This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Doherty, T. M. Articles by Detrano, R. C. Search for Related Content PubMed PubMed Citation Articles by Doherty, T. M. Articles by Detrano, R. C.

(Circulation. 1997;96:1477-1481.)
© 1997 American Heart Association, Inc.

Articles

Ethnic Origin and Serum Levels of 1,25-Dihydroxyvitamin D₃ Are Independent Predictors of Coronary Calcium Mass Measured by Electron-Beam Computed Tomography

Terence M. Doherty, BA; Weiyi Tang, MD; Steven Dascalos, BA; Karol E. Watson, MD; Linda L. Demer, MD, PhD; Robert M. Shavelle, PhD; ; Robert C. Detrano, MD, PhD

From the Division of Cardiology, Department of Medicine, Harbor–UCLA Medical Center, and the Saint John's Cardiovascular Research Center (T.M.D., W.T., S.D., R.C.D.), Torrance, Calif; Division of Cardiology (K.E.W., L.L.D.), Department of Medicine, UCLA School of Medicine, Los Angeles, Calif; and Department of Statistics (R.M.S.), University of California, Riverside.

Correspondence to Robert Detrano, MD, PhD, Division of Cardiology, Harbor–UCLA Medical Center, 1124 W Carson St, RB-2, Torrance, CA 90502. E-mail detrano{at}harbor4.humc.edu

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background Blacks have been found to have lower amounts of coronary calcium as well as higher levels of the osteoregulatory steroid 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] than whites. We sought to determine if racial differences in coronary calcium mass could be explained by differences in serum levels of 1,25(OH)₂D₃.

Methods and Results We evaluated standard coronary risk factors, quantified coronary calcium mass with electron-beam computed tomography (EBCT), and measured serum 1,25(OH)₂D₃ with radioimmunoassay in 283 high-risk subjects (51 [18%] black, 232 [82%] white). Black subjects had lower masses of coronary calcium than whites (14 versus 47 mg; P=.003). Serum 1,25(OH)₂D₃ levels were slightly higher in blacks (41 versus 38 pg/mL; P=.05). Log 1,25(OH)₂D₃ levels were inversely proportional to log-transformed calcium mass (r=-.19; P=.001) in both races. Multivariate linear regression demonstrated that both black race (P=.02) and 1,25(OH)₂D₃ levels (P=.007) contributed inversely and independently to coronary calcium mass. However, an interaction term of racex1,25(OH)₂D₃ did not significantly contribute to coronary calcium mass, indicating that other undetermined factors in addition to 1,25(OH)₂D₃ are responsible for ethnic differences in coronary calcium mass.

Conclusions Both black race and serum levels of 1,25(OH)₂D₃ are independent negative determinants of coronary calcium mass. Nevertheless, diminished amounts of coronary calcium in blacks are not accounted for by higher 1,25(OH)₂D₃ levels.

Key Words: calcium • vitamin D • race • tomography

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
On the basis of pathological findings that the presence of coronary arterial calcification indicates concomitant atherosclerotic disease,^{1 2} noninvasive radiographic evaluation has been proposed as a screening tool for the detection of coronary artery disease. However, although the amount of calcification correlates moderately well with the severity of obstructive coronary disease compared with angiography or histopathology,^{3 4} the presence of calcification as well as its sensitivity and specificity in identifying obstructive disease may be influenced by factors such as age^{5 6 7 8 9} and sex.^{6 8 9 10} We have shown that asymptomatic but high-risk black subjects have a significantly lower incidence of coronary calcification than whites despite having a similar risk factor profile¹¹ and higher subsequent numbers of coronary events¹² and thus, presumably, a similar extent of coronary atherosclerotic disease. Might the pathobiological determinants of calcification, then, be different in blacks compared with whites?

Current theory conceptualizes atherosclerotic calcification as an active, regulated process similar to osteogenesis,^{13 14 15} yet the details and possible ethnic differences in this regulation remain unknown. The steroid hormone 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], the active metabolite of vitamin D, performs a fundamental role in the biology of mineralized tissues and in the maintenance of calcium homeostasis.^{16 17} Like other steroid hormones, 1,25(OH)₂D₃ exerts its biological effects by binding to intracellular receptors, which results in either stimulation or repression of gene transcription. In bone, the effects of 1,25(OH)₂D₃ are complex and incompletely understood, but 1,25(OH)₂D₃ plays an important role in both the initiation of new bone formation and the stimulation of bone resorption.^{16 18}

In addition to having less coronary calcification,¹¹ blacks have greater bone mass^{19 20 21} and a lower incidence of osteoporosis and hip fractures^{22 23 24} than whites, despite a lower calcium intake²⁵ and a diminished rate of new bone formation.²⁶ These ethnic differences in bone metabolism have been attributed to differences in the vitamin D–endocrine system.^{27 28} Blacks have been shown to have higher serum levels of 1,25(OH)₂D₃ and lower serum levels of 25-hydroxyvitamin D₃ than whites,^{28 29 30 31 32} a result of diminished cutaneous synthesis in black pigmented skin of the precursor to 25-hydroxyvitamin D₃, cholecalciferol, a process that depends on ultraviolet photochemical conversion.^{28 29 32} These considerations led us to investigate the possible role of vitamin D metabolism in the development of coronary arterial calcification in both black and white asymptomatic but high-risk subjects.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Study Sample
The South Bay Heart Watch cohort consisted of 1461 adult subjects at high risk for coronary heart disease who underwent digital subtraction fluoroscopy^{8 33} and standard coronary risk factor determination³⁴ between January 1990 and December 1992. To qualify for enrollment, all subjects were required to have a 5% probability of suffering a coronary heart disease event within 4 years as calculated by use of the Framingham algorithm.³⁴ Two years after initial enrollment, risk factor evaluation, and fluoroscopic assessment of coronary calcification, 1304 of these subjects underwent electron-beam computed tomographic (EBCT) scanning (to quantify coronary calcium mass) and repeat risk factor determination. All risk factor data in this report are derived from the risk factor assessment performed at the time of the EBCT exam. Three hundred thirty-eight subjects, including all of the black subjects (n=51) as well as a random subsample of the white subjects (n=287), underwent fasting phlebotomy for quantification of serum lipoproteins and 1,25(OH)₂D₃. Subjects with hyperparathyroidism, chronic renal failure (serum creatinine >2), or known malignancy were excluded, leaving 283 subjects (51 [18%] black, 232 [82%] white) who were free of these conditions.

EBCT Scans
EBCT studies were obtained by use of an Imatron C-100 computed tomographic scanner, without contrast and with the patient supine. Breath was held at end expiration, exposure time was 100 ms per image slice, and total skin radiation was <6 Gy/scan. Image acquisition was triggered electrocardiographically at the same point in the cardiac cycle during diastole (80% of the RR interval). Transverse image slices of the heart were obtained contiguously beginning 1 cm below the carina and progressing caudally. Before the initiation of this investigation, the EBCT scanner was examined by a radiation physicist and was found to function without interslice gaps or overlaps. A standard calibration phantom^{35 36} was scanned with each subject, allowing calculation of calibrated mass estimates of hydroxyapatite content in each coronary artery and standardized estimation of image noise in each slice. All EBCT scans used a 6-mm image-slice protocol.³⁷

Each scan was examined by a cardiologist experienced in both coronary angiography and EBCT imaging. The area of each pixel was 0.34 mm². A region of interest 66 mm² in area^{35 36} was created that was centered on each focus of coronary calcification, defined as a volume of 8.2 mm³ (four contiguous pixels with a CT number >130 Hounsfield units [HU]³⁸ within the distribution of a coronary artery). The mean and peak CT numbers and the area of the subsets of pixels with a CT number >0 HU within these regions were calculated. The estimated mass of calcium phosphate was calculated for each artery by use of a previously published arterial summation.^{35 36 37}

Demographic Factors
Before EBCT scanning, subjects were interviewed and standard coronary risk factor data were obtained. All risk factor results in this report are based on this assessment rather than that performed 2 years earlier when subjects were initially enrolled in the South Bay Heart Watch study. Ethnicity was determined by asking subjects whether they considered themselves to be black, Asian-American, Native-American, or white. In a separate question, subjects were asked if they considered themselves to be of Hispanic origin or otherwise. Therefore, both Hispanics and non-Hispanics were divided among the four major racial categories listed above. Asian-American and Native-American subjects were excluded.

Risk Factor Evaluation
Evaluations were performed twice, at the time of recruitment and 2 years later within 1 week before EBCT scanning. All risk factor results in the present report are based on the latter assessment.

Family history of coronary heart disease was considered pertinent if a first-degree relative had suffered a myocardial infarction⁸ or had died suddenly before the age of 65 years. Smoking history was assessed by asking each subject if they had ever smoked >10 cigarettes/d for at least 1 year. Diabetes or hypertension was considered present if a subject was receiving dietary or medical therapy or both for these disorders.

Systolic and diastolic blood pressures were measured with a sphygmomanometer in duplicate at 3-minute intervals after the subject was allowed to rest in a sitting position for 5 minutes. Systolic and diastolic measurements differed by 3.4±7.8 and 0.4±0.5 mm Hg, respectively.

Blood samples were drawn after a 12-hour fast from an arm vein with subjects in a sitting position and allowed to coagulate at room temperature. The cholesterol oxidase technique was used to measure total cholesterol levels.

Analysis of 1,25(OH)₂D₃ Levels
Whole blood was collected by venipuncture in the fasting state. The serum was separated by centrifugation and stored at -80°C. Frozen serum samples were transferred to the host site for analysis. Serum concentration of 1,25(OH)₂D₃ was determined by radioimmunoassay (reagents from Nichols Institute). All samples were assayed in duplicate. Any pair that differed by >20% was reassayed. If sufficient serum was not available, the subject was excluded from analysis.

Statistical Analysis
Both 1,25(OH)₂D₃ levels and coronary calcium quantities were found to be distributed nonnormally (signed rank test, P<.001). Therefore, transformations of the form (log₁₀[x+1]) were applied to calcium mass and log₁₀X to 1,25(OH)₂D₃. Pearson correlation was used for all correlation coefficients. Wilcoxon nonparametric tests were used to compare 1,25(OH)₂D₃ levels and coronary calcium masses between groups. Multivariate linear regression was applied to determine predictors of calcium phosphate mass.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Demographic and Risk Factor Data
The mean age (±SD) of the subjects was 65±8 years (18% of subjects were black and 82% were white). Table 1 shows the results of risk factor assessment for both black and white subjects performed at the time of EBCT scanning. Blacks were significantly younger than their white counterparts (63±8 versus 66±8 years; P=.01), but no other significant differences were noted for the remaining risk factors of male sex, serum cholesterol, systolic blood pressure, history of diabetes, and history of smoking. The mean calculated Framingham risk³⁴ of a coronary heart disease event was similar in both racial groups (Table 1). Of the 283 subjects, 67 (24%) were taking cholesterol-lowering agents, 90 (32%) were taking aspirin, 31 (11%) were receiving ß-blockade therapy, 151 (53%) were taking other antihypertensive agents, and 92 (32%) were taking vitamin supplements, which might have included vitamin D. There were no significant differences between black and white subjects in consumption of any of these (data not shown).

View this table: [in this window] [in a new window]   Table 1. Coronary Heart Disease Risk Factors and Ethnicity

Correlations
Table 2 shows the Pearson correlation coefficients for log-transformed calcium phosphate mass, log 1,25(OH)₂D₃, and age. Table 3 shows coronary calcium phosphate mass, serum 1,25(OH)₂D₃ levels, and race. Watson et al³⁹ described an inverse and significant correlation (-.18) between log 1,25(OH)₂D₃ and log-transformed calcium phosphate mass. As noted by other investigators,^{7 33 40} there is a strong direct correlation between log-transformed calcium and age.

View this table: [in this window] [in a new window]   Table 2. Pearson Correlation Coefficients

View this table: [in this window] [in a new window]   Table 3. Coronary Calcium Phosphate Mass, Serum 1,25(OH)2D3, and Race

Multivariate Regression
Table 4 shows multivariate linear regression using log-transformed calcium phosphate mass as the dependent variable. Age, risk factors, log 1,25(OH)₂D₃, and race were used as independent candidate variables. This analysis demonstrated that age, race, diabetic history, and log 1,25(OH)₂D₃ were all significantly related to the mass of coronary calcium found in the arteries of the 283 subjects. Both black ethnicity and 1,25(OH)₂D₃ were inversely related to calcium phosphate mass, whereas age and diabetic history were directly related. When this calculation was repeated including an interaction term of racex1,25(OH)₂D₃, this interaction was not statistically significant. This implies that the effect of 1,25(OH)₂D₃ on coronary calcium mass is the same for the two races, as depicted graphically by the similar slopes of the regression lines in the Figure. Thus, higher serum 1,25(OH)₂D₃ predicts lower coronary calcium mass, regardless of race. Blacks have higher serum levels of 1,25(OH)₂D₃ and, as a result, lower quantities of coronary calcium; however, black race in and of itself, independent of serum levels of 1,25(OH)₂D₃, is also associated with lower coronary calcium mass.

View this table: [in this window] [in a new window]   Table 4. Linear Regression Coefficients1

View larger version (23K): [in this window] [in a new window]   Figure 1. The relationship between coronary calcium mass and serum 1,25(OH)2D3 in black () and white () high-risk but asymptomatic subjects. For both races, 1,25(OH)2D3 is inversely related to calcium mass, as indicated by the negative slopes of the regression equations. The similarity of slopes in the regression lines indicates that the relationship between serum 1,25(OH)2D3 and calcium mass is the same for both races. The difference in the y intercepts and the fact that the relationship between coronary calcium mass and 1,25(OH)2D3 is described by distinct regression equations in blacks and whites indicates that although blacks have higher levels of 1,25(OH)2D3 (see "Results"), at any given serum level of 1,25(OH)2D3 blacks tend to have less coronary calcium than whites.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
In this report, we demonstrate an inverse relation between serum levels of 1,25(OH)₂D₃ and coronary calcium mass estimated by EBCT in all subjects irrespective of race, implicating a systemic steroid osteoregulatory factor in the regulation of atherosclerotic calcification and confirming our previous results.³⁹ In addition, our data corroborate, quantify, and extend our previous cinefluoroscopic findings¹¹ that blacks have less coronary calcification than whites. Multivariate linear regression analysis indicates that serum levels of 1,25(OH)₂D₃ and black ethnicity are independently and inversely related to coronary calcium mass. However, racial differences in coronary calcification remain that cannot be attributed solely to quantitative differences in vitamin D metabolism, as demonstrated by the lack of significance of the interaction term of racex1,25(OH)₂D₃ on coronary calcium mass in multivariate regression. Although blacks have less coronary calcium mass and higher serum levels of 1,25(OH)₂D₃ than whites, the relationship between serum levels of 1,25(OH)₂D₃ and coronary calcium mass is the same for both races (as indicated by the similarity of the regression line slopes in the Figure). Therefore, other as-yet-unidentified factors remain that contribute to decreased coronary calcium mass in blacks.

Although we did not directly measure atherosclerosis or coronary artery disease severity, our data cannot readily be explained by postulating less atherosclerosis in blacks. Black and white subjects in our study had similar risk factor profiles and Framingham risk (Table 1 and "Results"); moreover, our black subjects had higher numbers of coronary events during clinical follow-up.^{11 12} Furthermore, in contrast to older studies,^{41 42 43 44 45} more recent postmortem data indicate that there is little difference in the extent of coronary atherosclerosis between blacks and whites,⁴⁶ yet the quantity of coronary calcification is less in blacks than in whites.^{47 48 49} In one study, for example, aortic plaques in whites were calcified 1.6 times more frequently than in blacks with the same types of lesions.⁵⁰ Collectively, these pathological studies suggest that coronary calcium mass in blacks is less than that in whites, and they are consistent with both the EBCT findings reported here and our previous cinefluoroscopic results.¹¹

Our data provide no direct explanation for our findings of less coronary calcium mass in blacks. However, in view of our observation that serum levels of 1,25(OH)₂D₃ are inversely related to calcium mass (Reference 39³⁹ and this report), it is conceivable that ethnic differences in genetic and/or endocrine mechanisms may be contributing factors; data from several sources suggest this possibility. Tentolouris et al⁵¹ reported a familial syndrome of aortic calcification in the absence of aortic or coronary atherosclerosis, suggesting that atherosclerosis and calcification may be genetically distinct yet related processes. More direct evidence implicating genetic determinants for calcification has been obtained recently in a transgenic murine model of atherosclerosis.^{52 53} Several studies have demonstrated racial differences in endocrine factors that affect bone metabolism and that could also affect atherosclerotic calcification. For example, in addition to alterations in the vitamin D–endocrine system,^{27 54} racial differences in levels of growth hormone,⁵⁵ parathyroid hormone,⁵⁴ estrogen,⁵⁶ and testosterone⁵⁷ have been reported. Thus, it seems plausible to speculate that the ethnic differences in coronary calcium reported here as well as previously¹¹ may have at least in part a genetic and/or metabolic basis beyond that attributable to differences in vitamin D metabolism. Further studies are required to elucidate these possibilities.

It is conceivable that some of the coronary calcium we observed was unrelated to atheromatous plaque. Medial calcification of the large arteries unassociated with atherosclerotic disease (Mönckeberg's calcinosis) can be produced in animals by various pharmacological manipulations, including injections or dietary supplementation of large doses of vitamin D.^{58 59 60} Because EBCT is unable to distinguish atherosclerotic calcification from Mönckeberg's medial calcification, we cannot exclude the possibility that some of the calcium we observed was of such nonatherosclerotic origin. However, although medial calcification is observed in peripheral and visceral arteries,⁶¹ available pathological evidence indicates that it occurs only rarely in the coronary arteries.^{1 2 3 62}

Conclusions
Black race and serum levels of 1,25(OH)₂D₃ are independent negative determinants of coronary calcium mass. However, although blacks have higher levels of 1,25(OH)₂D₃ and less coronary calcium mass than whites, the relationship between 1,25(OH)₂D₃ and calcium mass is the same for both races. Diminished quantities of coronary calcium in blacks cannot be accounted for solely by increased 1,25(OH)₂D₃ levels in blacks.

	Acknowledgments

 
This study was supported by NHLBI grants No. 5 RO1 HL-43277-06 and HL-30568, NCRR grant No. MO1 RR 00865, the Kenneth T. and Eileen L. Norris Foundation, and the Saint John's Cardiovascular Research Institute. We would like to extend our gratitude to Bruce H. Brundage, MD, for institutional support and to Ramon M. Valencia for technical and editorial assistance.

Received February 12, 1997; revision received April 2, 1997; accepted April 12, 1997.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Blankenhorn DH. Coronary arterial calcification: a review. Am J Med Sci. 1961;42:1-49.
   
2. Stary HC. The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life. Eur Heart J. 1990;11(suppl E):3-19.
   
3. Wexler L, Brundage B, Crouse J, Detrano R, Fuster V, Maddahi H, Rumberger J, Stanford W, White R. Coronary artery calcification: pathophysiology, epidemiology, imaging methods and clinical implications: a scientific statement from the American Heart Association. Circulation. 1996;94:1175-1192.[Free Full Text]
   
4. Wong ND, Detrano RC, Abrahamson D, Tobis JM, Gardin JM. Coronary artery screening by electron beam computed tomography: facts, controversy, and future. Circulation. 1995;91:632-636.
   
5. Fallavollita JA, Brody AS, Bunnell IL, Kumar K, Canty JM Jr. Fast computed tomography detection of coronary calcification in the diagnosis of coronary artery disease: comparison with angiography in patients <50 years old. Circulation. 1994;89:285-290.[Abstract/Free Full Text]
   
6. Devries S, Wolfkiel C, Fusman B, Bakdash H, Ahmed A, Levy P, Chomka E, Kondos G, Zajac E, Rich S. Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography. J Am Coll Cardiol. 1995;25:76-82.[Abstract]
   
7. Wong ND, Kouwabunpat D, Vo AN, Detrano RC, Eisenberg H, Goel M, Tobis J. Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women: relation to age and risk factors. Am Heart J. 1994;127:422-430.[Medline] [Order article via Infotrieve]
   
8. Detrano RC, Wong ND, Tang W, French WJ, Georgiou D, Young E, Brezden OS, Doherty TM, Narahara KA, Brundage BH. Prognostic significance of cardiac cinefluoroscopy for coronary calcific deposits in asymptomatic high risk subjects. J Am Coll Cardiol. 1994;24:354-358.[Abstract]
   
9. Janowitz WR, Agatston AS, Kaplan G, Viamonte M Jr. 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]
   
10. Kung S, Detrano RC. Are there gender differences regarding coronary artery calcification? Am J Card Imaging. 1996;10:72-77.[Medline] [Order article via Infotrieve]
    
11. Tang W, Detrano RC, Brezden OS, Georgiou D, French WJ, Wong ND, Doherty TM, Brundage BH. Racial differences in coronary calcium prevalence among high risk adults. Am J Cardiol. 1995;75:1088-1091.[Medline] [Order article via Infotrieve]
    
12. Detrano RC, Tang W, Brezden O, Puentes G, Reed J, Grim C. Coronary calcium, race, and coronary heart disease. Circulation. 1996;94 (suppl I):I-738. Abstract.
    
13. Doherty TM, Detrano RC. Coronary arterial calcification as an active process: a new perspective on an old idea. Calcif Tissue Int. 1994;54:224-230.[Medline] [Order article via Infotrieve]
    
14. Bostrom K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest. 1993;91:1800-1809.
    
15. Demer LL, Watson KE, Bostrom K. Mechanism of calcification in atherosclerosis. Trends Cardiovasc Med. 1994;4:45-49.
    
16. Reichel H, Koeffler HP, Norman AW. The role of the vitamin D endocrine system in health and disease. N Engl J Med. 1989;320:980-991.[Medline] [Order article via Infotrieve]
    
17. Fraser DR. Vitamin D. Lancet. 1995;345:104-107.[Medline] [Order article via Infotrieve]
    
18. Bouillon R, Okamura WH, Norman AW. Structure-function relationships in the vitamin D endocrine system. Endocrine Rev. 1995;16:200-257.[Medline] [Order article via Infotrieve]
    
19. Heaney RP. Bone mass, the mechanostat, and ethnic differences. J Clin Endocrinol Metab. 1995;80:2289-2290.[Medline] [Order article via Infotrieve]
    
20. Trotter M, Bronman GE, Peterson RR. Densities of bones of white and negro skeletons. J Bone Joint Surg Am. 1960;42A:50-58.
    
21. Cohn SH, Abesamis C, Yasamura S, Aloia JF, Zanzi I, Ellis KJ. Comparative skeletal mass and radial bone mineral content in black and white women. Metab Clin Exp. 1977;26:171-178.
    
22. Farmer ME, White LR, Brody JA, Bailey KR. Race and sex differences in hip fracture incidence. Am J Public Health. 1984;74:1374-1380.[Abstract/Free Full Text]
    
23. Gyepes M, Mellins HZ, Katz I. The low incidence of fracture of the hip in the Negro. JAMA. 1968;181:557-562.
    
24. Smith RW, Rizek J. Epidemiologic studies of osteoporosis in women of Puerto Rico and southeastern Michigan with special reference to age, race, national origin and to other related or associated findings. Clin Orthop. 1966;45:31-48.[Medline] [Order article via Infotrieve]
    
25. Eck L, Hackett-Renner C. Calcium intake in youth: sex, age and racial differences in NHANES II. Prev Med. 1992;21:473-482.[Medline] [Order article via Infotrieve]
    
26. Weinstein RS, Bell NH. Diminished rates of bone formation in normal black adults. N Engl J Med. 1988;319:1698-1701.[Abstract]
    
27. Bell NH. 25-Hydroxyvitamin D₃ reverses alteration of the vitamin D-endocrine system in blacks. Am J Med. 1995;99:597-599.[Medline] [Order article via Infotrieve]
    
28. Bell NH, Greene A, Epstein S, Oexmann J, Shaw S, Shary S. Evidence for alteration of the vitamin D-endocrine system in blacks. J Clin Invest. 1985;76:470-473.
    
29. Perry HM III, Miller DK, Morley JE, Horowitz M, Kaiser FE, Perry HM Jr, Jensen J, Bentley J, Boyd S, Kraenzle D. A preliminary report of calcium metabolism in older African Americans. J Am Geriatr Soc. 1993;41:612-616.[Medline] [Order article via Infotrieve]
    
30. Brickman AS, Nydy MD, Griffiths RF, von Hungen K, Tuck ML. Racial differences in platelet cytosolic calcium and calcitropic hormones in normotensive subjects. Am J Hypertens. 1993;6:46-51.[Medline] [Order article via Infotrieve]
    
31. M'Buyamba-Kabangu JR, Fagard R, Lijnen P, Bouillon R, Lissens W, Amery A. Calcium, vitamin D-endocrine system, and parathyroid hormone in black and white males. Calcif Tissue Int. 1987;41:70-74.[Medline] [Order article via Infotrieve]
    
32. Clemens TL, Henderson SL, Adams JS, Holick MF. Increased skin pigment reduces the capacity of skin to synthesize vitamin D₃. Lancet. 1982;1:74-76.[Medline] [Order article via Infotrieve]
    
33. Detrano RC, Wong ND, French WJ, Tang W, Georgiou D, Young E, Brezden OS, Doherty T, Brundage BH. Prevalence of fluoroscopic coronary calcific deposits in 1,461 high risk, asymptomatic individuals. Am Heart J. 1994;127:1526-1532.[Medline] [Order article via Infotrieve]
    
34. Anderson K, Wilson P, Odell P, Kannel W. An updated coronary risk profile. Circulation. 1991;83:356-363.[Free Full Text]
    
35. Mahaisavariya P, Detrano RC, Kang X, Garner D, Vo A, Georgiou D, Molloi S, Brundage BH. Quantitation of in vitro coronary artery calcium using ultrafast computed tomography. Cathet Cardiovasc Diagn. 1994;32:387-393.[Medline] [Order article via Infotrieve]
    
36. Detrano RC, Kang X, Mahaisavariya P, Tang W, Colombo A, Molloi S, Garner D, Nickerson S. Accuracy of quantifying coronary hydroxyapatite with electron beam tomography. Invest Radiol. 1994;29:733-738.[Medline] [Order article via Infotrieve]
    
37. Wang S, Detrano RC, Tang W, Doherty TM, Puentes G, Wong N, Brundage BH. Detection of coronary calcification with electron beam computed tomography: evaluation of inter-examination reproducibility and comparison of three image acquisition protocols. Am Heart J. 1996;132:550-558.[Medline] [Order article via Infotrieve]
    
38. Bielak LF, Kaufmann RB, Moll PP, McCollough CH, Schwartz RS, Sheedy PF II. Small lesions in the heart identified at electron beam CT: calcification or noise? Radiology. 1994;192:631-636.[Abstract/Free Full Text]
    
39. Watson KE, Abrolat ML, Malone LL, Hoeg JM, Doherty TM, Detrano RC, Demer LL. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation. In press.
    
40. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano RC. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15:827-832.[Abstract]
    
41. Peery TM, Langsom SM. Incidence of fatal cardiovascular diseases in Charleston, South Carolina. Arch Intern Med. 1939;64:971-987.
    
42. Holman RL, McGill HC Jr, Strong JP, Geer JC. The natural history of atherosclerosis: the early aortic lesions as seen in New Orleans in the middle of the 20th century. Am J Pathol. 1958;34:209-235.
    
43. Wainwright J. Atheroma in the African (Bantu) in Natal. Lancet. 1961;1:366-368.
    
44. Strong JP, McGill HC Jr. The natural history of coronary atherosclerosis. Am J Pathol. 1962;40:37-49.
    
45. Tejeda C, Strong JP, Montenegro MR, Restrepo C, Solberg LA. Distribution of coronary and aortic atherosclerosis by geographic location, race, and sex. Lab Invest. 1968;18:509-526.[Medline] [Order article via Infotrieve]
    
46. Strong JP, Oalmann MC, Newman WP III, Tracy RE, Malcom GT, Johnson WD, McMahan LH, Rock WA, Guzman MA. Coronary heart disease in young black and white males in New Orleans: community pathology study. Am Heart J. 1984;108:747-759.[Medline] [Order article via Infotrieve]
    
47. Strong JP, Richards ML. Cigarette smoking and atherosclerosis in autopsied men. Atherosclerosis. 1976;23:451-476.[Medline] [Order article via Infotrieve]
    
48. Eggen DA, Strong JP, McGill HC Jr. Coronary calcification. relationship to clinically significant coronary lesions and race, sex, and topographic distribution. Circulation. 1965;32:948-955.[Abstract/Free Full Text]
    
49. Blache JO, Handler FP. Coronary artery disease: a comparison of the rates and patterns of development of coronary arteriosclerosis in the negro and white races with its relation to clinical coronary artery disease. Arch Pathol. 1950;50:189-198.
    
50. Strong JP, McGill HC. The natural history of aortic atherosclerosis: relationship to race, sex and coronary lesions in New Orleans. Exp Mol Pathol. 1963(suppl I):15-27.
    
51. Tentolouris C, Kontozoglou T, Toutouzas P. Familial calcification of aorta and calcific aortic valve disease associated with immunologic abnormalities. Am Heart J. 1993;126:904-909.[Medline] [Order article via Infotrieve]
    
52. Qiao J-H, Xie P-Z, Fishbein MC, Kreuzer J, Drake TA, Demer LL, Lusis AJ. Pathology of atheromatous lesions in inbred and genetically engineered mice: genetic determination of arterial calcification. Arterioscler Thromb. 1994;14:1480-1497.[Abstract/Free Full Text]
    
53. Qiao J-H, Fishbein MC, Demer LL, Lusis AJ. Genetic determination of cartilaginous metaplasia in mouse aorta. Arterioscler Thromb Vasc Biol. 1995;15:2265-2272.[Abstract/Free Full Text]
    
54. Bell NH, Greene A, Epstein S, Oexmann J, Shaw S, Shary S. Evidence for alteration of the vitamin D-endocrine system in blacks. J Clin Invest. 1985;76:470-473.
    
55. Wright NM, Renault J, Willi S, Veldhuis JD, Pandey JP, Gordon L, Key LL, Bell NH. Greater secretion of growth hormone in black than in white men: possible factor in greater bone mineral density. J Clin Endocrinol Metab. 1995;80:2291-2297.[Abstract]
    
56. Richards RJ, Svec F, Bai W, Srinivasan SR, Berenson GS. Steroid hormones during puberty: racial (black-white) differences in androstenedione and estradiol—the Bogalusa Heart Study. J Clin Endocrinol Metab. 1992;75:624-631.[Abstract]
    
57. Ross R, Bernstein L, Judd H, Hanisch R, Pike M, Henderson B. Serum testosterone in healthy young black and white men. J Natl Cancer Inst. 1986;76:45-48.
    
58. Hines TG, Jacobson NL, Beitz DC, Littledike ET. Dietary calcium and vitamin D: risk factors in the development of atherosclerosis in young goats. J Nutr. 1985;115:167-178.
    
59. Bajwa GS, Morrison LM, Ershoff BH. Induction of aortic and coronary athero-arteriosclerosis in rats fed a hypervitaminosis D, cholesterol-containing diet. Proc Soc Exp Biol Med. 1971;138:975-982.[Medline] [Order article via Infotrieve]
    
60. Hass GM, Landerholm W, Hemmens A. Production of calcific athero-arteriosclerosis and thromboarteritis with nicotine, vitamin D and dietary cholesterol. Am J Pathol. 1966;49:739-771.[Medline] [Order article via Infotrieve]
    
61. Lachman AS, Spray TL, Kerwin DM, Shugoll GI, Roberts WC. Medial calcinosis of Mönckeberg: a review of the problem and a description of a patient with involvement of peripheral, visceral and coronary arteries. Am J Med. 1977;63:615-622.[Medline] [Order article via Infotrieve]
    
62. Roberts WC, Waller BF. Effect of chronic hypercalcemia on the heart: an analysis of 18 necropsy patients. Am J Med. 1981;71:371-384.[Medline] [Order article via Infotrieve]
    

This article has been cited by other articles:

				R. Mehrotra, D. Kermah, M. Budoff, I. B. Salusky, S. S. Mao, Y. L. Gao, J. Takasu, S. Adler, and K. Norris Hypovitaminosis D in Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 1144 - 1151. [Abstract] [Full Text] [PDF]

				T. J. Wang, M. J. Pencina, S. L. Booth, P. F. Jacques, E. Ingelsson, K. Lanier, E. J. Benjamin, R. B. D'Agostino, M. Wolf, and R. S. Vasan Vitamin D Deficiency and Risk of Cardiovascular Disease Circulation, January 29, 2008; 117(4): 503 - 511. [Abstract] [Full Text] [PDF]

				M. Hravnak, J. Whittle, M. E. Kelley, S. Sereika, C. B. Good, S. A. Ibrahim, and J. Conigliaro Symptom Expression in Coronary Heart Disease and Revascularization Recommendations for Black and White Patients Am J Public Health, September 1, 2007; 97(9): 1701 - 1708. [Abstract] [Full Text] [PDF]

				R. C. Johnson, J. A. Leopold, and J. Loscalzo Vascular Calcification: Pathobiological Mechanisms and Clinical Implications Circ. Res., November 10, 2006; 99(10): 1044 - 1059. [Abstract] [Full Text] [PDF]

				B. I. Freedman, D. W. Bowden, M. M. Sale, C. D. Langefeld, and S. S. Rich Genetic Susceptibility Contributes to Renal and Cardiovascular Complications of Type 2 Diabetes Mellitus Hypertension, July 1, 2006; 48(1): 8 - 13. [Full Text] [PDF]

				M. Cigolini, M. P. Iagulli, V. Miconi, M. Galiotto, S. Lombardi, and G. Targher Serum 25-hydroxyvitamin d3 concentrations and prevalence of cardiovascular disease among type 2 diabetic patients. Diabetes Care, March 1, 2006; 29(3): 722 - 724. [Full Text] [PDF]

				D. E. Bild, R. Detrano, D. Peterson, A. Guerci, K. Liu, E. Shahar, P. Ouyang, S. Jackson, and M. F. Saad Ethnic Differences in Coronary Calcification: The Multi-Ethnic Study of Atherosclerosis (MESA) Circulation, March 15, 2005; 111(10): 1313 - 1320. [Abstract] [Full Text] [PDF]

				P.E. Norman and J.T. Powell Vitamin D, Shedding Light on the Development of Disease in Peripheral Arteries Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 39 - 46. [Abstract] [Full Text] [PDF]

				T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [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]

				D. E. Bild, A. R. Folsom, L. P. Lowe, S. Sidney, C. Kiefe, A. O. Westfall, Z.-J. Zheng, and J. Rumberger Prevalence and Correlates of Coronary Calcification in Black and White Young Adults : The Coronary Artery Risk Development in Young Adults (CARDIA) Study Arterioscler. Thromb. Vasc. Biol., May 1, 2001; 21(5): 852 - 857. [Abstract] [Full Text] [PDF]

				I. B. Salusky and W. G. Goodman Managing phosphate retention: is a change necessary? Nephrol. Dial. Transplant., November 1, 2000; 15(11): 1738 - 1742. [Full Text] [PDF]

				T. M. Doherty, W. Tang, and R. C. Detrano Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factors J. Am. Coll. Cardiol., September 1, 1999; 34(3): 787 - 794. [Abstract] [Full Text] [PDF]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Doherty, T. M. Articles by Detrano, R. C. Search for Related Content PubMed PubMed Citation Articles by Doherty, T. M. Articles by Detrano, R. C.