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BACKGROUND AND AIMS: We assessed the predictive role of coronary artery calcification (CAC) in clinically relevant cognitive impairment in 148 middle-aged individuals with childhood-onset type 1 diabetes (TID) from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. METHODS: Baseline CAC was measured in 1996–98 and repeated 4–8 years later. Per extensive neuropsychological testing in 2010–15, 28% (41/148) of participants met the study definition of clinically relevant cognitive impairment (two or more of 7 select test scores ≥1.5SD worse than demographically appropriate published norms). Logistic regression models with backward selection were constructed for statistical analysis. RESULTS: Mean age and TID duration at first CAC measure were 37 and 29 years, respectively. A greater burden of initial CAC was associated with cognitive impairment determined 14 years later. Compared to Agatston score = 0, odds ratio (OR) and 95% confidence intervals (CI) of 0 < − 100, 100 < −300 and > 300 were 1.4 (0.6, 3.6), 2.3 (0.6, 9.7), and 7.9 (1.6, 38.5), respectively. With both initial and progression of CAC in the multivariable model, backward selection retained only CAC progression, showing it was significantly associated with cognitive impairment (OR [95% CI]: 1.7 [1.1, 2.9]). In those with an initial CAC > 0, CAC density was marginally, inversely, associated with cognitive impairment when controlling for CAC volume (OR [95%CI]: 0.3 (0.1, 1.2), p value = 0.078). CONCLUSIONS: Greater CAC burden was associated with clinically relevant cognitive impairment in middle-aged adults with childhood-onset TID. CAC progression appears to be a more powerful predictor than initial calcification.

Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men.We examined the association in 906 men aged 40-49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography.Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1-100 (n=411), 101-300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/s) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), P for trend0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group.The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40s.

Recent studies have shown that individuals with 0 coronary artery calcium (CAC) scores have very low risk of coronary heart disease. In the Healthy Women Study, we evaluated development of new CAC among postmenopausal women (n=272) over a 6 year period, age 62 at the 1st and 68 at the 3rd electron beam tomography (EBT) examination. At the 1st EBT, 155 of 272 (57%) women had 0 CAC. By the 3rd, 56 (36%) of these women had developed new CAC, including 38 with >5 Agatston units. There was practically no regression from having CAC at with the 1st EBT to no CAC at the 3rd EBT. The risk of developing new CAC over 6 years among women with 0 CAC on their 1st EBT was strongly and significantly related to presence of both aortic calcium and carotid plaque at the time of 1st EBT. Baseline premenopausal risk factors, age 47, apolipoprotein B, body mass index (BMI) and triglycerides, were significant predictors of incident CAC as were the changes in BMI and low density lipoprotein cholesterol between premenopause and the 1st post exam, age 53. Risk factors measured premenopause and change in risk factors from premenopause to the 1st post exam and the extent of subclinical disease in other vascular beds are primary determinants of the risk of developing incident CAC in women over a 6 year period.

Race-specific data for the association between coronary artery calcification (CAC) and carotid intimal medial thickness (IMT) are limited. We sought to compare black-white specific associations of these two measures.We conducted a population-based study of 379 randomly selected men aged 40-49 years (84 black and 295 white) from Allegheny County, US (2004-2006). Agatston CAC score was evaluated by electron-beam tomography and carotid IMT was evaluated by ultrasonography.Compared to white men, black men had similar prevalence of CAC (p=0.56) and higher total carotid IMT (p0.001). In black and white men, CAC score had significant positive correlations with total carotid IMT (r=0.47 and r=0.24, respectively, p0.001 for both) as well as the IMT for the common carotid artery (CCA), internal carotid artery and carotid bulb. The associations of CAC with total and CCA IMT were significantly stronger in black (beta=0.07 and beta=0.05, respectively) than white men (beta=0.03 and beta=0.01, respectively) after adjustment for traditional coronary risk factors (p=0.046 and p=0.036, respectively).In black and white middle aged men, CAC score had significant positive correlations with total and segmental carotid IMT. CAC was more predictive of total and CCA IMT in black than white men independent of coronary risk factors.

The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than LDL cholesterol (LDLC), total LDL particles and usual measurement of oxidized LDL. The association between LAB and intima-media thickness (IMT) of carotid artery was investigated by ultrasound in US and Japan men.Participants were 297 US Caucasian and 310 Japanese men, aged 40-49 years without past history of cardiovascular disease. Serum LAB levels were measured by ELISAs with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody.Serum LAB levels [median (interquartile range), μg/L] were 1321 (936, 1730) in US Caucasians and 940 (688, 1259) in Japanese. For Caucasian men, average IMT was higher in higher LAB quartile, which was 0.653, 0.667, 0.688, and 0.702 mm, respectively (p for trend = 0.02). Linear regression analysis showed serum LAB was significantly associated with IMT after adjustment for LDLC or total LDL particles in addition to other traditional or novel risk factors for atherosclerosis such as C-reactive protein. However, there was no significant relationship between LAB and IMT in Japanese men.Serum LAB, a new candidate biomarker for residual risk, was associated with an increased carotid IMT in US Caucasian men independently of various risk factors; however, ethnic difference should be clarified in the future.

The Healthy Women Study has evaluated risk factor changes as women go through the menopause. In 274 women, measures of atherosclerosis in the coronary, aorta and carotid arteries were obtained at 8 years postmenopause using electron beam tomography and carotid ultrasound. The purpose of this study was to evaluate the association between baseline premenopausal risk factors and subclinical disease in various vascular beds and with an aggregate atherosclerosis index based on all subclinical measures. The prevalence of measurable disease for the coronaries, carotids and aorta was 45, 55 and 72%, respectively. Disease measures across these three locations were significantly correlated (P