Association of C-Reactive Protein and Acute Myocardial Infarction in HIV-Infected PatientsVirginia A. Triant, MD, MPH, James B. Meigs, MD, MPH, and

Steven K. Grinspoon, MD Division of Infectious Diseases (VAT), Program in Nutritional Metabolism (SKG and VAT), and the General Medicine Division (JBM), Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114

• HIV patients had a higher prevalence of elevated CRP (68%) compared to non-HIV patients (46%; P<0.0001)• Elevated CRP was associated with AMI among both HIV (P=0.021) and non-HIV (P<0.0001) patients, in chi-square analyses. • In multivariate regression modeling adjusting for demographic factors, elevated CRP was significantly associated with AMI within both HIV and non-HIV groups (OR 2.48, 95% CI 1.07-6.76, P=0.049 for HIV; OR 2.42, 95% CI 2.22-2.63, P<0.0001 for non-HIV).• In multivariate regression modeling adjusting for demographic factors and common cardiac risk factors, elevated CRP remained associated with AMI within both HIV and non-HIV groups, although the p value indicated a trend for the HIV group (OR 2.24, 95% CI 0.95-6.18, P=0.086 for HIV; OR 2.20, 95% CI 2.02-2.40, P<0.0001 for non-HIV).

• The presence of both elevated CRP and HIV infection increases the risk of AMI by more than four-fold compared to patients with neither elevated CRP nor HIV infection. • AMI risk is increased by approximately two-fold with either elevated CRP or HIV infection, which were shown to be independent of each other. • Elevated CRP and HIV infection remained significant risk factors for AMI after adjusting for demographics and common cardiac risk factors and after limiting the analysis to patients whose most recent CRP preceded AMI by 1 week to 3 years. • There is a higher prevalence of elevated CRP among HIV patients compared to non-HIV patients. • In HIV-stratified analyses, elevated CRP is associated with AMI within both the HIV and non-HIV groups.• AMI rates are higher in HIV compared to non-HIV groups, for patients with CRP available, normal, and elevated.

• Acute myocardial infarction (AMI) and coronary heart disease are more common in HIV versus non-HIV patients. • While traditional cardiac risk factors including hypertension, diabetes, and dyslipidemia have been shown to be prevalent among HIV patients, the role of inflammation and the utility of related biomarkers for cardiac risk prediction has not been studied in this group. • In general populations, inflammation plays a role in the development of AMI, and elevated C-reactive protein (CRP) has been shown to be associated with coronary events.• In patients with a chronic infection and heightened inflammatory state, it is unknown whether CRP adds prognostic information with respect to cardiac events beyond that conferred by HIV status.• We investigated whether elevated CRP and HIV infection are independently associated with AMI.

Figure 1. AMI rates according to HIV status and CRP test resultAMI rates are calculated as the number of patients with an AMI event per 100 persons. Chi square P values for the association of elevated CRP with AMI are shown, in HIV-stratified analyses.

• CRP and HIV are independent risk factors for AMI and together confer a four-fold increased risk. • CRP appears to have independent prognostic power for the prediction of AMI beyond that of HIV infection itself, despite the fact that HIV infection represents a chronic inflammatory state and HIV patients demonstrate increased rates of cardiac risk factors.• The role of inflammation in conferring cardiac risk – and particularly the contribution of acute versus chronic inflammatory states - will be important to further delineate for HIV patients.• HIV patients merit aggressive cardiovascular risk assessment and reduction.• Measurement of CRP may play a role in developing HIV-specific cardiac risk assessment strategies, which will be important for the long-term care of this population.

• Of 1,648,687 patients in the background population, 70,357 (487 HIV and 69,870 non-HIV) patients were included in the analysis.• In univariate analyses, elevated CRP and HIV infection were each independently associated with AMI (Models 1 and 2 in Table 1).• When included together, elevated CRP and HIV infection were each independently associated with AMI (Model 3 in Table 1)• In a fully adjusted model including demographic factors and common cardiac risk factors, elevated CRP and HIV infection remained independently associated with AMI (adjusted odds ratio 2.13 for CRP and 1.93 for HIV; Model 10 in Table 1).• Elevated CRP and HIV infection each conferred an approximate two-fold increased risk of AMI, and together they conferred a more than four-fold increased risk of AMI compared to having neither risk factor.

• Patients were followed longitudinally at one of two hospitals comprising a large U.S. healthcare system, and data were obtained from a clinical care data registry. • Patients with at least one CRP test available between January 1997 and December 2006 were included. • The definition of elevated CRP was based on the normal reference range of the assay.• CRP was restricted to occurring prior to AMI in HIV-stratified analyses. In the combined, updated analysis, CRP was also limited to occurring less than three years and more than one week prior to AMI.• Chi square analysis was used to assess the association of elevated CRP with AMI in HIV-stratified analyses• Multivariate logistic regression analysis was used to test the association of elevated CRP and HIV infection with AMI in the combined analysis.

Contact:

Virginia A. Triant, MD, MPHInfectious Diseases Division

Massachusetts General Hospital55 Fruit St. Boston, MA 02114

vtriant@partners.org

Table 1

Adjusted odds ratios for AMI in multivariate regression modeling of combined HIV and non-HIV patients

Covariate Recent CRP high vs. not HIV vs. non-HIV

  OR (95% CI) P value OR (95% CI) P value

Model 1 (CRP) 2.51 (2.27-2.78) <0.0001    

Model 2 (HIV)     2.07 (1.31-3.10) 0.0009

Model 3 (CRP, HIV) 2.50 (2.26-2.77) <0.0001 1.74 (1.10-2.61) 0.0122

Model 4 (CRP, HIV, age) 2.31 (2.08-2.56) <0.0001 2.29 (1.44-3.45) 0.0002

Model 5 (CRP, HIV, age, gender) 2.34 (2.11-2.59) <0.0001 2.15 (1.35-3.25) 0.0006

Model 6 (CRP, HIV, age, gender, race) 2.27 (2.05-2.52) <0.0001 1.86 (1.16-2.81) 0.0056

Model 7 (CRP, HIV, age, gender, race, hypertension) 2.23 (2.01-2.47) <0.0001 1.97 (1.23-2.99) 0.0025

Model 8 (CRP, HIV, age, gender, race, diabetes) 2.14 (1.93-2.38) <0.0001 1.83 (1.15-2.77) 0.0068

Model 9 (CRP, HIV, age, gender, race, dyslipidemia) 2.43 (2.19-2.70) <0.0001 1.91 (1.20-2.89) 0.0037

Model 10 (CRP, HIV, age, gender, race, hypertension, diabetes, dyslipidemia)

2.13 (1.92-2.37) <0.0001 1.93 (1.21-2.93) 0.0035

Table 2. Characteristics of patients according to HIV status and CRP test status and result

  HIV Non-HIV

  BackgroundCRP

AvailableNormal

CRPElevated

CRP Background CRP AvailableNormal

CRP Elevated CRP

(N=7099) (N=503) (N=159) (N=344) (N=1641588) (N=70846) (N=38520) (N=32326)

HTN 1689 (23.8) 189 (37.6) 54 (34.0) 135 (39.2) 257257 (15.7) 33425 (47.2) 16888 (43.8) 16537 (51.2)

DM 1140 (16.1) 110 (21.9) 31 (19.5) 79 (23.0) 108765 (6.6) 11930 (16.8) 4954 (12.9) 6976 (21.6)

Lipids 1893 (26.7) 178 (37.2) 76 (47.8) 111 (32.3) 244175 (14.9) 37139 (52.4) 22691 (58.9) 14448 (44.7)

AMI 423 (6.0) 38 (7.6) 6 (3.8) 32 (9.3) 52535 (3.2) 2537 (3.6) 816 (2.1) 1722 (5.3)

RESULTS OF COMBINED ANALYSIS (HIV AND NON-HIV)

RESULTS OF HIV-STRATIFIED ANALYSES

BACKGROUND CONCLUSIONS

METHODS IMPLICATIONS

P<0.0001

P=0.021

00.010.020.030.040.050.060.070.080.090.1

HIV Non-HIV

AM

I Ev

en

ts P

er

10

0 P

ers

on

s

CRP Normal CRP Elevated