCA scores were assessed in the Akershus Cardiac Examination 1950 Study, a cross-sectional cohort study of all men and women born in 1950 living in Akershus County, Norway. The participants were aged 63-65 at the time of data collection. RESULTS: MoCA scores were available in 3,413 participants, of which 47% had higher education (>12 years). The mean MoCA score was 25.3 (95% confidence interval [CI] 25.2-25.4), and 49% had a score below the suggested cut-off of 26 points. Those with higher education had significantly higher scores (mean 26.2, 95% CI 26.1-26.3 vs. 24.4, 95% CI 24.3-24.6, p < 0.001). CONCLUSIONS: Approximately 50% scored below the cut-off score of 26 points, suggesting that the cut-off score may have been set too high to distinguish normal cognitive function from MCI. Educational level had a significant impact on MoCA scores.

Heart and Brain Interactions--the Akershus Cardiac Examination (ACE) 1950 Study Design.

OBJECTIVES: The aim of the Akershus Cardiac Examination (ACE) 1950 Study is to investigate the development and progression of cardiovascular and cerebrovascular disease (CVD/CeVD) in an extensively characterized age cohort of middle-aged subjects with longitudinal long-term follow-up. DESIGN: The ACE 1950 Study is a prospective, population-based, age-cohort study of all men and women born in 1950 in Akershus County, Norway. The study involves a comprehensive baseline examination, especially for CVD/CeVD, including advanced ultrasound imaging and biobanking ("deep phenotyping"). We expect to obtain an inclusion rate of > 60% from the total study population of 5,827 eligible subjects. Enrollment will be completed during 2015. CONCLUSIONS: The ACE 1950 Study will have potential to generate new and relevant insight into identification of subclinical disease progression. Extensive phenotyping will enable identification of novel disease markers and mechanisms for subclinical disease, which can prove important for future disease prevention.