Association between abdominal aortic calcifications, cardiovascular disease and bone disease in a cohort of HIV positive patient
Background:
Cardiovascular and bone comorbidities are an important health problem for HIV patients. Numerous studies involving mixed cohorts of HIV-negative patients have shown a strong association between abdominal aortic calcification ( AAC ) marker of cardiovascular disease and the presence of vertebral fractures , but there are no data in the population with HIV infection . The aim of our study was to evaluate the presence and distribution of abdominal aortic calcification in a cohort of patients with HIV infection and its correlation with cardiovascular disease and bone disease, identifying the clinical and immunological factors associated with the presence of AAC
.
In this cross sectional study, 280 asymptomatic HIV positive pts from the SPID (\u201cSan Paolo\u201d Infectious Diseases) cohort were submitted to lateral spine X-ray and DXA. AAC was identified using the AAC-8 score, which estimates the total length of calcification of the anterior and posterior aortic walls in front of vertebrae L1 to L4. Low BMD was defined by T-score or Z-score <-1 at lumbar spine or femoral neck. Vertebral fractures (VF) were identified by morph-metric analysis of X-ray and were defined by the \u201cspine deformity index\u201d(SDI) 651 according to semiquantitative method by Genant. Associations between AAC, BMD and SDI were evaluated by univariate and multivariate logistic regression models. The relationship between the grade of AAC and SDI was evaluate by Spearman\u2019s correlation.
Results:
215/280 patients with HIV infection ( 76.8 % ) did not present AAC ( AAC- : score = 0 AAC - 8 score) and 65/280 ( 23.2 % ) presented AAC ( AAC + : 651 score AAC - 8 score) ;of these 15 pts showed moderate/severe calcifications (AAC>2).
Univariate statistical analysis of demographic parameters , HIV - related and of comorbidities showed that AAC is associated with the following variables : age : OR 3.81 ( 95% CI 2.64-5.51 ), p < .001 ; BMI) : OR 1.07 ( 95% CI, 1:00 to 1:14 ), p = .02 ; Nadir CD4 : OR 0.89 ( 95% CI 0.82-0.97 ), p = .01 ; years of AIDS diagnosis : OR 2.13 ( 95% CI, 1:11 to 4:08 ), p = .02 ; HAART therapy ( vs naive ) : OR 2.75 ( 95% CI 1.28-5.90 ) p = .009. As for comorbidities, in addition to the well- known association between AAC and cardiovascular disease (hypertension : OR 3.67 ( 95% CI, 1:39 to 9:07 ), p = .008 ; cIMT or plaque increase : OR 4.96 ( 95% CI, 2:59 to 9:50 ) p < .001 ) in our analysis AAC is associated with the reduction of GFR below 60 ml / min / 1.73 m2 : 4:39 OR ( 95% CI 1.14-16.88 ) p = 0.03 ; reduction in bone mineral density : 2:45 OR ( 95% CI, 1:32 to 4:54 ), p = 0.042 , and the presence of vertebral fractures ( SDI 651 ) OR 2.17 ( 95% CI, 1:10 to 4:16 ), p = 0.02 .
Multivariate analysis for the study of the factors independently associated with the presence of AAC showed that only age and the presence of thickening cIMT or carotid plaque were significantly associated with the presence of abdominal aortic calcification ( p < . 0001 and p = 0.01 , respectively )
Univariate statistical analysis of T - cell immunophenotypes showed an association between AAC and the following immunophenotypes CD8 + T lymphocytes : CD8 + CD127 + ( absolute values ) indicative of central memory cells ( AAC- : 377 cells / mmc , IQR 264- 540 ; AAC + : 434 cells / mmc , IQR : 336-698 ; p = 0.007 ) ; CD45R0 + CD8 + (percentages and absolute values ) expressed by memory T lymphocytes ( AAC- : 11 % , IQR 8-18 ; AAC + : 16.5 % , IQR : 9-21 ; AAC- : 204 cells / mmc , IQR 130- 320 ; AAC + : 269 cells / mmc IQR 167-444 ; p = 0.04 and p = 0.01 , respectively ) .
AAC 651 predict VF independently from BMD, vitamin D status and bone turn-over marker ( p = 0.01) .
The grade of AAC was directly correlated with the grade of SDI (AAC>2 determines a sixfold increase in the risk of VF (HR 6.44 [IC95% 2.21-18.79], p=.0006).
Furthermore in our HIv population levels of OCP were significantly ( p = 0.025 ) higher in the blood of subjects and AAC + with reduced BMD ( median 1.8 % , IQR 1.3-2.75 ) than in subjects with normal BMD and AAC + ( 1:09 median % ; IQR 0.98-1.34 ) ( p <0.05 ) both in comparison to AAC- individuals and with reduced BMD ( median 1.225 % ; IQR 1:06 to 1:34 ) ( p <0.05 ) .
Conclusions:
In our HIV population AAC resulted associated with cardiovascular and bone comorbidities. This suggests the possibility to use the AAC as a clinical marker for the early identification of individuals at increased risk of developing these diseases . Therefore the detection of calcifications ( to be found with special care in elderly HIV patients) in the survey X-ray of the spine , should necessarily be followed by a careful bone study in order to highlight the possible presence of vertebral fracture or low bone mineral density
