General Characteristics
A total of 71 subjects were included in the present study (18 controls and 53 asymptomatic HIV-positive patients). The main characteristics of participants are summarised in Table 1 (anthropometrics, CV risk factors, metabolic status, immune-virologic status of HIV+ subjects). No significant differences were found between the two groups in terms of gender distribution, age, and other major risk factors (p>0.05). All enrolled PLWH were free from metabolic syndrome and had no statistically significant differences compared to controls in relation to this issue. Severity of HIV disease was categorized following the Center for Diseases Control and Prevention classification: 20 (38%) patients were in category A2, 10 (19%) patients in category A3, 2 (4%) patients in category B3, 3 (6%) patients in category C2 and 18 (34%) patients in category C3. Median CD4+ nadir before initiation of cART was 181 (IQR: 94-300) cells/μL. During their therapeutic history, 38 of the 53 HIV+ participants received at least one protease inhibitor (PI) for a median of 3 (IQR: 0-14) years, while 23 HIV+ received a nonnucleoside reverse transcriptase inhibitor (NNRTI) for a median of 1 (IQR: 0-9) years. With cART, plasma viremia was undetectable (lower limit of detection of 37 copies/mL) in all HIV+ subjects. The hematocrit value was 35 ± 4% in HIV+ participants and 41 ± 3% in controls (p=0.122). No significant differences were observed regarding Heart Rate (HR) during CCT examination (p=0.211). Al PLWH enrolled were HIV mono-infected subjects.
Parameters
|
HIV-infected
(n=53)
|
Control group
(n=18)
|
p-value (*)
|
General characteristics
|
|
|
|
Male, n (%)
|
45 (85)
|
14 (77)
|
0.129
|
Age, Years
|
48 (42.5-48)
|
55 (44.5-56)
|
0.122
|
BMIa, kg/m2
|
22 (20.3-22)
|
27 (24–32)
|
0.116
|
HRb, bpm
|
67 (±9.1)
|
65 (±11.3)
|
0.211
|
Systolic blood pressure, mmHg
|
119 (±10)
|
114 (±11)
|
0.131
|
Diastolic blood pressure, mmHg
|
75 (±9)
|
67 (±6)
|
0.061
|
Laboratory results
|
|
|
|
Total cholesterol, (mg/dl)
|
189 (177-189)
|
188 (154–201)
|
0.557
|
HDLc, (mg/dl)
|
39 (35-39)
|
54 (46–66)
|
0.046
|
Triglycerides, (mg/dl)
|
101 (78-170)
|
124 (80–177)
|
0.077
|
Other factors
|
|
|
|
Diabetes, n (%)
|
0 (0)
|
0 (0)
|
1.000
|
Smoking, n (%)
|
9 (17)
|
4 (22)
|
0.686
|
Framingham Risk (%)
|
4 (1-6.5)
|
3 (1-5)
|
0.182
|
ASCVD 10 years, calculated risk
|
4.6 (2.7-4.6)
|
4.6 (1.7-3.5)
|
0.286
|
Immune-virologic status
|
|
|
|
Years of therapy, Years
|
9 (6-9)
|
-
|
NAa
|
Years of exposure to HIV infection, Years
|
10 (1-23)
|
-
|
NAa
|
CD4 enrolment (cell/μl)
|
450 (328-750)
|
-
|
NAa
|
CD4 nadir (cell/μl)
|
181 (94-300)
|
-
|
NAa
|
% of PLWHe naïve for cART
|
12.7
|
-
|
NAa
|
HIV-RNA copies/ml in cART treated PLWH
|
<37
|
-
|
NAa
|
HIV-RNA copies/ml in cART naive PLWH
|
55.000
|
-
|
NAa
|
Table 1. Baseline characteristic of the study cohort. Median and interquartile range (IQR: 25%-75%) or mean ± SD are reported for continuous variables. Simple frequencies (n) and percentages are reported for categorical variables. Abbreviations: BMIa, Body mass Index; HRb, Heart Rate; HDLc, High Density Lipoprotein; PLWHd, People living with HIV; NAe, not applicable.
Measurements of Myocardial Extracellular volume fraction
The median ECV value was 27.4% (IQR: 25%-28%) in healthy controls and 31% (IQR: 28%-31%) in HIV+ participants, respectively. In our study population, ECV differed significantly between the two groups (p<0.001), thus indicating the presence of ECV expansion in the myocardium of HIV+ subjects (Fig. 1 a and b).
Figure 1. (a) Frequency histograms of ECV fraction. (b) Boxplot comparing ECV in controls and HIV+ patients: median, interquartile range (25%-75%) and p-value of the Mann-Whitney test for significance are also reported.
ECV values were not affected by patient’s age neither in the HIV+ group (r=0.12, p=0.145. Figure 2 a) or in controls (r=0.11, p=0.102). On the contrary, ECV was found to significantly correlate with the number of years of exposure to HIV infection (r=0.54, p<0.001. Figure 2 b), and the years on cART (r=0.62, p<0.001. Figure 2 c), showing a trend toward ECV expansion over time in HIV infected patients.
Figure 2. Scatter plots and best-fit regression curves (Solid line) with 95% CI bands (shown as dashed lines) of ECV versus age (a), years of therapy (b), and years of exposure to HIV (c) are shown for HIV+ patients. r and p-value are also reported. Red shading denotes the ECV range of the disease zone. Reference intervals are defined from the work of Scully et al. (3).
Based on the years on cART and years of exposure to HIV, all HIV+ patients were divided into three groups: (A) <5 years, (B) 5 to 10 years and (C) >10 years. (There was a significant difference in ECV (ANOVA, p< 0.001) among controls and groups (see table 2).
The multivariable stepwise linear regression showed that the duration of therapy (β was 0.56 (0.33-0.95), p=0.014) and years of HIV infection (β was 0.53(0.4-0.92), p<0.001) were independent predictors of ECV expansion (Table 3).
Parameters
|
Controls
(n=18)
|
<5 y
(A)
|
5-10 y
(B)
|
>10 y
(C)
|
p-value (*)
|
Myocardial ECV (%)
|
27.4 (25-28)
|
-
|
-
|
-
|
-
|
Years of therapy
|
-
|
29 (26-30)
|
30 (27-32)
|
37 (33-39)
|
<0.001
|
Years of exposure to HIV
|
-
|
29 (26-30)
|
31 (28-34)
|
35 (31-39)
|
<0.001
|
Table 2. Myocardial ECV comparisons between control group and HIV-positive patients selected by (A) less than 5 years, (B) from 5 to 10 years and (C) greater than 10 years. Data are shown as Median and interquartile range (IQR: 25%-75%).
Variable
|
Univariate
|
Multivariate
|
R (95% CI)
|
p-value
|
β (95% CI)
|
p-value
|
Intercept
|
25.5 (21-29.5)
|
0.210
|
25.7 (20.2-30)
|
0.062
|
Age
|
0.12 (0.02-0.35)
|
0.805
|
0.42 (0.33-0.89)
|
0.084
|
Gender
|
0.29 (0.13-0.42)
|
0.149
|
0.19 (0.01-0.34)
|
0.122
|
Heart Rate (HR)
|
0.15 (0.01-0.33)
|
0.301
|
1.29 (1.01-1.5)
|
0.062
|
BMI (kg/m2)
|
-0.26 (-0.01-0.2)
|
0.068
|
-
|
-
|
Systolic blood pressure
|
-0.02 (-0.01-0.2)
|
0.278
|
-
|
-
|
Diastolic blood pressure
|
-0.05 (-0.02-0.1)
|
0.191
|
-
|
-
|
Years of Therapy
|
0.62 (0.44-0.96)
|
<0.001
|
0.56 (0.33-0.95)
|
0.014
|
Years of exposure to HIV infection
|
0.54 (0.36-0.90)
|
<0.001
|
0.53 (0.4-0.92)
|
<0.001
|
|
|
|
|
|
|
Table 3. (A) Univariate correlation analyses between ECV and characteristics of the HIV+ population. (B) Multivariate regression models for predictors of ECV expansion. Age, Heart Rate (HR), systolic and diastolic blood pressure, years of therapy and years of exposure to HIV infection were entered in this model. P-values as assessed by Pearson's correlation for normal distributions, Spearman’s correlation for non-normal distributions as well as β estimates and p-values from multivariate regression models are reported.