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(Circulation. 2001;104:2679.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Coronary Artery Calcification in Older Adults to Age 99

Prevalence and Risk Factors

Anne B. Newman, MD, MPH; Barbara L. Naydeck, MPH; Kim Sutton-Tyrrell, RN, DrPH; Adam Feldman, MD, MPH; Daniel Edmundowicz, MD; Lewis H. Kuller, MD, DrPH

From the Division of Geriatric Medicine (A.B.N., B.L.N.) and the Department of Epidemiology (A.B.N., K.S-T., A.F., D.E., L.H.K.), University of Pittsburgh, Pittsburgh, Pa.

Correspondence to Anne B. Newman, MD, MPH, University of Pittsburgh School of Medicine, Division of Geriatric Medicine, 3520 Fifth Avenue, Suite 300, Pittsburgh, PA 15213. E-mail anewman{at}pitt.edu

	Abstract

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Background— Coronary artery calcification has been proposed as a noninvasive method to assess cardiovascular disease (CVD) risk. However, the prevalence and risk factors for coronary artery calcification in populations >65 years have not been well studied.

Methods and Results— Electron beam tomography was performed to assess coronary artery calcium (CAC) in 614 older adults aged, on average, 80 years (range, 67 to 99 years); 367 (60%) were women, and 143 (23%) were black. Calcium scores ranged from 0 to 5459. Median scores were 622 for men and 205 for women. Scores increased by age and were lower in blacks than in whites. Nine percent of subjects (n=57) had no CAC, and 31% (n=190) had a score lower than 100. A history of CVD was associated with calcium score. Age, male sex, white race, CVD, triglyceride level, pack-years of smoking, and asthma, emphysema, or bronchitis (chronic obstructive pulmonary disease) were independently associated with CAC score in the fourth quartile.

Conclusions— A wide range of CAC scores was observed, suggesting adaptation with aging. CAC may have potential to predict CVD in older adults, but this remains to be determined.

Key Words: calcium • coronary diseases • aging

	Introduction

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Electron beam computed tomography (EBT) can rapidly and noninvasively detect and quantify calcified atherosclerotic plaque in the coronary arteries.¹ A higher quantity of coronary artery calcium (CAC) is associated with the likelihood of obstructive lesions by angiography,¹ and it is also associated with an increased risk of future cardiovascular disease (CVD) in middle-aged, referred populations.²

The value of screening the elderly is in question because autopsy³ and clinical⁴ studies suggest that coronary artery atherosclerosis and calcification are almost universal in those with advanced old age. No study has yet defined the "typical" levels of CAC found in unreferred populations of older adults, whether a sex difference persists into old age, or whether CAC would predict a higher risk of CVD events or mortality in this age group. Risk factors measured late in life have rather poor discrimination for determining highest risk of CVD events in old age.^5,6 CAC has been proposed as a potential method to improve risk discrimination.¹ In fact, noninvasive measures of disease have been proposed to account for the effect of age in prediction models of CVD risk.⁷

We examined CAC in an elderly cohort. We hypothesized there would be a strong relationship between calcification and age and that CAC would be associated with CVD. This report describes the distribution of CAC in late life and associations with CVD and CVD risk factors.

	Methods

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Study Population
Participants from the Pittsburgh, Pennsylvania, field center of the Cardiovascular Health Study were recruited for EBT between May 1998 and June 2000.⁸ This study was established to determine the risk factors for CVD in older adults.^9,10 Of 727 participants contacted at the last examination in 1998 to 1999, 614 participants (84%) underwent EBT scanning. Of the 113 nonparticipants, 16% died before the scan, 45% were ill, 16% could not travel, and 23% refused. Nonparticipants were of similar age, sex, and race as participants. All participants gave informed consent for examination and follow-up. The protocol was approved by the Institutional Review Board at the University of Pittsburgh.

Coronary Artery Calcification
CAC was assessed using an Imatron C-150 EBT scanner and the Agatston scoring method,¹¹ as described previously.⁸

Demographic and Cardiovascular Risk Factors
Age was assessed at the time of the EBT scan, and cardiovascular risk factors were assessed between 1992 to 1993 in both the original and added minority cohorts. Hypertension was defined as a participant having an average seated systolic blood pressure >160 mm Hg or an average seated diastolic blood pressure >95 mm Hg or self-reported hypertension and use of antihypertensive medication. Blood was collected and analyzed at the 1992 to 1993 examination,¹² with exception of C-reactive protein, which was run on stored baseline samples in 1997.¹³ Diabetes was defined as use of insulin or oral hypoglycemics or if glucose level exceeded 126 mg/dL (7.0 mmol/L). Body mass index was expressed as kilograms per meters squared (kg/m²). Cigarette smoking was reported as ever versus never, because there were few current smokers, and smoking exposure was also assessed using pack-years. Blood pressures were measured according to a standard protocol. Chronic obstructive pulmonary disease was defined by self-report of asthma, bronchitis, or emphysema diagnosed by a physician.

Other CVD
Prevalent clinical CVD was ascertained at the time of the scan using baseline and adjudicated events data. Baseline self-report data were validated by medical records.¹⁴ Events occurring after baseline were ascertained by phone contact or at the clinic examination every 6 months, validated by medical record review, and adjudicated by committee.¹⁵ CVD included history of myocardial infarction or angina, coronary artery bypass surgery or percutaneous transluminal angioplasty, congestive heart failure, stroke or transient ischemic attack, carotid surgery, peripheral vascular bypass surgery, angioplasty, or reported intermittent claudication. Subclinical CVD was assessed at the 1992 to 1993 examination and defined as an ankle-arm index <0.90, internal carotid wall thickness or common carotid wall thickness >80 percentile of subjects in the Cardiovascular Health Study population, carotid stenosis >25%, major ECG abnormalities, or a positive Rose questionnaire for angina or intermittent claudication.¹⁶

Statistical Analysis
The calcium score was highly skewed and not transformed to normality by common transformations. Therefore, median calcium scores were compared across demographic groups, and the distribution of characteristics across the quartiled calcium score was examined. For categorical variables, the ² test for trend was used. For continuous variables, means and SD or medians were reported, and either ANOVA or a median test was used as appropriate to establish significance. Multiple logistic regression was used to determine which factors were independently associated with the highest quartile of calcium versus the lower 3 quartiles. Stepwise linear regression was also used to determine factors independently associated with higher calcium score (log transformed).

	Results

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Participants’ ages ranged from 67 to 99 years, with mean age of 80.4 years (Table 1). Men were similar in age and race distribution to the women, but a higher proportion had clinical CVD (P=0.021). CAC scores ranged from 0 to 5459, with a mean of 671 and median of 330 (622 for men and 205 for women; P<0.0001), and this broad distribution of scores was seen in both men and women (Figure 1). Fifty-seven participants (9.3%) had a score of 0 (6% of men compared with 11.4% of women; P=0.024). An additional 133 (21.7%) had a score <100, and 336 (54.7%) had a score <400. Fewer women than men had a score >1000 (13% of women compared with 34% of men; P<0.0001). The median score increased with age in both men and women but, in women, the score lagged about 10 years behind the men (Figure 2). For example, the score was 542 for women aged 85 to 99 years compared with 539 in men aged 75 to 79 years.

View this table: [in this window] [in a new window]   Table 1. Characteristics of the Study Population

View larger version (45K): [in this window] [in a new window]   Figure 1. Distribution of CAC scores in men (top) and women (bottom).

View larger version (42K): [in this window] [in a new window]   Figure 2. Median CAC scores in men and women by age group.

Those in the highest quartile of CAC score were older, more likely to be men, and less likely to be black (all P<0.0001; Table 2). In the lowest quartile of calcium, 9.7% were >85 years compared with 26.3% in the highest quartile. In the lowest quartile, 71.0% were women compared with only 40.1% in the highest quartile. Those in the higher quartiles were less likely to be black. All differences were significant with adjustment for age and sex.

View this table: [in this window] [in a new window]   Table 2. Demographics by Quartiles of CAC Score (n=614)

Higher calcium scores were associated with the prevalence of clinical CVD (for those with clinical CVD: median 683, range 0 to 5459; for those with subclinical CVD by other measures: median 374, range 0 to 4151; for those without atherosclerosis by other study measures: median 122, range 0 to 3736; P<0.0001). Forty percent of those with clinical CVD were in the highest calcium score quartile compared with 18.6% in the lowest quartile (Table 3). Conversely, of those without CVD by other measures, 13.2% were in the highest quartile and 37.1% were in the lowest quartile. This pattern was seen for both men and women, and associations remained significant after adjusting for age.

View this table: [in this window] [in a new window]   Table 3. Association Between Prevalence of CVD and Quartiles of CAC Score

The associations between CVD risk factors and the calcium score quartiles were then analyzed separately for men and women (Tables 4 and 5). In both men and women, age was associated with higher calcium levels. Although fewer blacks were among those with the highest levels of coronary calcium, the association between race and coronary calcium quartile was significant for men only. The prevalence of hypertension or diabetes was not significantly different across quartiles of calcium score. There was also no difference in the level of total, LDL, or HDL cholesterol across quartiles of CAC in either men or women. The median triglyceride level increased across the calcium quartiles for both men and women, although the relationship was borderline significant only in women (P=0.05). Smoking exposure, as measured by pack-years, was significantly different across CAC quartiles for both women (P=0.02) and men (P=0.01). Median C-reactive protein level was associated with a higher level of CAC in women (P=0.003). In men, C-reactive protein levels tended to be lower overall and seemed to be unrelated to the calcium score. Overall, those at the extremes of the distribution (lowest versus highest quartile) had more pronounced differences in the risk factors in the expected direction. Rank correlations between risk factors and the calcium score quartile were low (<0.20) and not significant except for age, race, sex, and pack-years of smoking. Results were similar when those with clinical CVD were excluded.

View this table: [in this window] [in a new window]   Table 4. Prevalence and Means/Medians of Baseline Risk Factors by Level of CAC in Men

View this table: [in this window] [in a new window]   Table 5. Prevalence and Means/Medians of Baseline Risk Factors by Level of CAC in Women

Finally, we evaluated risk factors predicting a CAC score in the fourth quartile (Table 6). Men with clinical CVD who were older or of white race were more likely to be in the top quartile. In addition, triglycerides, smoking exposure, and history of chronic obstructive pulmonary disease were independently associated with the highest quartile. Results were similar when using the log of the calcium score as the dependent variable.

View this table: [in this window] [in a new window]   Table 6. Multiple Logistic Regression: Factors Independently Associated With Highest Quartile of Calcium Score

	Discussion

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The key findings of this study were that the extent of coronary artery calcification was strongly associated with age through the ninth decade in men and women and was associated with CVD. Second, risk factor levels were only weakly associated with the extent of CAC in these older adults.

There is reason to believe that older adults might differ from younger adults in the rate of progression of atherosclerosis, the level of compensatory dilation or stiffening, and/or in plaque stability. Intracoronary ultrasound illustrates that there is compensatory dilation of the coronary artery at the site of obstruction.¹⁷ Our study suggests that such compensation may well occur with aging based on the fact that those >85 years in our study had median levels of coronary calcium well over the threshold for significant obstructive disease,¹ yet 57% had not had a cardiovascular event. These high levels of calcification are unusual in middle-aged and younger adults. Although CAC represents the extent of atherosclerosis, a given level of calcium may have different a predictive value in the old than in the young. This hypothesis must be tested prospectively.

The utility of CAC assessment in older adults has been questioned because most clinical series show that calcification is nearly universal⁴ and not discriminatory. Our data refute this in that the range of calcification was quite broad, spanning the lowest to the highest levels. Furthermore, the extent of calcification was associated with the extent of CVD (clinical or subclinical by other measures) in our study. Therefore, it seems likely that it may also discriminate risk prospectively in this older cohort.

These data extend findings in middle-aged adults in that there is a very strong effect of age on CAC scores. Calcification is first detected in most men at around age 40, whereas women first show calcification around age 50.¹⁸ Raggi et al¹⁹ reported median calcium levels of zero in middle-aged women and median scores of 151 in men and 24 in women aged 65 to 70 years. In our group, the medians for men and women up to age 75 were 167 and 126, with substantially higher scores in each subsequent 5-year age group. Although women had lower levels of calcification than men, levels in the oldest age group were similar to those of men 10 years younger.

Blacks were less likely to have extensive coronary artery calcification in this cohort than were whites. The literature on differences in CAC by race is just beginning to emerge, with one study showing similar rates of calcification in blacks and whites²⁰ and one showing lower rates in blacks.²¹ It is possible that the blacks recruited into this study are not representative of those in these other studies or in the community or, because of their age, are a unique survival group. Because they were recruited later, the blacks were somewhat younger than the whites; however, this association persisted with adjustment for age. More detailed analyses of these differences in our cohort are underway.

The finding of weak associations between the extent of coronary calcification and baseline risk factors, including hypertension, diabetes, and cholesterol, was consistent with other studies showing that such risk factors are attenuated in their associations with disease in old age.^22–24 We examined risk factors assessed 5 years before the scan. Risk factor levels in older adults decline in those who become ill and in those whose risk factors are treated, so these prior risk factor levels should better reflect risk factor exposure than current levels in older adults.^25,26 Furthermore, all studies of elderly individuals are subject to survivor bias, which results in truncation of the distributions of risk factors and disease. For example, in our study, men had low levels of C-reactive protein at all levels of calcification, supporting a survival bias in the men. Also, these surviving individuals represent less than half of the original 1501 members of the Cardiovascular Health Study cohort in Pittsburgh. However, these individuals would be similar to older adults seen in a community. Nevertheless, such bias is an important limitation to consider.

Because so many older adults are at risk, further study of risk discrimination is needed.⁷ On the basis of current recommendations, high scores such as those noted in these older adults could potentially stimulate further evaluation for invasive therapy, despite a lack of evidence for intervening in asymptomatic people. In this study, 59% of men and 36% of women had scores >400, which is the current guideline for referral for evaluation for obstructive disease.¹³ This approach would be unrealistic given the large number of older adults who would have high scores.

In summary, CAC scanning detected a broad range of disease in these older adults, and many with higher levels of calcification would not have been distinguished by traditional risk factors. The higher levels of CAC in those with clinical disease suggest that it should predict events prospectively. Although higher CAC has been shown to predict events in middle-aged, clinically-referred populations, it remains to be determined whether the risk associated with CAC is attenuated with age.

	Appendix

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Participating Institutions and Principal Staff of the Cardiovascular Health Study
Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC: Gregory L. Burke, Sharon Jackson, Alan Elster, Curt D. Furberg, Gerardo Heiss, Dalane Kitzman, Margie Lamb, David S. Lefkowitz, Mary F. Lyles, Cathy Nunn, Ward Riley, John Chen, and Beverly Tucker; ECG Reading Center, Wake Forest University, Winston-Salem, NC: Farida Rautaharju and Pentti Rautaharju; University of California, Davis: William Bonekat, Charles Bernick, Michael Buonocore, Mary Haan, Calvin Hirsch, Lawrence Laslett, Marshall Lee, John Robbins, William Seavey, and Richard White; The Johns Hopkins University, Baltimore, Md: M. Jan Busby-Whitehead, Joyce Chabot, George W. Comstock, Adrian Dobs, Linda P. Fried, Joel G. Hill, Steven J. Kittner, Shiriki Kumanyika, David Levine, Joao A. Lima, Neil R. Powe, Thomas R. Price, Jeff Williamson, Moyses Szklo, and Melvyn Tockman; MRI Reading Center, The Johns Hopkins University, Baltimore, Md: Norman Beauchamp, R. Nick Bryan, Douglas Fellows, Melanie Hawkins, Patrice Holtz, Naiyer Iman, Michael Kraut, Cynthia Quinn, Grace Lee, Carolyn C. Meltzer, Larry Schertz, Earl P. Steinberg, Scott Wells, Linda Wilkins, and Nancy C. Yue; University of Pittsburgh, Pittsburgh, Pa: Diane G. Ives, Charles A. Jungreis, Laurie Knepper, Lewis H. Kuller, Elaine Meilahn, Peg Meyer, Roberta Moyer, Anne Newman, Richard Schulz, Vivienne E. Smith, and Sidney K. Wolfson; Echocardiography Reading Center (Baseline), University of California, Irvine: Hoda Anton-Culver, Julius M. Gardin, Margaret Knoll, Tom Kurosaki, and Nathan Wong; Echocardiography Reading Center (Follow-Up), Georgetown Medical Center, Washington, DC: John Gottdiener, Eva Hausner, Stephen Kraus, Judy Gay, Sue Livengood, Mary Ann Yohe, and Retha Webb; Ultrasound Reading Center, New England Medical Center, Boston, Mass: Daniel H. O’Leary, Joseph F. Polak, and Laurie Funk; Central Blood Analysis Laboratory, University of Vermont, Burlington: Elaine Cornell, Mary Cushman, and Russell P. Tracy; Pulmonary Reading Center, University of Arizona, Tucson: Paul Enright; Coordinating Center, University of Washington, Seattle: Alice Arnold, Annette L. Fitzpatrick, Richard A. Kronmal, Bruce M. Psaty, David S. Siscovick, Will Longstreth, Patricia W. Wahl, David Yanez, Paula Diehr, Corrine Dulberg, Bonnie Lind, Thomas Lumley, Ellen O’Meara, Jennifer Nelson, and Charles Spiekerman; National Heart, Lung, and Blood Institute Project Office, Bethesda, Md: Diane Bild, Teri A. Manolio, Peter J. Savage, and Patricia Smith.

	Acknowledgments

 
Supported by National Heart, Lung, and Blood Institute grant R01-HL-64587 and National Heart, Lung, and Blood Institute contracts N01-HC-85079 through 85086.

	Footnotes

 
A complete list of investigators of the Cardiovascular Heath Study can be found in the Appendix.

Received August 23, 2001; revision received September 18, 2001; accepted September 19, 2001.

	References

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1. O’Rourke RA, Brundage BH, Froelicher VF, et al. American College of Cardiology/American Heart Association expert consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. J Am Coll Cardiol.. 2000; 36: 326–340.[Free Full Text]

2. Arad Y, Spadaro LA, Goodman K, et al. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol.. 2000; 36: 1253–1260.[Abstract/Free Full Text]

3. Sangiorgi G, Rumberger JA, Severson A, et al. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol.. 1998; 31: 126–33.[Abstract/Free Full Text]

4. Janowitz WR, Agatston AS, Kaplan G, et al. Differences in prevalence and extent of coronary artery calcium detected by ultrafast computed tomography in asymptomatic men and women. Am J Cardiol.. 1993; 72: 247–254.[Medline] [Order article via Infotrieve]

5. Grundy SM, Cleeman JI, Rifkind BM, et al, for the Coordinating Committee of the National Cholesterol Education Program. Cholesterol lowering in the elderly population. Arch Intern Med.. 1999; 159: 1670–1678.[Abstract/Free Full Text]

6. Avins AL, Browner WS. Improving the prediction of coronary heart disease to aid in the management of high cholesterol levels: what a difference a decade makes. JAMA.. 1998; 279: 445–449.[Abstract/Free Full Text]

7. Grundy SM. Age as a risk factor: you are as old as your arteries. Am J Cardiol.. 1999; 83: 1455–1457.[Medline] [Order article via Infotrieve]

8. Newman AB, Naydeck B, Sutton-Tyrrell K, et al. Coronary artery calcification in older adults with minimal clinical or subclinical cardiovascular disease. J Am Geriatr Soc.. 2000; 48: 256–263.[Medline] [Order article via Infotrieve]

9. Fried LP, Borhani NO, Enright P, et al, for the Cardiovascular Health Study Research Group (CHS). The Cardiovascular Health Study: design and rationale. Ann Epidemiol.. 1991; 1: 263–276.[Medline] [Order article via Infotrieve]

10. Tell GS, Fried LP, Hermanson B, et al, for the Cardiovascular Health Study (CHS) Collaborative Research Group. Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. Ann Epidemiol.. 1993; 3: 358–366.[Medline] [Order article via Infotrieve]

11. Agatston AS, Janowitz WR, Kaplan G, et al. Ultrafast computed tomography-detected coronary calcium reflects the angiographic extent of coronary arterial atherosclerosis. Am J Cardiol.. 1994; 74: 1272–1274.[Medline] [Order article via Infotrieve]

12. Cushman M, Cornell E, Howard P, et al. Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem.. 1995; 41: 264–270.[Abstract/Free Full Text]

13. Macy EM, Hayes TE, Tracy RP. Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications. Clin Chem.. 1997; 43: 52–58.[Abstract/Free Full Text]

14. Mittelmark MG, Psaty BM, Rautaharju PM, et al. Prevalence of cardiovascular diseases among older adults: the Cardiovascular Health Study. Am J Epidemiol.. 1993; 137: 311–317.[Abstract/Free Full Text]

15. Ives DG, Fitzpatrick AL, Bild DE, et al. Surveillance and ascertainment of cardiovascular events: the Cardiovascular Health Study. Ann Epidemiol.. 1995; 5: 278–285.[Medline] [Order article via Infotrieve]

16. Kuller LH, Fisher L, McClelland R, et al. Differences in prevalence and risk factors for subclinical vascular disease among black and white participants in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol.. 1998; 18: 283–293.[Abstract/Free Full Text]

17. Baumgart D, Schmermund A, Guenter G, et al. Comparison of electron beam computed tomography with intracoronary ultrasound and coronary angiography for detection of coronary atherosclerosis. J Am Coll Cardiol.. 1997; 30: 57–64.[Abstract]

18. Tejada C, Strong JP, Montenegro MR, et al. Distribution of coronary and aortic atherosclerosis by geographic location, race and sex. Lab Invest.. 1968; 18: 509–526.[Medline] [Order article via Infotrieve]

19. Raggi P, Callister TQ, Cooil B, et al. Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography. Circulation.. 2000; 101: 850–855.[Abstract/Free Full Text]

20. Iribarren C, Sidney S, Bild DE, et al. Association of hostility with coronary artery calcification in young adults: the CARDIA Study. JAMA.. 2000; 283: 2546–2551.[Abstract/Free Full Text]

21. Doherty TM, Tank W, Detrano RC. Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factors. J Am Coll Cardiol.. 1999; 34: 787–794.[Abstract/Free Full Text]

22. Newman AB, Shemanski L, Manolio TA, et al, for the Cardiovascular Health Study Collaborative Research Group. Ankle-arm index as a predictor of cardiovascular disease and mortality in the cardiovascular health study. Arterioscler Thromb Vasc Biol.. 1999; 19: 538–545.[Abstract/Free Full Text]

23. Stamler J, Wentworth D, Neaton JD, for the MRFIT Research Group. Is the relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? JAMA. 1986; 256: 2823–2828.[Abstract/Free Full Text]

24. Frost PH, Davis BR, Burlando AJ. Coronary heart disease risk factors in men and women aged 65 and older (SHEP). Circulation.. 1996; 94: 26–34.[Abstract/Free Full Text]

25. Benfante R, Hwang LJ, Masaki K, et al. To what extent do cardiovascular risk factor values measured in elderly men represent their midlife values measured 25 years earlier? A preliminary report and commentary from the Honolulu Heart Program. Am J Epidemiol.. 1994; 140: 206–216.[Abstract/Free Full Text]

26. Corti MC, Guralnik JM, Salive ME, et al. Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons. Ann Intern Med.. 1997; 26: 753–760.

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				T. M. Doherty, L. A. Fitzpatrick, A. Shaheen, T. B. Rajavashisth, and R. C. Detrano Genetic Determinants of Arterial Calcification Associated With Atherosclerosis Mayo Clin. Proc., February 1, 2004; 79(2): 197 - 210. [Abstract] [PDF]

				T. Weber, J. Auer, M. F. O'Rourke, E. Kvas, E. Lassnig, R. Berent, and B. Eber Arterial Stiffness, Wave Reflections, and the Risk of Coronary Artery Disease Circulation, January 20, 2004; 109(2): 184 - 189. [Abstract] [Full Text] [PDF]

				J. Zhu, R. J. Katz, A. A. Quyyumi, D. A. Canos, D. Rott, G. Csako, A. Zalles-Ganley, J. Ogunmakinwa, A. G. Wasserman, and S. E. Epstein Association of Serum Antibodies to Heat-Shock Protein 65 With Coronary Calcification Levels: Suggestion of Pathogen-Triggered Autoimmunity in Early Atherosclerosis Circulation, January 6, 2004; 109(1): 36 - 41. [Abstract] [Full Text] [PDF]

				H.-H. S. Oei, R. Vliegenthart, A. Hofman, M. Oudkerk, and J. C.M. Witteman Risk factors for coronary calcification in older subjects: The Rotterdam Coronary Calcification Study Eur. Heart J., January 1, 2004; 25(1): 48 - 55. [Abstract] [Full Text] [PDF]

				M. P. Reilly, M. L. Wolfe, A. R. Localio, and D. J. Rader C-Reactive Protein and Coronary Artery Calcification: The Study of Inherited Risk of Coronary Atherosclerosis (SIRCA) Arterioscler Thromb Vasc Biol, October 1, 2003; 23(10): 1851 - 1856. [Abstract] [Full Text] [PDF]

				A. B. Newman Commentary J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2003; 58(7): M666 - 667. [Full Text] [PDF]

				D. B. Mark, L. J. Shaw, M. S. Lauer, P. G. O'Malley, and P. Heidenreich Task force #5--is atherosclerosis imaging cost effective? J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1906 - 1917. [Full Text] [PDF]

				C. S. Fox, R. S. Vasan, H. Parise, D. Levy, C. J. O'Donnell, R. B. D'Agostino, and E. J. Benjamin Mitral Annular Calcification Predicts Cardiovascular Morbidity and Mortality: The Framingham Heart Study Circulation, March 25, 2003; 107(11): 1492 - 1496. [Abstract] [Full Text] [PDF]

				T. C. Lee, P. G. O'Malley, I. Feuerstein, and A. J. Taylor The prevalence and severity of coronaryartery calcification on coronary arterycomputed tomography in black and white subjects J. Am. Coll. Cardiol., January 1, 2003; 41(1): 39 - 44. [Abstract] [Full Text] [PDF]

				R. Detrano The ethnic-specific natureof mechanisms forcoronary heart disease J. Am. Coll. Cardiol., January 1, 2003; 41(1): 45 - 46. [Full Text] [PDF]

				G. J. Blake and P. M. Ridker C-Reactive Protein, Subclinical Atherosclerosis, and Risk of Cardiovascular Events Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1512 - 1513. [Full Text] [PDF]

				H. M. Colhoun, C. Schalkwijk, M. B. Rubens, and C. D.A. Stehouwer C-Reactive Protein in Type 1 Diabetes and Its Relationship to Coronary Artery Calcification Diabetes Care, October 1, 2002; 25(10): 1813 - 1817. [Abstract] [Full Text] [PDF]

				K. Ikeda, H. Ohno, M. Tamura, H. Kashihara, K. Anan, K.-i. Hosozawa, M. Kinoshita, Y. Iwasaki, R. Vliegenthart, and J. C.M. Witteman Cerebral Atherosclerosis and Coronary Calcification Stroke, October 1, 2002; 33(10): 2345 - 2346. [Full Text] [PDF]

				T. J. Wang, B.-H. Nam, P. W.F. Wilson, P. A. Wolf, D. Levy, J. F. Polak, R. B. D'Agostino, and C. J. O'Donnell Association of C-Reactive Protein With Carotid Atherosclerosis in Men and Women: The Framingham Heart Study Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1662 - 1667. [Abstract] [Full Text] [PDF]

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				T. J. Wang, M. G. Larson, D. Levy, E. J. Benjamin, M. J. Kupka, W. J. Manning, M. E. Clouse, R. B. D'Agostino, P. W.F. Wilson, and C. J. O'Donnell C-Reactive Protein Is Associated With Subclinical Epicardial Coronary Calcification in Men and Women: The Framingham Heart Study Circulation, September 3, 2002; 106(10): 1189 - 1191. [Abstract] [Full Text] [PDF]

				L. L Demer Vascular calcification and osteoporosis: inflammatory responses to oxidized lipids Int. J. Epidemiol., August 1, 2002; 31(4): 737 - 741. [Full Text] [PDF]

				L. Kuller, A. Arnold, R. Tracy, J. Otvos, G. Burke, B. Psaty, D. Siscovick, D. S. Freedman, and R. Kronmal Nuclear Magnetic Resonance Spectroscopy of Lipoproteins and Risk of Coronary Heart Disease in the Cardiovascular Health Study Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1175 - 1180. [Abstract] [Full Text] [PDF]

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