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1.  Longitudinal Effects of a Decade of Aging on Carotid Artery Stiffness: The Multi-Ethnic Study of Atherosclerosis 
Background and Purpose
Arterial stiffening is associated with hypertension, stroke, and cognitive decline; however, the effects of aging and cardiovascular disease risk factors on carotid artery stiffening have not been assessed prospectively in a large multi-ethnic, longitudinal study.
Distensibility coefficient and Young’s elastic modulus of the right common carotid artery were calculated at baseline and after a mean (standard deviation) of 9.4 (0.5) years in 2,650 participants. Effects of age and cardiovascular disease risk factors were evaluated by multivariable mixed regression and analysis of covariance models.
At baseline, participants were 59.9 (9.4) years old (53% female; 25% Black, 22% Hispanic, 14% Chinese). Young’s elastic modulus increased from 1,581 (927) to 1,749 (1,306) mmHg (p<0.0001) and distensibility coefficient decreased from 3.1 (1.3) to 2.7 (1.1) x 10−3 mmHg−1 (p<0.001), indicating progressive arterial stiffening. Young’s elastic modulus increased more among participants who were >75 years old at baseline (p<0.0001). In multivariable analyses, older age and less education independently predicted worsening Young’s elastic modulus and distensibility coefficient. Stopping antihypertensive medication during the study period predicted more severe worsening of Young’s elastic modulus (β=360.2 mmHg, p=0.008). Starting antihypertensive medication after exam 1 was predictive of improvements in distensibility coefficient (β =1.1 x 10−4, mmHg−1; p=0.024).
Arterial stiffening accelerates with advanced age. Older individuals experience greater increases in Young’s elastic modulus than do younger adults, even after considering the effects of traditional risk factors. Treating hypertension may slow the progressive decline in carotid artery distensibility observed with aging and improve cerebrovascular health.
PMCID: PMC3888489  PMID: 24253542
Aging; Carotid arteries; Elasticity; Hypertension; Cardiovascular disease risk factors
2.  A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk 
PLoS ONE  2012;7(5):e36617.
Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. −0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26).In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk.
Trial Registration NCT00690417
Trial Registration NCT01049048
PMCID: PMC3346736  PMID: 22586483
3.  Long-Term Effects of Carotid Screening on Patient Outcomes and Behaviors 
Archives of internal medicine  2011;171(6):589-591.
PMCID: PMC3075090  PMID: 21444853
Atherosclerosis; Carotid arteries; Risk factors; Ultrasound
4.  Effects of an Office-Based Carotid Ultrasound Screening Intervention 
Carotid ultrasound screening (CUS) has been recommended for cardiovascular disease (CVD) risk prediction; however, its effectiveness in clinical practice is unknown. The purpose of this study was to prospectively determine the effects of office-based CUS on physician decision-making and patient health-related behaviors (HRBs).
Physicians from 5 non-academic, community practices recruited patients ≥40 years old with ≥1 CVD risk factor. Abnormal carotid ultrasound screening (AbnlCUS) was defined as carotid intima-media thickness >75th percentile or carotid plaque presence. Subjects completed questionnaires before and immediately after CUS, then 30 days later to determine self-reported behavioral changes. Odds ratios (OR) for changes in physician management and patient HRBs were determined from multivariate hierarchical logistic regression models.
There were 355 subjects (mean [standard deviation] 53.6 [7.9] years old, 2.3 [0.9] risk factors, 58% women); 266 (74.9%) had AbnlCUS. Presence of AbnlCUS altered physicians’ prescription of aspirin (p<0.001) and cholesterol medications (p<0.001). Immediately after CUS, subjects reported increased ability to change HRBs (p=0.002), regardless of their test results. Subjects with AbnlCUS reported increased CVD risk perception (OR 4.14, p<0.001), intentions to exercise (OR 2.28, p=0.008), make dietary changes (OR 2.95, p<0.001), and quit smoking (OR 4.98, p=0.022). After 30 days, 34% increased exercise frequency and 37% reported weight loss; but these changes were not predicted by the CUS results. AbnlCUS modestly predicted reduced dietary sodium (OR 1.45, p=0.002) and increased fiber (OR 1.55, p=0.022) intake.
Finding abnormal results on CUS had major effects on physician but not patient behaviors.
PMCID: PMC3279118  PMID: 21477989
Atherosclerosis; Carotid arteries; Risk factors; Ultrasound
5.  Effects of Smoking and Smoking Cessation on Endothelial Function: One-Year Outcomes from a Randomized Clinical Trial 
To determine if smoking cessation improves flow-mediated dilation (FMD) of the brachial artery (BA).
The long-term effects of continued smoking and smoking cessation on endothelial function have not been described previously.
This was a one-year, prospective, double-blind, randomized, placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies. FMD was measured by B-mode ultrasound before and 1-year after the target smoking cessation date. Cessation was verified by exhaled carbon monoxide levels. ΔFMD was compared among study arms and between subjects that successfully quit and those who continued to smoke. Predictors of baseline FMD and ΔFMD were identified by multivariable regression.
The 1,504 current smokers (58% female, 84% white) were mean (standard deviation): 44.7 (11.1) years old and smoked 21.4 (8.9) cigarettes/day. Baseline FMD was similar in each treatment arm (p=0.499) and was predicted by BA diameter (p<0.001), reactive hyperemia blood flow (p<0.001), high-density lipoprotein cholesterol (p=0.001), and carbon monoxide (p=0.012) levels. After one year, 36.2% quit smoking. FMD increased by 1% [6.2% (4.4%) to 7.2% (4.2%)] after 1 year (p=0.005) in those who quit, but did not change (p=0.643) in those who continued to smoke. Improved FMD among quitters remained significant (p=0.010) after controlling for changes in BA diameter, reactive hyperemia, low-density lipoprotein cholesterol, and presence of a home smoking ban.
Despite weight gain, smoking cessation leads to prolonged improvements in endothelial function, which may mediate part of the reduced cardiovascular disease risk observed after smoking cessation.
PMCID: PMC2947952  PMID: 20236788
Endothelial dysfunction; Clinical Trial; Risk Factors; Smoking
6.  Coronary Flow Velocity Changes in Response to Hypercapnia: Assessment by Transthoracic Doppler Echocardiography 
The effects of hypercapnia on coronary arteries in humans are not known. We used transthoracic Doppler echocardiography (TTDE) to evaluate coronary blood flow velocity (CFV) changes in response to hypercapnia in healthy adults.
Methods and Results
Twenty adults underwent TTDE of the left anterior descending coronary artery while breathing room air, 40% FiO2, and 40% FiO2 with CO2 supplemented to end-tidal tensions of +5, +7.5, and +10 mmHg above baseline. Mean (standard deviation) diastolic peak CFV values for these conditions were 23.1(9.1), 23.0(9.0), 25.5(9.3), 27.9(11.5), and 31.5(13.0) cm/s. Significant overall differences between conditions (p<0.001) and progressive levels of hypercapnia (p≤0.01) were observed. CFV increases remained significant after adjusting for increases in cardiac output (p=0.038).
CFV increases with hypercapnia. This is the first report of human coronary artery flow responses to hypercapnia. TTDE methodology is feasible for measuring CFV and the effects of hypercapnia on the coronary circulation.
PMCID: PMC1892636  PMID: 17400123
Blood flow; Coronary arteries; Carbon dioxide; Echocardiography

Results 1-6 (6)