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2017

Accuracy of low-density lipoprotein cholesterol estimation at very low levels

Quispe, R., Hendrani, A., Elshazly, M. B., Michos, E. D., McEvoy, J. W., Blaha, M. J., Banach, M., Kulkarni, K. R., Toth, P. P., Blumenthal, R. S., Jones, S. R. & Martin, S. S. Apr 20 2017 In : BMC Medicine. 15, 1, 83

Research output: Research - peer-reviewArticle

LDL Cholesterol
Ultracentrifugation
Safety
VLDL Cholesterol
Practice Guidelines
Coronary Vessels
Guidelines
Calcium
Cost-Benefit Analysis
Radiation

Associations of Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events

Miller, P. E., Zhao, D., Frazier-Wood, A. C., Michos, E. D., Averill, M., Sandfort, V., Burke, G. L., Polak, J. F., Lima, J. A. C., Post, W. S., Blumenthal, R. S., Guallar, E. & Martin, S. S. Feb 1 2017 In : American Journal of Medicine. 130, 2, p. 188-197.e5

Research output: Research - peer-reviewArticle

Coffee
Tea
Caffeine
Coronary Vessels
Calcium

Beyond the headlines

Whelton, S. P. & Blumenthal, R. S. Jan 3 2017 In : Circulation. 135, 1, p. 3-4 2 p.

Research output: Research - peer-reviewShort survey

Precision Medicine
Angiography
Lipids
Therapeutics
Aptitude

Evaluating the atherogenic burden of individuals with a Friedewald-estimated low-density lipoprotein cholesterol <70 mg/dL compared with a novel low-density lipoprotein estimation method

Whelton, S. P., Meeusen, J. W., Donato, L. J., Jaffe, A. S., Saenger, A., Sokoll, L. J., Blumenthal, R. S., Jones, S. R. & Martin, S. S. Jul 1 2017 In : Journal of Clinical Lipidology. 11, 4, p. 1065-1072 8 p.

Research output: Research - peer-reviewArticle

LDL Lipoproteins
LDL Cholesterol
Nutrition Surveys
Apolipoproteins B
Hydroxymethylglutaryl-CoA Reductase Inhibitors

Family History of CHD Is Associated With Severe CAC in South Asians: Comparing the MASALA and MESA Studies

Patel, J., Al Rifai, M., Cainzos-Achirica, M., Kandula, N. R., Kanaya, A. M., Khera, A., Blumenthal, R. S., Nasir, K., Blaha, M. J. & Joshi, P. H. Aug 1 2017 In : JACC: Cardiovascular Imaging. 10, 8, p. 958-960 3 p.

Research output: Research - peer-reviewLetter

Higher Fitness Is Strongly Protective in Patients with Family History of Heart Disease: The FIT Project

Al Rifai, M., Patel, J., Hung, R. K., Nasir, K., Keteyian, S. J., Brawner, C. A., Ehrman, J. K., Sakr, S., Blumenthal, R. S., Blaha, M. J. & Al-Mallah, M. H. Mar 1 2017 In : American Journal of Medicine. 130, 3, p. 367-371 5 p.

Research output: Research - peer-reviewArticle

Heart Diseases
Exercise
Coronary Disease
Cardiorespiratory Fitness
Mortality

Impact of continuous positive airway pressure and oxygen on health status in patients with coronary heart disease, cardiovascular risk factors, and obstructive sleep apnea: A Heart Biomarker Evaluation in Apnea Treatment (HEARTBEAT) analysis

Lewis, E. F., Wang, R., Punjabi, N., Gottlieb, D. J., Quan, S. F., Bhatt, D. L., Patel, S. R., Mehra, R., Blumenthal, R. S., Weng, J., Rueschman, M. & Redline, S. Jul 1 2017 In : American Heart Journal. 189, p. 59-67 9 p.

Research output: Research - peer-reviewArticle

Continuous Positive Airway Pressure
Obstructive Sleep Apnea
Apnea
Health Status
Coronary Disease

Implications of Coronary Artery Calcium Testing for Treatment Decisions Among Statin Candidates According to the ACC/AHA Cholesterol Management Guidelines: A Cost-Effectiveness Analysis

Hong, J. C., Blankstein, R., Shaw, L. J., Padula, W. V., Arrieta, A., Fialkow, J. A., Blumenthal, R. S., Blaha, M. J., Krumholz, H. M. & Nasir, K. Aug 1 2017 In : JACC: Cardiovascular Imaging. 10, 8, p. 938-952 15 p.

Research output: Research - peer-reviewReview article

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cost-Benefit Analysis
Coronary Vessels
Cholesterol
Guidelines

National trends in statin use and expenditures in the US adult population from 2002 to 2013: Insights From the Medical Expenditure Panel Survey

Salami, J. A., Warraich, H., Valero-Elizondo, J., Spatz, E. S., Desai, N. R., Rana, J. S., Virani, S. S., Blankstein, R., Khera, A., Blaha, M. J., Blumenthal, R. S., Lloyd-Jones, D. & Nasir, K. Jan 1 2017 In : JAMA Cardiology. 2, 1, p. 56-65 10 p.

Research output: Research - peer-reviewArticle

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Health Expenditures
Population
Surveys and Questionnaires
Cardiovascular Diseases

Physical Activity, Obesity, and Subclinical Myocardial Damage

Florido, R., Ndumele, C. E., Kwak, L., Pang, Y., Matsushita, K., Schrack, J. A., Lazo, M., Nambi, V., Blumenthal, R. S., Folsom, A. R., Coresh, J., Ballantyne, C. M. & Selvin, E. May 1 2017 In : JACC: Heart Failure. 5, 5, p. 377-384 8 p.

Research output: Research - peer-reviewArticle

Obesity
Troponin T
Heart Failure
Odds Ratio
Confidence Intervals

Race/ethnic and sex disparities in the non-alcoholic fatty liver disease-abdominal aortic calcification association: The Multi-Ethnic Study of Atherosclerosis

Remigio-Baker, R. A., Allison, M. A., Forbang, N. I., Loomba, R., Anderson, C. A. M., Budoff, M., Schwimmer, J. B., Blumenthal, R. S., Ouyang, P. & Criqui, M. H. Mar 1 2017 In : Atherosclerosis. 258, p. 89-96 8 p.

Research output: Research - peer-reviewArticle

Atherosclerosis
Non-alcoholic Fatty Liver Disease
Sex Ratio
Linear Models
Spleen

Relation of Diastolic Blood Pressure and Coronary Artery Calcium to Coronary Events and Outcomes (From the Multi-Ethnic Study of Atherosclerosis)

Rahman, F., Al Rifai, M., Blaha, M. J., Nasir, K., Budoff, M. J., Psaty, B. M., Post, W. S., Blumenthal, R. S. & McEvoy, J. W. 2017 (Accepted/In press) In : American Journal of Cardiology.

Research output: Research - peer-reviewArticle

Atherosclerosis
Coronary Vessels
Blood Pressure
Calcium
Coronary Disease

Relation of Resting Heart Rate to Incident Atrial Fibrillation (from the Henry Ford Hospital Exercise Testing Project)

Aladin, A. I., Al Rifai, M., Rasool, S. H., Keteyian, S. J., Brawner, C. A., Blumenthal, R. S., Blaha, M. J., Al-Mallah, M. H. & McEvoy, J. W. Jan 15 2017 In : American Journal of Cardiology. 119, 2, p. 262-267 6 p.

Research output: Research - peer-reviewArticle

Atrial Fibrillation
Heart Rate
Exercise
Autonomic Nervous System
Exercise Test

Residual atherosclerotic cardiovascular disease risk in statin-treated adults: The Multi-Ethnic Study of Atherosclerosis

Wong, N. D., Zhao, Y., Quek, R. G. W., Blumenthal, R. S., Budoff, M. J., Cushman, M., Garg, P., Sandfort, V., Tsai, M. & Lopez, J. A. G. 2017 (Accepted/In press) In : Journal of Clinical Lipidology.

Research output: Research - peer-reviewArticle

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Atherosclerosis
Cardiovascular Diseases
Therapeutics
Tunica Intima

The 10-Year Prognostic Value of Zero and Minimal CAC

Joshi, P. H., Blaha, M. J., Budoff, M. J., Miedema, M. D., McClelland, R. L., Lima, J. A. C., Agatston, A. S., Blankstein, R., Blumenthal, R. S. & Nasir, K. Aug 1 2017 In : JACC: Cardiovascular Imaging. 10, 8, p. 957-958 2 p.

Research output: Research - peer-reviewLetter

The Identification of Calcified Coronary Plaque Is Associated With Initiation and Continuation of Pharmacological and Lifestyle Preventive Therapies: A Systematic Review and Meta-Analysis

Gupta, A., Lau, E., Varshney, R., Hulten, E. A., Cheezum, M., Bittencourt, M. S., Blaha, M. J., Wong, N. D., Blumenthal, R. S., Budoff, M. J., Umscheid, C. A., Nasir, K. & Blankstein, R. Aug 1 2017 In : JACC: Cardiovascular Imaging. 10, 8, p. 833-842 10 p.

Research output: Research - peer-reviewArticle

Meta-Analysis
Life Style
Odds Ratio
Pharmacology
Therapeutics

Thoracic aortic calcium, cardiovascular disease events, and all-cause mortality in asymptomatic individuals with zero coronary calcium: The Multi-Ethnic Study of Atherosclerosis (MESA)

Kim, J., Budoff, M. J., Nasir, K., Wong, N. D., Yeboah, J., Al-Mallah, M. H., Shea, S., Dardari, Z. A., Blumenthal, R. S., Blaha, M. J. & Cainzos-Achirica, M. Feb 1 2017 In : Atherosclerosis. 257, p. 1-8 8 p.

Research output: Research - peer-reviewArticle

Atherosclerosis
Cardiovascular Diseases
Thorax
Calcium
Mortality
Atherosclerosis
Thyroid Gland
Cardiovascular Diseases
Hypothyroidism
Stroke

Usefulness of Coronary Artery Calcium to Predict Heart Failure With Preserved Ejection Fraction in Men Versus Women (from the Multi-Ethnic Study of Atherosclerosis)

Sharma, K., Al Rifai, M., Ahmed, H. M., Dardari, Z., Silverman, M. G., Yeboah, J., Nasir, K., Sklo, M., Yancy, C., Russell, S. D., Blumenthal, R. S. & Blaha, M. J. 2017 (Accepted/In press) In : American Journal of Cardiology.

Research output: Research - peer-reviewArticle

Atherosclerosis
Coronary Vessels
Heart Failure
Calcium
Coronary Artery Disease

Use of sex-specific clinical and exercise risk scores to identify patients at increased risk for all-cause mortality

Cremer, P. C., Wu, Y., Ahmed, H. M., Pierson, L. M., Brennan, D. M., Al-Mallah, M. H., Brawner, C. A., Ehrman, J. K., Keteyian, S. J., Blumenthal, R. S., Blaha, M. J. & Cho, L. Jan 1 2017 In : JAMA Cardiology. 2, 1, p. 15-22 8 p.

Research output: Research - peer-reviewArticle

Exercise
Mortality
Nomograms
Calibration
Cohort Studies
2016

Age-dependent prognostic value of exercise capacity and derivation of fitne-aociated biologic age

Blaha, M. J., Hung, R. K., Dardari, Z., Feldman, D. I., Whelton, S. P., Nasir, K., Blumenthal, R. S., Brawner, C. A., Ehrman, J. K., Keteyian, S. J. & Al-Mallah, M. H. Mar 1 2016 In : Heart. 102, 6, p. 431-437 7 p.

Research output: Research - peer-reviewArticle

Exercise
Myocardial Infarction
Survival
Mortality
Proportional Hazards Models

All-cause mortality by age and gender based on coronary artery calcium scores

Nakanishi, R., Li, D., Blaha, M. J., Whelton, S. P., Darabian, S., Flores, F. R., Dailing, C., Blumenthal, R. S., Nasir, K., Berman, D. S. & Budoff, M. J. Nov 1 2016 In : European heart journal cardiovascular Imaging. 17, 11, p. 1305-1314 10 p.

Research output: Research - peer-reviewArticle

Coronary Vessels
Calcium
Mortality
Confidence Intervals
Population

An Update on the Utility of Coronary Artery Calcium Scoring for Coronary Heart Disease and Cardiovascular Disease Risk Prediction

Kianoush, S., Al Rifai, M., Cainzos-Achirica, M., Umapathi, P., Graham, G., Blumenthal, R. S., Nasir, K. & Blaha, M. J. Mar 1 2016 In : Current Atherosclerosis Reports. 18, 3, p. 13 1 p.

Research output: Research - peer-reviewReview article

Coronary Disease
Coronary Vessels
Cardiovascular Diseases
Calcium
Atherosclerotic Plaques

Association between life's simple 7 and noncardiovascular disease: The multi-ethnic study of atherosclerosis

Ogunmoroti, O., Allen, N. B., Cushman, M., Michos, E. D., Rundek, T., Rana, J. S., Blankstein, R., Blumenthal, R. S., Blaha, M. J., Veledar, E. & Nasir, K. 2016 In : Journal of the American Heart Association. 5, 10, e003954

Research output: Research - peer-reviewArticle

Atherosclerosis
Venous Thromboembolism
Pulmonary Embolism
Chronic Renal Insufficiency
Chronic Obstructive Pulmonary Disease

Association between non-alcoholic hepatic steatosis and hyper reactive blood pressure response on the exercise treadmill test

Laurinavicius, A. G., Bittencourt, M. S., Blaha, M. J., Nary, F. C., Kashiwagi, N. M., Conceiçao, R. D., Meneghelo, R. S., Prado, R. R., Carvalho, J. A. M., Nasir, K., Blumenthal, R. S. & Santos, R. D. Aug 1 2016 In : QJM. 109, 8, p. 531-537 7 p., hcw003

Research output: Research - peer-reviewArticle

Exercise Test
Blood Pressure
Liver
Hypertension
Ultrasonography

Association of variants in candidate genes with lipid profiles in women with early breast cancer on adjuvant aromatase inhibitor therapy

Santa-Maria, C. A., Blackford, A., Nguyen, A. T., Skaar, T. C., Philips, S., Oesterreich, S., Rae, J. M., Desta, Z., Robarge, J., Henry, N. L., Storniolo, A. M., Hayes, D. F., Blumenthal, R. S., Ouyang, P., Post, W. S., Flockhart, D. A. & Stearns, V. Mar 15 2016 In : Clinical Cancer Research. 22, 6, p. 1395-1402 8 p.

Research output: Research - peer-reviewArticle

Aromatase Inhibitors
Breast Neoplasms
Lipids
Genes
Therapeutics

Cardiovascular Disease Prevention in Men with Vascular Erectile Dysfunction: The View of the Preventive Cardiologist

Shah, N. P., Cainzos-Achirica, M., Feldman, D. I., Blumenthal, R. S., Nasir, K., Miner, M. M., Billups, K. L. & Blaha, M. J. Mar 1 2016 In : American Journal of Medicine. 129, 3, p. 251-259 9 p.

Research output: Research - peer-reviewArticle

Erectile Dysfunction
Blood Vessels
Cardiovascular Diseases
Cardiologists
Risk Management

Coronary artery Calcium predicts Cardiovascular events in participants with a low lifetime risk of Cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA)

Joshi, P. H., Patel, B., Blaha, M. J., Berry, J. D., Blankstein, R., Budoff, M. J., Wong, N., Agatston, A., Blumenthal, R. S. & Nasir, K. Mar 1 2016 In : Atherosclerosis. 246, p. 367-373 7 p.

Research output: Research - peer-reviewArticle

Atherosclerosis
Coronary Vessels
Cardiovascular Diseases
Calcium
Coronary Disease

Coronary Artery Calcium to Guide a Personalized Risk-Based Approach to Initiation and Intensification of Antihypertensive Therapy

McEvoy, J. W., Martin, S. S., Dardari, Z. A., Miedema, M. D., Sandfort, V., Yeboah, J., Budoff, M. J., Goff, D. C., Psaty, B. M., Post, W. S., Nasir, K., Blumenthal, R. S. & Blaha, M. J. Dec 9 2016 (Accepted/In press) In : Circulation.

Research output: Research - peer-reviewArticle

Antihypertensive Agents
Coronary Vessels
Blood Pressure
Calcium
Therapeutics

Determinants of minimal elevation in high-sensitivity cardiac troponin T in the general population

Rubin, J., Matsushita, K., Lazo, M., Ballantyne, C. M., Nambi, V., Hoogeveen, R., Sharrett, A. R., Blumenthal, R. S., Coresh, J. & Selvin, E. Jan 4 2016 (Accepted/In press) In : Clinical Biochemistry.

Research output: Research - peer-reviewArticle

Troponin T
Population
Cardiovascular Diseases
Hypertension
Health

Diastolic Blood Pressure, Subclinical Myocardial Damage, and Cardiac Events: Implications for Blood Pressure Control

McEvoy, J. W., Chen, Y., Rawlings, A., Hoogeveen, R. C., Ballantyne, C. M., Blumenthal, R. S., Coresh, J. & Selvin, E. Oct 18 2016 In : Journal of the American College of Cardiology. 68, 16, p. 1713-1722 10 p.

Research output: Research - peer-reviewArticle

Blood Pressure
Troponin T
Coronary Disease
Hypotension
Atherosclerosis

Effect of Beta-Blocker Therapy, Maximal Heart Rate, and Exercise Capacity During Stress Testing on Long-Term Survival (from The Henry Ford Exercise Testing Project)

Hung, R. K., Al-Mallah, M. H., Whelton, S. P., Michos, E. D., Blumenthal, R. S., Ehrman, J. K., Brawner, C. A., Keteyian, S. J. & Blaha, M. J. May 31 2016 (Accepted/In press) In : American Journal of Cardiology.

Research output: Research - peer-reviewArticle

Heart Rate
Exercise
Survival
Therapeutics
Mortality

Elevated gamma-glutamyl transferase is associated with subclinical inflammation independent of cardiometabolic risk factors in an asymptomatic population: A cross-sectional study

Ali, S. S., Oni, E. T., Blaha, M. J., Veledar, E., Feiz, H. R., Feldman, T., Agatston, A. S., Blumenthal, R. S., Conceicao, R. D., Carvalho, J. A. M., Santos, R. D. & Nasir, K. May 18 2016 In : Nutrition and Metabolism. 13, 1, 37

Research output: Research - peer-reviewArticle

Transferases
Cross-Sectional Studies
Inflammation
Population
C-Reactive Protein

Fasting or Nonfasting Lipid Measurements It Depends on the Question

Driver, S. L., Martin, S. S., Gluckman, T. J., Clary, J. M., Blumenthal, R. S. & Stone, N. J. Mar 15 2016 In : Journal of the American College of Cardiology. 67, 10, p. 1227-1234 8 p.

Research output: Research - peer-reviewArticle

Fasting
Lipids
Therapeutics
Cardiovascular Diseases
Hypertriglyceridemia

High Exercise Capacity Attenuates the Risk of Early Mortality After a First Myocardial Infarction: The Henry Ford Exercise Testing (FIT) Project

Shaya, G. E., Al-Mallah, M. H., Hung, R. K., Nasir, K., Blumenthal, R. S., Ehrman, J. K., Keteyian, S. J., Brawner, C. A., Qureshi, W. T. & Blaha, M. J. Feb 1 2016 In : Mayo Clinic Proceedings. 91, 2, p. 129-139 11 p.

Research output: Research - peer-reviewArticle

Myocardial Infarction
Exercise
Mortality
Metabolic Equivalent
Logistic Models
Atherosclerosis
Heart Failure
Biomarkers
Incidence
Therapeutics

Improving Cardiovascular Disease Risk Prediction with Albuminuria and Glomerular Filtration Rate

Whelton, S. P., Leucker, T. M. & Blumenthal, R. S. Feb 1 2016 In : American Journal of Kidney Diseases. 67, 2, p. 179-181 3 p.

Research output: Research - peer-reviewArticle

Interpretation of the evidence for the efficacy and safety of statin therapy

Collins, R. , Reith, C. , Emberson, J. , Armitage, J. , Baigent, C. , Blackwell, L. , Blumenthal, R. , Danesh, J. , Smith, G. D. , DeMets, D. , Evans, S. , Law, M. , MacMahon, S. , Martin, S. , Neal, B. , Poulter, N. , Preiss, D. , Ridker, P. , Roberts, I. , Rodgers, A. & 8 others Sandercock, P., Schulz, K., Sever, P., Simes, J., Smeeth, L., Wald, N., Yusuf, S. & Peto, R. Nov 19 2016 In : The Lancet. 388, 10059, p. 2532-2561 30 p.

Research output: Research - peer-reviewReview article

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Safety
Therapeutics
Blood Vessels
Stroke

Left ventricular area on non-contrast cardiac computed tomography as a predictor of incident heart failure – The Multi-Ethnic Study of Atherosclerosis

Bittencourt, M. S., Blankstein, R., Mao, S., Rivera, J. J., Bertoni, A. G., Shaw, L. J., Blumenthal, R. S., Budoff, M. J. & Nasir, K. Nov 1 2016 In : Journal of Cardiovascular Computed Tomography. 10, 6, p. 500-506 7 p.

Research output: Research - peer-reviewArticle

Atherosclerosis
Heart Failure
Tomography
Cardiovascular Diseases
Body Surface Area

Lipid Management Guidelines from the Departments of Veteran Affairs and Defense: A Critique

Bennet, C. S., Dahagam, C. R., Virani, S. S., Martin, S. S., Blumenthal, R. S., Michos, E. D. & McEvoy, J. W. 2016 (Accepted/In press) In : American Journal of Medicine.

Research output: Research - peer-reviewArticle

Veterans
Guidelines
Lipids
Cardiovascular Diseases
Therapeutics

Nonalcoholic Fatty Liver Disease and Incident Cardiac Events the Multi-Ethnic Study of Atherosclerosis

Zeb, I., Li, D., Budoff, M. J., Katz, R., Lloyd-Jones, D., Agatston, A., Blumenthal, R. S., Blaha, M. J., Blankstein, R., Carr, J. & Nasir, K. Apr 26 2016 In : Journal of the American College of Cardiology. 67, 16, p. 1965-1966 2 p.

Research output: Research - peer-reviewArticle

Brain Natriuretic Peptide
Atherosclerosis
Heart Failure
Obesity
Body Mass Index

PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: Alirocumab

Dahagam, C., Goud, A., Abdelqader, A., Hendrani, A., Feinstein, M. J., Qamar, A., Joshi, P. H., Swiger, K. J., Byrne, K., Quispe, R., Jones, S. R., Blumenthal, R. S. & Martin, S. S. Mar 1 2016 In : Future Cardiology. 12, 2, p. 149-157 9 p.

Research output: Research - peer-reviewArticle

LDL Cholesterol
alirocumab
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Monoclonal Antibodies
Outcome Assessment (Health Care)

PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: Evolocumab

Dahagam, C., Goud, A., Abdelqader, A., Hendrani, A., Feinstein, M. J., Qamar, A., Joshi, P. H., Swiger, K. J., Byrne, K., Quispe, R., Jones, S. R., Blumenthal, R. S. & Martin, S. S. Mar 1 2016 In : Future Cardiology. 12, 2, p. 139-148 10 p.

Research output: Research - peer-reviewArticle

Hydroxymethylglutaryl-CoA Reductase Inhibitors
LDL Cholesterol
AMG 145
Therapeutics
Hyperlipoproteinemia Type II

Prevalence and prognostic implications of coronary artery calcification in low-risk women: A meta-analysis

Kavousi, M. , Desai, C. S. , Ayers, C. , Blumenthal, R. S. , Budoff, M. J. , Mahabadi, A. A. , Ikram, M. A. , Van Der Lugt, A. , Hofman, A. , Erbel, R. , Khera, A. , Geisel, M. H. , Jöckel, K. H. , Lehmann, N. , Hoffmann, U. , O'Donnell, C. J. , Massaro, J. M. , Liu, K. , Möhlenkamp, S. , Ning, H. & 2 others Franco, O. H. & Greenland, P. Nov 22 2016 In : JAMA - Journal of the American Medical Association. 316, 20, p. 2126-2134 9 p.

Research output: Research - peer-reviewArticle

Meta-Analysis
Coronary Vessels
Calcium
Cardiovascular Diseases
Coronary Disease