Coronary arteries are the blood vessels supplying oxygen-rich blood to the heart muscles. Coronary artery calcium (CAC), which is the total amount of calcium deposited in these arteries, indicates the presence or the future risk of coronary artery diseases. Quantification of CAC is done by using computed tomography (CT) scan which uses attenuation of x-ray by different tissues in the body to generate three-dimensional images. Calcium can be easily spotted in the CT images because of its higher opacity to x-ray compared to that of the surrounding tissue. However, the arteries cannot be identified easily in the CT images. Therefore, a second scan is done after injecting a patient with an x-ray opaque dye known as contrast material which makes different chambers of the heart and the coronary arteries visible in the CT scan. This procedure is known as computed tomography angiography (CTA) and is performed to assess the morphology of the arteries in order to rule out any blockage in the arteries. The CT scan done without the use of contrast material (non-contrast-enhanced CT) can be eliminated if the calcium can be quantified accurately from the CTA images. However, identification of calcium in CTA images is difficult because of the proximity of the calcium and the contrast material and their overlapping intensity range. In this dissertation first we compare the calcium quantification by using a state-of-the-art non-contrast-enhanced CT scan method to conventional methods suggesting optimal quantification parameters. Then we develop methods to accurately quantify calcium from the CTA images. The methods include novel algorithms for extracting centerline of an artery, calculating the threshold of calcium adaptively based on the intensity of contrast along the artery, calculating the amount of calcium in mixed intensity range, and segmenting the artery and the outer wall. The accuracy of the calcium quantification from CTA by using our methods is higher than the non-contrast-enhanced CT thus potentially eliminating the need of the non-contrast-enhanced CT scan. The implications are that the total time required for the CT scan procedure, and the patient's exposure to x-ray radiation are reduced.

Objective: To examine the association between subclinical atherosclerosis (ascertained as coronary artery calcium; CAC) in asymptomatic individuals in the Central Appalachian region of the United States and individual- and geographic-level factors. Methods: Data were obtained from participants in CAC screening during 2012 and 2016. CAC score was assessed as CAC=0 (no plaque), 1≤CAC≤99 (mild plaque), 100≤CAC≤399 (moderate plaque), and CAC≥400 (severe plaque). Additionally, data on demographics (age, sex, and race), medical conditions, lifestyle factors, and family history of coronary artery disease (CAD) were obtained. Further, zip codes of place of residence for participants were used to generate geographic-level data. Descriptive statistics were used to estimate the prevalence of CAC, and multinomial logistic regression models were used to delineate significant factors. Results: Of 1512 participants, 57.6% had CAC>0. The prevalence of mild, moderate, and severe plaques was 31.6%, 16.3%, and 9.7%, respectively. Demographic, medical conditions, lifestyle factors, and family history of CAD were associated with increased risk for subclinical atherosclerosis. Further, the proportion of minority residents significantly increased the risk for severe plaque [RRR=1.06; p-value=0.04] and the proportion of residents on government assistance significantly decreased the risk for mild plaque [RRR=0.93; p-value=0.03]. Conclusion: The results imply that the proportion of minority residents in a geographic area is associated with increased relative risk for subclinical atherosclerosis, while the proportion of residents on government assistance decreased such risk. However, future geographic or neighborhood-level studies with larger sample size are needed to delineate further the consistency of these results in the Central Appalachian population.

INTRODUCTION: The risk factors for cardiovascular disease (CVD) are associated with coronary atherosclerosis and having multiple risk factors potentiates atherosclerosis. This study examined the prevalence of multiple biological and lifestyle/behavioral risk factors and their association with coronary artery calcium (CAC), a marker for subclinical coronary atherosclerosis. METHODS: This is a cross-sectional study of 1607 community-dwelling asymptomatic individuals from central Appalachia who participated in CAC screening between January 2011 and December 2012. Data on demographics (sex and age) and 7 traditional risk factors for coronary artery disease (CAD) were collected and categorized into 5 groups (0-1, 2, 3, 4, and ≥5). Prevalence of these risk factors and CAC scores (0, 1-99, 100-399, ≥400) were assessed, and the impact of the number of risk factors on CAC scores were delineated using multiple logistic regression. RESULTS: Over 98% of participants had ≥1 risk factor. While obesity, diabetes, hypertension, and family history of CAD significantly increased the odds of having CAC, CAC scores significantly increased with number of risk factors. After adjusting for demographic factors, having 3, 4, and ≥5 risk factors was significantly associated with increased odds of having higher CAC scores when compared to zero CAC score by more than one and half times [OR=1.65, CI (1.20-2.25)], two times [OR=2.32, CI (1.67-3.23)] and three times [OR=3.45, CI (2.42-4.92)], respectively. CONCLUSION: The high prevalence of multiple risk factors in the study population suggests the need for aggressive multiple risk factors interventions for primary prevention of CAD, which could address CVD health disparities.

Aim: To examine the association of cardiovascular disease risk factors with and their cumulative effect on coronary artery calcium in hard-to-reach asymptomatic patients with diabetes. Methods: : A total of 2563 community-dwelling asymptomatic subjects from Central Appalachia participated in coronary artery calcium screening at a heart centre. Binary variable was used to indicate that coronary artery calcium was either present or absent. Independent variables consisted of demographic and modifiable risk factors and medical conditions. Descriptive statistics and multinomial logistic regression analyses were conducted. Results: : In total, 55.8% and 13.7% of study participants had subclinical atherosclerosis (coronary artery calcium ⩾1) and diabetes, respectively. The presence of coronary artery calcium was higher in subjects with diabetes (68.5%) than those without (53.8%). Compared to subjects without diabetes with coronary artery calcium = 0, obesity, hypertension, hypercholesterolaemia and smoking increased the odds of the presence of coronary artery calcium (coronary artery calcium score ⩾1) regardless of diabetes status; however, with larger odds ratios in subjects with diabetes. Compared to subjects without diabetes with coronary artery calcium score = 0, having 3, 4 and ⩾5 risk factors increased the odds of presence of coronary artery calcium in subjects with diabetes by 14.06 (confidence interval = 3.26–62.69), 32.30 (confidence interval = 7.41–140.82) and 47.12 (confidence interval = 10.35–214.66) times, respectively. Conclusion: : There is a need for awareness about subclinical atherosclerosis in patients with diabetes and more research about coronary artery calcium in subpopulations of patients.

Aim To examine the risk factor of coronary artery calcium (CAC) in individuals with diabetes and those without diabetes in Central Appalachia. Methods Study population included 2479 asymptomatic participants who underwent CAC screening between August 2012 and November 2016. CAC score was classified into four categories [0 (no plaque), 1–99 (mild plaque), 100–399 (moderate plaque), and ≥400 (severe plaque)]. Multinomial logistic regression analyses were conducted to test the association between CAC and cardiovascular disease (CVD) risk factors among participants with diabetes, age and gender matched controls, and randomly selected controls. Results 13.6% of total participants had diabetes. Around 69%, 59.8%, and 57.7% of the participants with diabetes, matched controls, and randomly selected controls had CAC score ≥1, respectively. Participants with diabetes had higher prevalence of all CVD risk factors than controls. Among participants with diabetes, hypertension and physical inactivity increased the odds of CAC = 100–399, while among those without diabetes, hypertension and hypercholesteremia increased the odds of having CAC = 1–99 and CAC ≥ 400. Conclusion Half of study participants had subclinical atherosclerosis (i.e., CAC), and individuals with diabetes had higher CAC scores. This study suggests that individuals with diabetes in Central Appalachia might benefit from screening for CAC.

Background: Annually, over 150,000 cardiovascular events occur among individuals ,65 years old in the United States, including asymptomatic ones. Coronary artery calcium (CAC), a subclinical marker of coronary artery disease (CAD), enhances risk stratification among asymptomatic individuals. This study assessed the prevalence of CAC in a rural population and determined relationships between traditional risk factors for CAD and CAC scores. Methods: During January 2011 to December 2012, asymptomatic individuals from central Appalachia were screened for CAC in the largest tertiary cardiovascular institute. Based on Agatston scale, participants were grouped into 4 CAC scores: zero (CAC 5 0), mild (CAC 5 1-99), moderate (CAC 5 100-399) and severe (CAC $ 400). Multinomial logistic regression was used to examine associations between potential risk factors of CAD and CAC score. Results: Of 1,674 participants, 55.4% had positive CAC score (CAC . 0). Increasing age and being male were positively associated with higher CAC scores. Although there was significant association between mild CAC and hypertension and family history of CAD, moderate CAC was positively associated with smoking status. Except hypercholesterolemia and sedentary lifestyle, severe CAC was significantly associated with major health conditions (obesity, diabetes and hypertension), lifestyle (smoking) and family history of CAD. Conclusions: More than half of participants in the CAC screening had subclinical CAD (CAC score . 0). The association between CAC score and CAD risk factors suggests that education about subclinical atherosclerosis among asymptomatic individuals in this region with high cardiovascular disease prevalence is needed because CAC improves CAD risk stratification, and the knowledge of CAC enhances medication adherence and motivates individuals towards beneficial behavioral/lifestyle modification.

The objectives of this thesis are: a) To examine racial/ethnic differences in coronary artery calcification (CAC) and CAD, between symptomatic South Asians and Caucasians, matched for age, gender and conventional cardiovascular risk factors, b) To assess, using a meta-analysis model, the natural history of and stability of measurements of coronary artery calcium scoring (CACs) based on data collected from two large published trials: St Francis and EBEAT, c) To investigate the prevalence of coronary artery calcification in individuals with CT evidence for AVC, mitral valve calcification (MAC) or of both of them (AVC+MAC), d) To assess any potential association between premature CAD (<55 years in first-degree male relatives and <65 years in first-degree female relatives) and CAC in a large cohort of asymptomatic individuals. We found that coronary artery calcification is more extensive and diffuse in symptomatic patients of South Asian ethnic origin as compared to Caucasians, despite similar conventional risk factors for CAD. This is more evident in those >50 years of age, suggesting potential genetic or other risk factors yet to be determined. The natural history of coronary artery calcification was overtime progression in the majority of subjects, irrespective of gender. The higher variability in RCA measurements could be related to the low baseline CACs or exaggerated movement of the right side atrioventricular ring, whereas those for LCA brances are influenced by the branch allocation of the CACs. Valve calcification is not isolated but involve also and the coronary arteries. The presence of calcification in the aortic valve or combined aortic and mitral valves predicted coronary artery calcification. Additionally patients in whom both valves have become calcified tend to have severe coronary artery calcification. And finally, there is no relationship between the prevalence and extent of coronary artery calcification and the presence of family history of coronary heart disease in asymptomatic individuals with none of the conventional risk factors for atherosclerosis.

INTRODUÇÃO. Estudos de qualidade variável mostram maior prevalência de doença cardiovascular e de marcadores de aterosclerose em tabagistas com doença pulmonar obstrutiva crônica (DPOC) em relação a tabagistas sem a doença. OBJETIVOS. Verificar se escore de cálcio coronariano (ECC) elevado e anormalidade do índice tornozelo-braquial (ITB) são mais prevalentes em tabagistas pesados com DPOC do que sem DPOC, e se proteína C reativa sérica (PCR) e volume expiratório forçado no primeiro segundo em relação ao previsto (VEF1%) se correlacionam com ECC e ITB em tabagistas com e sem DPOC. POPULAÇÃO E MÉTODOS. Foram incluídos indivíduos consecutivos com carga tabágica @ 20 maços-ano. Os pacientes foram divididos em grupo 1 (com DPOC) e grupo 2 (assintomáticos respiratorios com espirometria normal). Coletaram-se dados clínicos, laboratoriais e antropométricos e determinados ECC, ITB e PCR sérica. Comparouse a prevalência de ECC acima do percentil 75 e de ITB anormal entre os grupos, e verificou-se a correlação entre PCR, ECC e ITB e entre VEF1%, ECC e ITB. / BACKGROUND. Studies of various quality levels show higher prevalence of cardiovascular disease and atherosclerosis markers in smokers with chronic obstructive pulmonary disease (COPD) compared to smokers without the disease. OBJECTIVES. The aims of this study were, firstly, to verify whether an elevated coronary calcium score (CCS) and abnormal ankle-brachial index (ABI) are more prevalent in heavy smokers with COPD than in those without COPD, and secondly, to investigate whether serum C-reactive protein (CRP) and predicted forced expiratory volume in the first second (FEV1%) are correlated with CCS and ABI in smokers with and without COPD. METHODS. We included clinically stable consecutive individuals with smoking history of @ 20 pack-years and COPD (group 1) or normal spirometry (group 2). Clinical, laboratory and anthropometric data were collected and CCS, ABI and serum CRP were measured. We compared the prevalence of CCS above the 75th percentile and the rates of abnormal ABI in both groups. Additionally, the correlation between CRP, CCS and ABI and FEV1%, CCS, and ABI was determined.

INTRODUÇÃO. Estudos de qualidade variável mostram maior prevalência de doença cardiovascular e de marcadores de aterosclerose em tabagistas com doença pulmonar obstrutiva crônica (DPOC) em relação a tabagistas sem a doença. OBJETIVOS. Verificar se escore de cálcio coronariano (ECC) elevado e anormalidade do índice tornozelo-braquial (ITB) são mais prevalentes em tabagistas pesados com DPOC do que sem DPOC, e se proteína C reativa sérica (PCR) e volume expiratório forçado no primeiro segundo em relação ao previsto (VEF1%) se correlacionam com ECC e ITB em tabagistas com e sem DPOC. POPULAÇÃO E MÉTODOS. Foram incluídos indivíduos consecutivos com carga tabágica @ 20 maços-ano. Os pacientes foram divididos em grupo 1 (com DPOC) e grupo 2 (assintomáticos respiratorios com espirometria normal). Coletaram-se dados clínicos, laboratoriais e antropométricos e determinados ECC, ITB e PCR sérica. Comparouse a prevalência de ECC acima do percentil 75 e de ITB anormal entre os grupos, e verificou-se a correlação entre PCR, ECC e ITB e entre VEF1%, ECC e ITB. / BACKGROUND. Studies of various quality levels show higher prevalence of cardiovascular disease and atherosclerosis markers in smokers with chronic obstructive pulmonary disease (COPD) compared to smokers without the disease. OBJECTIVES. The aims of this study were, firstly, to verify whether an elevated coronary calcium score (CCS) and abnormal ankle-brachial index (ABI) are more prevalent in heavy smokers with COPD than in those without COPD, and secondly, to investigate whether serum C-reactive protein (CRP) and predicted forced expiratory volume in the first second (FEV1%) are correlated with CCS and ABI in smokers with and without COPD. METHODS. We included clinically stable consecutive individuals with smoking history of @ 20 pack-years and COPD (group 1) or normal spirometry (group 2). Clinical, laboratory and anthropometric data were collected and CCS, ABI and serum CRP were measured. We compared the prevalence of CCS above the 75th percentile and the rates of abnormal ABI in both groups. Additionally, the correlation between CRP, CCS and ABI and FEV1%, CCS, and ABI was determined.

INTRODUÇÃO. Estudos de qualidade variável mostram maior prevalência de doença cardiovascular e de marcadores de aterosclerose em tabagistas com doença pulmonar obstrutiva crônica (DPOC) em relação a tabagistas sem a doença. OBJETIVOS. Verificar se escore de cálcio coronariano (ECC) elevado e anormalidade do índice tornozelo-braquial (ITB) são mais prevalentes em tabagistas pesados com DPOC do que sem DPOC, e se proteína C reativa sérica (PCR) e volume expiratório forçado no primeiro segundo em relação ao previsto (VEF1%) se correlacionam com ECC e ITB em tabagistas com e sem DPOC. POPULAÇÃO E MÉTODOS. Foram incluídos indivíduos consecutivos com carga tabágica @ 20 maços-ano. Os pacientes foram divididos em grupo 1 (com DPOC) e grupo 2 (assintomáticos respiratorios com espirometria normal). Coletaram-se dados clínicos, laboratoriais e antropométricos e determinados ECC, ITB e PCR sérica. Comparouse a prevalência de ECC acima do percentil 75 e de ITB anormal entre os grupos, e verificou-se a correlação entre PCR, ECC e ITB e entre VEF1%, ECC e ITB. / BACKGROUND. Studies of various quality levels show higher prevalence of cardiovascular disease and atherosclerosis markers in smokers with chronic obstructive pulmonary disease (COPD) compared to smokers without the disease. OBJECTIVES. The aims of this study were, firstly, to verify whether an elevated coronary calcium score (CCS) and abnormal ankle-brachial index (ABI) are more prevalent in heavy smokers with COPD than in those without COPD, and secondly, to investigate whether serum C-reactive protein (CRP) and predicted forced expiratory volume in the first second (FEV1%) are correlated with CCS and ABI in smokers with and without COPD. METHODS. We included clinically stable consecutive individuals with smoking history of @ 20 pack-years and COPD (group 1) or normal spirometry (group 2). Clinical, laboratory and anthropometric data were collected and CCS, ABI and serum CRP were measured. We compared the prevalence of CCS above the 75th percentile and the rates of abnormal ABI in both groups. Additionally, the correlation between CRP, CCS and ABI and FEV1%, CCS, and ABI was determined.