Background:  Cardiovascular disease (CVD) is a major problem for chronically treated HIV patients. Episodic use of antiretroviral therapy (ART) (DC group) was associated with increased CVD risk compared to continuous ART (VS group) in the SMART Study. N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) is a marker for the diagnosis and prognosis of heart failure; in the general population, it is a significant predictor of CVD. Our goal was to quantify the risk of CVD events associated with NT-proBNP at baseline in the SMART study.

Methods:  NT-proBNP was measured at baseline in 186 patients who experienced a CVD event and in 329 matched controls. NT-proBNP assays were performed by electrochemiluminescence immunoassay. Odds ratios (OR) with 95 % confidence intervals (CI) for CVD events for quartiles and for 1 log higher levels of NT-proBNP were estimated using conditional logistic regression unadjusted and adjusted for baseline covariates: age, race, CD4⁺ count, HIV RNA and ART status, smoking, total/HDL cholesterol, prior CVD, diabetes, use of blood pressure lowering drugs, BMI, hepatitis B/C co-infection, and major baseline ECG abnormalities. In a separate model, OR were also adjusted for baseline levels of D-dimer, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP).

Results:  At baseline median NT-proBNP (Inter-Quartile Range, IQR) was 48.1 (18.5 to 112.9) pg/mL in HIV patients who developed a CVD event and 25.7 (12.4 to 50.2) pg/mL in controls. The OR for the highest quartile (37.1% of cases and 18.2% of controls) versus the lowest quartile (17.2% of cases and 29.2% of controls) was 3.7 (95%CI: 2.1 to 6.5; P <0.001). The OR per 1 log_e higher NT-proBNP for CVD events was 1.5 (95%CI, 1.3 to 1.8; P <0.001). After adjustment for baseline covariates, these OR were 2.8 (95%CI 1.4 to 5.6; P =0.003) and 1.4 (95%CI 1.1 to 1.7; P =0.002), respectively. After adjustment for covariates that also included baseline levels of log_e D-dimer, IL-6, and hsCRP, the OR were 2.3 (P =0.02) and 1.2 (P =0.07). The association of NT-proBNP with CVD was similar for the DC and VS groups.

Conclusions:  Higher levels of NT-proBNP are associated with increased risk for CVD events in HIV patients, potentially due to up-regulation of the expression of NT-proBNP in the setting of HIV-induced subclinical vascular disease and increased myocardial strain. Further studies are warranted if NT-proBNP can be used for early detection of CVD in HIV patients and if ART influences NT-proBNP levels.