Vitamin D deficiency is associated with development of subclinical coronary artery disease in HIV-infected African American cocaine users with low Framingham-defined cardiovascular risk

Figures & data

Table 1 Characteristics of study participants by development of subclinical CAD*

Characteristic	Total	Subclinical CAD		P-value
	(n = 119)	No (n = 108)	Yes (n = 11)
Age (years)	45 (45–49)	46 (45–49)	45 (45–48)	0.79
Male (%)	53.8	50.0	90.9	0. 01
Family history of CAD (%)	26.1	27.8	9.1	0.18
Diabetes (%)	2.5	2.8	0.0	1.00
Hypertension (%)	13.5	18.2	13.0	0.64
Cigarette smoking (%)	90.8	90.7	90.9	0.99
Alcohol use (%)	91.6	90.7	100.0	0.29
Years of cocaine use	15.0 (9.0–20.0)	15.0 (8.5–20.0)	15.0 (9.0–20.0)	0.77
Years of HIV infection	17.0 (10.1–21.2)	17.0 (10.3–21.2)	15.7 (6.7–21.4)	0.59
hsCRP ≥ 2 mg/dL (%)	44.1	43.0	54.6	0.46
Vitamin D deficiency (%)	18.5	14.8	54.6	0.005
Serum 25(OH) D (ng/mL)	18 (11–26)	19 (11–26)	9 (7–25)	0.09
Systolic BP (mmHg)	116 (105–129)	119 (109–130)	120 (104–136)	0.66
Diastolic BP (mmHg)	72 (62–79)	72 (62–79)	69 (64–80)	0.86
Glucose (mg/dL)	87 (79–96)	86 (79–94)	89 (76–101)	0.65
BMI	25.5 (21.9–29.2)	25.1 (21.9–29.2)	25.5 (22.8–29.5)	0.58
Baseline CD4 (cells/mm^3)	332 (207–560)	335 (207–561)	331 (202–409)	0.62
Baseline viral load (copies/mL)	5,515 (300–60,000)	3,445 (202–57,110)	39,149 (13,148–82,285)	0.09
eGFR (mL/min/1.73 m^2)	103 (85–118)	103 (84–119)	101 (91–104)	0.68
Total cholesterol (mg/dL)	158 (137–182)	156 (135–182)	161 (151–183)	0.53
LDL-C (mg/dL)	75 (61–92)	74 (59–92)	82 (72–112)	0.23
HDL-C (mg/dL)	51 (42–69)	51 (42–72)	55 (48–60)	0.88
Triglycerides (mg/dL)	110 (85–158)	112 (87–160)	108 (72–138)	0.38
NRTI use (month)	48.0 (17.0–96.0)	49.5 (24.0–92.5)	24.0 (1.9–111.1)	0.49
NNRTI use (month)	0 (0.0–33.0)	0.0 (0.0–31.5)	0.0 (0.0–36.0)	0.80
PI use (month)	36.0 (0.0–72.0)	36.0 (0.0–70.0)	36.0 (5.9–120.0)	0.55
Any ART use (month)	66.0 (30.0–111.1)	65.5 (30.0–104.0)	72.0 (24.0–132.0)	0.57
Framingham risk score (%)	4.0 (3.0–7.0)	4.0 (3.0–7.0)	7.0 (3.0–8.0)	0.11

Note:

* Median (interquartile range) for continuous variables, proportion (%) for categorical variables.

Abbreviations: CAD, coronary artery disease; CD4, CD4 cell count; viral load, HIV RNA quantification; hsCRP, high-sensitivity C-reactive protein; BP, blood pressure; glucose, fasting glucose; BMI, body mass index (kg/m²); eGFR, estimated glomerular filtration rate (mL/min/1.73 m²); LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; serum 25(OH) D, 25-hydroxyvitamin D; ART, antiretroviral therapy; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; HIV, human immunodeficiency virus; RNA, ribonucleic acid.

Figure 1 Kaplan-Meier subclinical CAD-free survival curve by vitamin D deficiency status. Survival curves by vitamin D deficiency status were statistically different (log-rank test, P = 0.002).

Abbreviation: CAD, coronary artery disease.

Table 2 Demographic, laboratory, and clinical factors in relation to risk of development of subclinical CAD. Proportional hazards regression analysis*

Variable	Subclinical CAD
	Crude HR (95% CI)	Adjusted HR (95% CI)
Age (years)	0.98 (0.83–1.14)
Sex
Male	1.00
Female	0.13 (0.02–1.02)
Cigarette smoking
Never	1.00
Ever	0.99 (0.13–7.84)
Alcohol use
No	1.00
Yes	not estimable
Diabetes
No	1.00
Yes	not estimable
Hypertension
No	1.00
Yes	2.13 (0.45–10.1)
Years of HIV infection	0.96 (0.88–1.05)
hsCRP ≥ 2 mg/dL	1.13 (0.34–3.77)
Serum 25(OH) D (ng/mL)	0.95 (0.89–1.02)
Severe vitamin D deficiency	5.32 (1.62–17.5)	5.32 (1.62–17.5)
Systolic BP (mmHg)	1.01 (0.97–1.04)
Diastolic BP (mmHg)	1.01 (0.95–1.06)
Glucose (mg/dL)	1.01 (0.98–1.03)
BMI (kg/m^2)	0.98 (0.88–1.10)
Baseline CD4 count (cells/mm^3)	1.00 (0.99–1.00)
Baseline viral load (copies/mL)	1.18 (0.91–1.53)
Total cholesterol (mg/dL)	1.00 (0.99–1.02)
LDL-C (mg/dL)	1.01 (0.99–1.03)
HDL-C (mg/dL)	0.99 (0.96–1.02)
Triglycerides (mg/dL)	1.00 (0.98–1.01)
NRTI use (months)
Zidovudine	0.00 (0.00–not estimable)
Combivir®	0.95 (0.80–1.12)
Epivir®	0.08 (0.00–not estimable)
Epzicom®	1.00 (0.98–1.02)
Trizivir®	0.69 (0.00–not estimable)
Zerit®	1.00 (0.98–1.03)
Truvada®	1.00 (0.99–1.02)
Viread®	0.61 (0.00–not estimable)
Ziagen®	0.39 (0.00–not estimable)
NNRTI use (month)
Sustiva®	1.00 (0.98–1.02)
Etravirine	0.58 (0.00–not estimable)
Nevirapine	0.15 (0.00–not estimable)
PI use (month)
Crixivan®	0.03 (0.00–not estimable)
Kaletra®	1.00 (0.98–1.03)
Lexiva®	1.01 (0.97–1.03)
Norvir®	1.00 (0.99–1.01)
Prezista®	0.99 (0.93–1.06)
Reyataz®	1.00 (0.99–1.01)
Viracept®	0.14 (0.00–not estimable)
Other ART use (month)
Isentress®	0.90 (0.71–1.13)
Seizentry®	0.71 (0.00–not estimable)
Any ART use (month)	1.00 (0.99–1.01)
Framingham risk score (%)	1.20 (0.97–1.48)

Notes:

* Crude hazards ratios (HRs) were obtained from univariate Cox’s proportional hazards model. The adjusted HRs were obtained from the final Cox’s proportional hazard model. Those factors that were significant at the P ≤ 0.20 level in the univariate Cox’s models were put into an initial multivariate Cox’s proportional hazards regression model to identify factors that were independently associated with development of subclinical CAD. Those variables that ceased to make significant contributions to the models were eliminated in a stagewise manner, yielding a final model. Kaletra®, Abbott Laboratories, Abbott Park, IL, USA; Lexiva®, Glaxo Smith Kline, Brentford, London, UK; Norvir®, AbbVie Inc., North Chicago, IL, USA; Prezista®, Janssen Pharmaceuticals, Inc., Titusville, NJ, USA; Reyataz®, Bristol-Myers Squibb, New York, NY, USA; Viracept®, Agouron Pharmaceuticals Inc., La Jolla, CA, USA.

Abbreviations: CAD, coronary artery disease; CD4, CD4 cell count; viral load, HIV RNA quantification; hsCRP, high-sensitivity C-reactive protein; BP, blood pressure; glucose, fasting glucose; BMI, body mass index (kg/m²); LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; serum 25(OH) D, 25-dihydroxyvitamin D; vitamin D deficiency, serum 25(OH) D <10 ng/mL; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; CI, confidence interval; HIV, human immunodeficiency virus; RNA, ribonucleic acid.

Figure 2 Hazard ratios of subclinical coronary artery disease at different vitamin D levels. The data suggests that there is a threshold level of vitamin D (10 ng/mL) above which the effect of vitamin D on subclinical coronary artery disease is diminished.