Jayanthi Vijayakumar

Arterial inflammation in patients with HIV

CONTEXT Cardiovascular disease is increased in patients with human immunodeficiency virus (HIV), but the specific mechanisms are unknown. OBJECTIVE To assess arterial wall inflammation in HIV, using 18fluorine-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET), in relationship to traditional and nontraditional risk markers, including soluble CD163 (sCD163), a marker of monocyte and macrophage activation. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study of 81 participants investigated between November 2009 and July 2011 at the Massachusetts General Hospital. Twenty-seven participants with HIV without known cardiac disease underwent cardiac 18F-FDG-PET for assessment of arterial wall inflammation and coronary computed tomography scanning for coronary artery calcium. The HIV group was compared with 2 separate non-HIV control groups. One control group (n = 27) was matched to the HIV group for age, sex, and Framingham risk score (FRS) and had no known atherosclerotic disease (non-HIV FRS-matched controls). The second control group (n = 27) was matched on sex and selected based on the presence of known atherosclerotic disease (non-HIV atherosclerotic controls). MAIN OUTCOME MEASURE Arterial inflammation was prospectively determined as the ratio of FDG uptake in the arterial wall of the ascending aorta to venous background as the target-to-background ratio (TBR). RESULTS Participants with HIV demonstrated well-controlled HIV disease (mean [SD] CD4 cell count, 641 [288] cells/μL; median [interquartile range] HIV-RNA level, <48 [<48 to <48] copies/mL). All were receiving antiretroviral therapy (mean [SD] duration, 12.3 [4.3] years). The mean FRS was low in both HIV and non-HIV FRS-matched control participants (6.4; 95% CI, 4.8-8.0 vs 6.6; 95% CI, 4.9-8.2; P = .87). Arterial inflammation in the aorta (aortic TBR) was higher in the HIV group vs the non-HIV FRS-matched control group (2.23; 95% CI, 2.07-2.40 vs 1.89; 95% CI, 1.80-1.97; P < .001), but was similar compared with the non-HIV atherosclerotic control group (2.23; 95% CI, 2.07-2.40 vs 2.13; 95% CI, 2.03-2.23; P = .29). Aortic TBR remained significantly higher in the HIV group vs the non-HIV FRS-matched control group after adjusting for traditional cardiovascular risk factors (P = .002) and in stratified analyses among participants with undetectable viral load, zero calcium, FRS of less than 10, a low-density lipoprotein cholesterol level of less than 100 mg/dL (<2.59 mmol/L), no statin use, and no smoking (all P ≤ .01). Aortic TBR was associated with sCD163 level (P = .04) but not with C-reactive protein (P = .65) or D-dimer (P = .08) among patients with HIV. CONCLUSION Participants infected with HIV vs noninfected control participants with similar cardiac risk factors had signs of increased arterial inflammation, which was associated with a circulating marker of monocyte and macrophage activation.

Positron emission tomography measurement of periodontal 18F-fluorodeoxyglucose uptake is associated with histologically determined carotid plaque inflammation.

OBJECTIVES This study aimed to test the hypothesis that metabolic activity within periodontal tissue (a possible surrogate for periodontal inflammation) predicts inflammation in a remote atherosclerotic vessel, utilizing (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging. BACKGROUND Several lines of evidence establish periodontal disease as an important risk factor for atherosclerosis. FDG-PET imaging is an established method for measuring metabolic activity in human tissues and blood vessels. METHODS One hundred twelve patients underwent FDG-PET imaging 92 ± 5 min after FDG administration (13 to 25 mCi). Periodontal FDG uptake was measured by obtaining standardized uptake values from the periodontal tissue of each patient, and the ratio of periodontal to background (blood) activity was determined (TBR). Standardized uptake value measurements were obtained in the carotid and aorta as well as in a venous structure. Localization of periodontal, carotid, and aortic activity was facilitated by PET coregistration with computed tomography or magnetic resonance imaging. A subset of 16 patients underwent carotid endarterectomy within 1 month of PET imaging, during which atherosclerotic plaques were removed and subsequently stained with anti-CD68 antibodies to quantify macrophage infiltration. Periodontal FDG uptake was compared with carotid plaque macrophage infiltration. RESULTS Periodontal FDG uptake (TBR) is associated with carotid TBR (R = 0.64, p < 0.0001), as well as aortic TBR (R = 0.38; p = 0.029). Moreover, a strong relationship was observed between periodontal TBR and histologically assessed inflammation within excised carotid artery plaques (R = 0.81, p < 0.001). CONCLUSIONS FDG-PET measurements of metabolic activity within periodontal tissue correlate with macrophage infiltration within carotid plaques. These findings provide direct evidence for an association between periodontal disease and atherosclerotic inflammation.

Imaging of the Aortic Valve Using Fluorodeoxyglucose Positron Emission Tomography: Increased Valvular Fluorodeoxyglucose Uptake in Aortic Stenosis

OBJECTIVES Because fluorodeoxyglucose positron emission tomography (FDG-PET) imaging provides a noninvasive index of inflammation, we sought to assess whether FDG uptake in the aortic valve (AV) is increased in aortic stenosis (AS). BACKGROUND AS is associated with valvular inflammation. METHODS FDG-PET/computed tomography data were retrospectively evaluated in 84 patients (age 73 ± 9 years, 45% female), 42 patients with AS, and 42 age-matched controls. FDG uptake was determined within the AV while blinded to AS severity. Target-to-background ratio (TBR) was calculated as valvular/blood activity. Stenosis severity was established on echocardiography, and presence of AV calcification was independently assessed on computed tomography. RESULTS The aortic valve PET signal (TBR) was increased in AS compared with controls (median 1.53 [interquartile range (IQR): 1.42 to 1.76] vs. 1.34 [IQR: 1.20 to 1.55]; p < 0.001). Further, compared with controls, TBR was increased in mild (median 1.50 [IQR: 1.36 to 1.75]; p = 0.01) and moderate (median 1.70 [IQR: 1.52 to 1.94]; p < 0.001), but not in severe AS (median 1.49 [IQR: 1.40 to 1.54]; p = 0.08). When subjects were categorized according to AV calcification, valvular FDG uptake was increased in mildly (median 1.50 [IQR: 1.36 to 1.79]; p < 0.01) and moderately (median 1.67 [IQR: 1.50 to 1.85]; p < 0.001), but not severely calcified valves (median 1.51 [IQR: 1.38 to 1.54]; p = 0.15), compared with noncalcified valves (median 1.35 [IQR: 1.20 to 1.52]). CONCLUSIONS This study supports the hypothesis that AS is an inflammatory condition and suggests that inflammation may be reduced in late-stage disease. This may have important implications in the design of studies assessing the effect of therapeutic agents in modifying progression of AS.

HIGH DOSE ATORVASTATIN REDUCES PERIODONTAL ACTIVITY IN PROPORTION TO ATHEROSCLEROTIC INFLAMMATION: A POTENTIALLY NOVEL PLEIOTROPIC EFFECT OF STATINS

Periodontal disease (PD) is a common, chronic oral inflammatory condition and a risk factor for atherosclerosis (Athero). Here, we assessed whether high-dose atorvastatin (ATV) reduces periodontal (perio) inflammation (using 18F-fluorodeoxyglucose-positron emission tomography/computed tomography [

INFLAMMATION IS INCREASED IN NON-CALCIFIED / MIXED LEFT MAIN CORONARY PLAQUES AND IS MODIFIABLE BY STATINS: A MULTI-CENTER PET-CT STUDY

Non-calcified or mixed coronary plaques without dense calcification (NCP/MP) are associated with increased atherothrombosis risk. Here we tested the hypothesis that atorvastatin (atorva) results in a reduction in left main (LM) inflammation within NCP/MP. Adults with risk factors for or with