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Heart Disease Signal and Low Femoral Density Linked in People With HIV
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
IAS: Interaction of Vascular and Bone Disease in HIV Infected Patients: Coronary Artery Calcification is associated with femoral but not lumbar spine mineral density - (07/19/11) (slides)
Mark Mascolini
Extensive coronary artery calcium, a harbinger of cardiovascular disease, more than doubled the risk of low femoral bone mineral density (BMD) in a study of 681 HIV-positive people in Italy [1]. The study found no association between coronary artery calcium and low spine BMD.
"There is a strong correlation between coronary artery calcium scores and the risk for heart attack and death due to coronary artery disease," according to the American Heart Association [2,3]. Some earlier research found correlations between high coronary artery calcium and low BMD in people without HIV [4,5], but other research found no such correlation [6].
To determine whether such an association exists in people with HIV, researchers in Bologna and Modena simultaneously assessed lumbar and femoral BMD by DEXA and coronary artery calcium by cardiac CT in 812 consecutive HIV-positive people recruited from January 2006 through December 2010. They defined low BMD as below the 25th percentile for the study group, and they defined extensive coronary artery calcium as a score above 100 Agatston units.
Among 681 people with data available for the full analysis, 75 (11%) had a coronary calcium score at or above 100. People with extensive coronary artery calcium were older (average 54.6 versus 46.6, P < 0.001), more likely to be men (88.0% versus 69.6%, P = 0.001), more likely to have diabetes (26.6% versus 7.4%, P < 0.001), and more likely to have hypertension (36% versus 18%, P < 0.001). People with a coronary calcium score at or above 100 had a higher body mass index (25.2 versus 23.7 kg/m(2), P = 0.004), a lower estimated glomerular filtration rate (97 versus 100.7 mL/min/1.73(2), P = 0.003), and a higher 10-year Framingham cardiovascular risk score (11 versus 5, P < 0.001).
Univariate analysis uncovered a trend toward low femoral (thigh) BMD in people with extensive coronary artery calcium (14.3% versus 22.6%, P = 0.10), but there was no such trend for lumbar spine BMD and extensive coronary artery calcium (15% versus 16%, P = 0.95).
To see whether extensive coronary artery calcium predicts low femoral BMD, the researchers constructed a series of multivariate models. Model 1 considered age and gender; model 2 considered age, gender, and traditional cardiovascular risk factors (diabetes, body mass index, 10-year Framingham cardiovascular risk score); model 3 considered all model 2 factors plus HIV-specific factors (CD4 count and current use of tenofovir, tenofovir plus a protease inhibitor, and (separately) tenofovir plus atazanavir); model 4 considered all model 3 factors plus estimated glomerular filtration rate, vitamin D (25-OH-D) deficiency, and intact parathyroid hormone level.
All four models determined that extensive coronary artery calcium, as defined in this study, approximately doubles the risk of low femoral BMD, but the associations reached statistical significance only in models 3 and 4:
--Model 1: odds ratio (OR) 1.73, 95% confidence interval (CI) 0.88 to 3.66, P = 0.10
--Model 2: OR 2.01, 95% CI 0.97 to 4.19, P = 0.06
--Model 3: OR 2.33, 95% CI 1.11 to 4.86, P = 0.02
--Model 4: OR 2.33, 95% CI 1.09 to 4.99, P = 0.02
The researchers believe their results demonstrate an independent association between low BMD and subclinical atherosclerosis, independently of traditional cardiovascular and HIV-specific risk factors, a finding "suggesting an active cross-talk between these two systems." The study yielded no evidence that might explain why coronary artery calcium correlates with femoral but not lumbar spine BMD.
The investigators called for further study "to elucidate the mechanisms that link bone demineralization and coronary artery calcium accrual and whether therapies that impact BMD might also attenuate coronary artery calcium progression in HIV infected patients."
The American College of Cardiology proposes that a coronary artery calcium score of 100 to 400 indicates moderate cardiovascular risk, a score of 400 to 999 signals high risk, and a score of 1000 or higher indicates very high risk [3]. A review of relevant studies determined that people with a coronary artery calcium score in the lowest tertile (0 to 99) had a 0.4% annual risk of myocardial infarction or cardiovascular death, those in the middle tertile (100 to 399) had a 1.3% annual risk, and those in the highest tertile (400 and higher) had a 2.4% annual risk [3].
References
1. Bellasi A, Zona S, Orlando G, et al. Coronary artery calcification is associated with femoral but not with lumbar spine mineral density. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract MOAB0102.
2. CardioSmart. American Heart Association. Guideline: coronary artery calcium scoring. http://www.cardiosmart.org/managecondition/default.aspx?id=912.
3. A Report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain. J Am Coll Cardiol. 2007;49:378-402. http://content.onlinejacc.org/cgi/reprint/49/3/378.pdf.
4. Filgueira A, Carvalho AB, Tomiyama C, et al. Is coronary artery calcification associated with vertebral bone density in nondialyzed chronic kidney disease patients? Clin J Am Soc Nephrol. 2011;6:1456-1462.
5. Wang TK, Bolland MJ, van Pelt NC, et al. Relationships between vascular calcification, calcium metabolism, bone density, and fractures. J Bone Miner Res. 2010;25:2777-2785.
6. Kim KI, Suh JW, Choi SY, et al. Is reduced bone mineral density independently associated with coronary artery calcification in subjects older than 50 years? J Bone Miner Metab. 2011;29:369-376.
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