Greater Aortic Calcification Research Articles

An investigation of the relationship between tumor location and survival following colon cancer resection.

255 Background: Both tumour location and systemic inflammation (SI) have been related to survival in patients undergoing curative surgery for colon cancer. Recently, right colon cancer (RCC) has been associated with pre-existing cardiovascular disease (CVD). Comorbidity scores such as the Lee Cardiac Risk Index (LCRI) capture symptomatic disease only. Imaging-based assessment of vascular calcification can be used to identify subclinical CVD. We explored the relationship between tumour location, systemic inflammation, cardiac comorbidity and survival in patients undergoing CC resection. Methods: Patients were identified from a prospective cancer database. Clinicopathological characteristics and survival data were abstracted. Aortic calcification (AC) was quantified visually on staging CT images. SI was measured using the modified Glasgow Prognostic Score (mGPS). Results: Of 418 patients, most were female (221, 53%), over 65 (282, 67%), ASA grade II or less (66%) with RCC (230, 55%) and TNM II-III disease (320, 77%). Compared with LCC, RCC was associated with increasing age (59% vs 41%, p = 0.039), greater AC (61% vs 39%, p = 0.013) but not SI (61% vs 39%, p = 0.139). There were no significant differences between LCC with respect to ASA, smoking status or LCRI. Univariate analysis revealed TNM stage (HR 3.55 (95%CI 1.51 - 8.39) p = 0.004) and degree of AC (HR 1.77 (1.04 - 3.00) p = 0.034) were associated with cancer-specific survival (CSS) in RCC while in LCC, only TNM stage was related to CSS (HR 2.30 (0.99 - 5.30) p = 0.05). Multivariate analysis in patients with RCC confirmed AC to be a stage-independent predictor of CSS (HR 1.94 (1.15 – 3.67) p = 0.013). Conclusions: AC is associated with RCC and confers an inferior prognosis, independent of stage. Investigation of underlying mechanisms is required, but impaired perfusion may limit mucosal function, potentiating the effect of carcinogens in the right colon.

Abstract P119: Changes in Cholesterol Efflux Capacity are Associated With Greater Progression of Aortic Calcification in Women at Midlife. Effects of Estradiol, Metabolic and Inflammatory Status

Objective: High-density lipoprotein cholesterol efflux capacity (HDL-CEC) is associated inversely with CVD events. Recently, unexpected increases inHDL-CEC have been reported early after menopause. However, associations between HDL-CEC early changes and atherosclerotic progression in midlife women are not clear. We aimed to 1) test whether HDL-CEC changes from before to after menopause are associated with coronary (CAC) and aortic calcification (AC) progression anchored to the final menstrual period (FMP) date and 2) assess whether these associations could be explained by: time-varying estradiol, insulin resistance index (HOMA-IR), or C-reactive protein (CRP). Methods: Participants were fromthe Pittsburgh site of the Study of Women’s Health Across the Nation (SWAN). HDL-CEC and calibrated ion mobility HDL particles (HDL-Ps) were measured at two time points: one before and one after menopause (median time difference=6 Yr) and change in each metric was calculated as the difference between the two assessments. CAC and AC Agatston scores were available at the 2 nd time point (after menopause) and 2.08 Yr (median time difference) before that. Participants were not on lipid lowering medications or hormone therapy. Linear mixed effect models of repeated measures of log (AC+1) or log (CAC+1) as a function of within-woman change in HDL-CEC, race, time-varying BMI, time since 1 st calcification assessment and time before/after FMP were used. Progression of calcification per 1 year increase before/after FMP for every 1 unit increase in log HDL-CEC change were estimated by adding interaction between log HDL-CEC change and time before/after FMP to the above specified model. Estradiol, HOMA-IR, or CRP was added one at a time to the final models. Results: We studied 33 women (66 observations) (67% White and 33% Black) aged 52±2.3 Yr who were either peri- (64%) or postmenopause (36%) at calcification 1 st measure. At calcification 2 nd measure, all women were postmenopausal with a median time before/after FMP = 2.81 (Q1:1.84, Q3:4.30) Yr. Higher HDL-CEC change was associated with greater AC progression per 1 year increase before/after FMP (β(SE): 2.23(0.90) for every 1 log unit higher in HDL-CEC change, P =0.02). This association remained significant after adjusting for premenopausal HDL-CEC level, or changes in HDL-C or HDL-Ps. However, adjusting for estradiol, HOMA-IR, or CRP, the positive association between HDL-CEC and AC progression was largely attenuated and no longer significant. HDL-CEC changes were not associated with CAC progression. Conclusions: In this pilot study, increases in HDL-CEC early after menopause were associated with greater AC progression that was largely explained by midlife hormonal, metabolic or inflammation status. The midlife is a critical period that could impact HDL function and thus its cardio-protective effects. Our results should be retested in a larger setting.

Abstract P327: Associations Between Ectopic Cardiovascular Fat Depots and Aortic Calcification Vary by Race and Menopausal Status in Women at Midlife: The Study of Women’s Health Across the Nation (SWAN) Ectopic Cardiovascular Fat Ancillary Study

Objective: Mounting evidence demonstrates a role of ectopic cardiovascular fat (ECF), which surrounds the heart and vasculature, in the pathogenesis of cardiovascular disease (CVD). It is unknown whether ECF depots are related to atherosclerotic burden in women transitioning through menopause, a time of increasing CVD risk. We evaluated the cross-sectional associations between volumes of epicardial (EAT), pericardial (PAT), total heart (TAT; TAT=EAT+PAT) and perivascular (peri-aortic) (PVAT) adipose tissues and aortic calcification (AC) in a sample of white and black midlife women. Effect modifications by race and menopausal status were also examined. Design: Data were obtained from the SWAN ectopic cardiovascular fat ancillary study. AC and ECF depots were quantified by electron beam computed tomography. Outcomes were presence of AC among all women, and extent of AC among women with an Agatston score >0. Logistic and linear regression were used as appropriate. Final models were adjusted for age, race, study site, menopausal status, body mass index (BMI), systolic blood pressure, lipids and insulin resistance. Results: The study included 257 women (32.7% Black; 58.7% pre-/early peri-menopausal and 41.3% late peri-/postmenopausal) aged 46-58 years with data on any of the 4 ECF depots (EAT, PAT and TAT: n=227, PVAT: n=191). AC was found in 184 (71.6%) participants. Pre-/early peri menopausal women had less EAT (median (Q1, Q3): 35.0 (28.4, 51.7) cm 3 vs. 43.5 (32.9, 58.3) cm 3 , P = 0.02) and TAT (median (Q1, Q3): 42.5 (33.2, 64.5) cm 3 vs. 50.3 (38.9, 74.3) cm 3 , P = 0.05) than late peri-/postmenopausal women, respectively. In final models, only EAT (OR (95%CI): 3.29 (1.14, 9.54)) was associated with higher odds of presence of AC. Interactions with race or menopausal status were not significant. Relationships between ECF depots (EAT,PAT and TAT) and extent of AC varied by race (all P <0.05); in that higher volumes of EAT, PAT and TAT were associated with greater AC in black compared with white women in final models. Irrespective of race or menopausal status, higher volumes of PVAT (β (SE): 1.60 (0.63), P= 0.01, per 1 log-unit increase in PVAT) were associated with greater extent of AC in the fully adjusted model. In black women only, the associations of PAT and TAT with extent of AC varied by menopausal status (all P <0.05) independent of age, BMI and other CVD risk factors: late peri-/postmenopausal women had significantly more AC than pre-/early peri-menopausal women for each 1-log unit increase in PAT (β (SE): 1.57 (0.66), P=0.02) and TAT (β (SE): 2.29 (1.04), P=0.03). Conclusion: ECF depots are associated with aortic calcification in women at midlife and the associations vary by race and menopausal status. Perhaps ECF plays a role in the higher risk of CVD reported in women after menopause.

Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model

Increased aortic pulse-wave velocity (PWV) reflects increased arterial stiffness and is a strong predictor of cardiovascular risk in chronic kidney disease (CKD). We examined functional and structural correlations among PWV, aortic calcification, and vascular remodeling in a rodent model of CKD, the Lewis polycystic kidney (LPK) rat. Hemodynamic parameters and beat-to-beat aortic PWV were recorded in urethane-anesthetized animals [12-wk-old hypertensive female LPK rats (n = 5)] before the onset of end-stage renal disease and their age- and sex-matched normotensive controls (Lewis, n = 6). Animals were euthanized, and the aorta was collected to measure calcium content by atomic absorption spectrophotometry. A separate cohort of animals (n = 5/group) were anesthetized with pentobarbitone sodium and pressure perfused with formalin, and the aorta was collected for histomorphometry, which allowed calculation of aortic wall thickness, medial cross-sectional area (MCSA), elastic modulus (EM), and wall stress (WS), size and density of smooth muscle nuclei, and relative content of lamellae, interlamellae elastin, and collagen. Mean arterial pressure (MAP) and PWV were significantly greater in the LPK compared with Lewis (72 and 33%, respectively) animals. The LPK group had 6.8-fold greater aortic calcification, 38% greater aortic MCSA, 56% greater EM/WS, 13% greater aortic wall thickness, 21% smaller smooth muscle cell area, and 20% less elastin density with no difference in collagen fiber density. These findings demonstrate vascular remodeling and increased calcification with a functional increase in PWV and therefore aortic stiffness in hypertensive LPK rats.

CT Emphysema Predicts Thoracic Aortic Calcification in Smokers with and Without COPD

ABSTRACTCOPD patients are at increased risk for cardiovascular morbidity and mortality independent of smoking habits. Recent studies suggest CT emphysema is an independent predictor of cardiovascular risk as evidenced by its association with arterial stiffness and impaired endothelial function. We examined the relationship between demographics, lung function, CT emphysema and airway wall thickness and thoracic aortic calcification, another marker of cardiovascular risk, in the National Lung Screening Trial. We hypothesized that CT emphysema would be independently associated with thoracic aortic calcification. Two hundred forty current and former smokers were enrolled. After CT examination, we recorded subjects’ demographics and they performed spirometry. Subjects were classified into COPD and non-COPD subgroups. CT emphysema was quantified as a percentage of lung volume and measurements of the right upper lobe airway were performed using standard methods and expressed as wall area (%). Total calcification scores for the thoracic aorta were computed using TeraRecon image analysis. Univariate and multivariate analyses were performed to determine the associations between calcium score and subject characteristics. Subjects with COPD were older, more often male, heavier smokers and had more CT emphysema and greater aortic calcification than those without COPD. Calcium score was associated with age, pack-years, CT emphysema, wall area%, and lung function on univariate testing but only with age and CT emphysema on multivariate analysis. We conclude that CT emphysema is independently associated with thoracic calcification and thus may be used to assess cardiovascular risk in smokers with and without COPD.

Hot Flashes and Subclinical Cardiovascular Disease

Although evidence suggests adverse vascular changes among women with hot flashes, it is unknown whether hot flashes are associated with subclinical cardiovascular disease. The aim of this study was to examine relations between menopausal hot flashes and indices of subclinical cardiovascular disease. We hypothesized that women with hot flashes would show reduced flow-mediated dilation and greater coronary artery and aortic calcification compared with women without hot flashes. The Study of Women's Health Across the Nation Heart Study (2001 to 2003) is an ancillary study to the Study of Women's Health Across the Nation, a community-based cohort study. Participants were 492 women (35% black, 65% white) 45 to 58 years of age who were free of clinical cardiovascular disease and had a uterus and at least 1 ovary. Measures included a brachial artery ultrasound to assess flow-mediated dilation, electron beam tomography to assess coronary artery and aortic calcification, reported hot flashes (any/none, previous 2 weeks), and a blood sample for measurement of estradiol concentrations. Cross-sectional associations were evaluated with linear regression and partial proportional odds models. Hot flashes were associated with significantly lower flow-mediated dilation (beta=-1.01; SE, 0.41; P=0.01) and greater coronary artery (odds ratio, 1.48; 95% confidence interval, 1.04 to 2.12) and aortic (odds ratio, 1.55; 95% confidence interval, 1.10 to 2.19) calcification in age- and race-adjusted models. Significant associations between hot flashes and flow-mediated dilation (beta=-0.97; SE, 0.44; P=0.03) and aortic calcification (odds ratio, 1.63; 95% confidence interval, 1.07 to 2.49) remained in models adjusted for cardiovascular disease risk factors and estradiol. Women with hot flashes had reduced flow-mediated dilation and greater aortic calcification. Hot flashes may mark adverse underlying vascular changes among midlife women.