Background: Use of electronic nicotine delivery devices is increasing but their effects on exercise function are not well-characterized. We hypothesized that treadmill stress test outcomes would differ between chronic electronic cigarette users (“vapers”), combustible cigarette users (“smokers”), and non-smoking/non-vaping controls. Methods: CLUES (HL1393301) was a cross-sectional study of 395 individuals: 164 exclusive vapers (exhaled carbon monoxide [CO] <5 ppm, positive urine NicCheck I), 117 exclusive smokers (CO >5 ppm, positive urine NicCheck I), and 114 non-vaping/non-smoking controls (CO <5 ppm, negative urine NicCheck I). Participants completed a symptom-limited Balke treadmill stress test protocol, a mean (SD) of 91.3 (16.2) minutes after vaping, smoking, or resting. Outcome measures were peak achieved metabolic equivalents (METs), rate-pressure product (RPP, peak heart rate [HR]*systolic blood pressure), HR reserve (peak HR/[220-age]), and 60-second HR recovery (HRR60). Group differences were compared by general linear models with omnibus p-values adjusted for age, race, and sex and with post-hoc t-tests using Bonferroni-corrected p-values. Results: Vapers were 27.4 (10.6) years old (39% female, 86% white) and had vaped for 4.1 (2.7) years (16.3 [30.0] vape-years). Smokers were 42.8 (13.8) years old (44% female, 56% white) and had smoked for 23.0 (13.0) years (28.7 [26.5] pack-years). Controls were 30.8 (11.9) years old (50% female, 69% white). Age, race, and sex-adjusted mean (95% CIs) outcome values by group are in the Figure. Vapers performed worse than controls on all 4 exercise parameters: peak METs (p<0.001), peak RPP (p=0.020), HR reserve (p<0.001), and HRR60 (p=0.025) with intermediate values compared to smokers. Conclusion: Vapers consistently performed worse than controls on 4 treadmill exercise parameters that predict adverse cardiovascular disease outcomes with intermediate values compared to smokers.

Background: The acute cardiovascular effects of electronic nicotine delivery devices (ENDs) have not been well-characterized. We hypothesized differences in acute cardiovascular and autonomic function responses to use of ENDS by chronic ENDs users (“vapers”), use of combustible cigarettes by chronic “smokers,” and no product use among non-smoking/non-vaping controls. Methods: CLUES (HL1393301) was a cross-sectional study of 395 individuals: 164 exclusive vapers (exhaled carbon monoxide [CO] <5 ppm, positive urine NicCheck I test), 117 exclusive smokers (CO >5 ppm, positive urine NicCheck), and 114 non-vaping/non-smoking controls (CO <5 ppm, negative urine NicCheck). We measured systolic and diastolic blood pressure (BP), heart rate (HR), brachial artery diameter, and time domain HR variability (root mean square differences in successive normal intervals [RMSSD]; % adjacent normal intervals >50 ms [PNN50]) before and 15’ after a product use challenge. Linear mixed models were created to predict outcome measures from group, time, and group*time with age, sex, and race as covariates, followed by group contrasts via post-hoc t-tests with Bonferroni-corrected p values. Results: Vapers were a mean (SD) 27.4 (10.6) years old (39% female, 86% white) and had vaped for 4.1 (2.7) years. Smokers were 42.8 (13.8) years old (44% female, 56% white) and had smoked for 23.0 (13.0) years. Controls were 30.8 (11.9) years old (50% female, 69% white). Model-adjusted mean (95% CIs) outcomes and p values for between group differences in challenge responses are in the Figure. Compared to controls, vapers had greater increases in systolic BP, diastolic BP, and HR (all p < 0.002) and greater reductions in brachial artery diameter, RMSSD, and PNN50 (all p < 0.003) than controls, with values similar to smokers. Conclusion: Chronic vapers showed acute increases in BP and HR, vasoconstriction, and reductions in time domain HR variability after using ENDS, similar to cigarette use by smokers.

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Background We aimed to investigate novel grayscale ultrasound characteristics of the carotid and brachial arteries in people with HIV infection before and after starting initial antiretroviral therapy (ART). Methods and Results We performed grayscale ultrasound image analyses of the common carotid artery (CCA) and brachial artery before and after receipt of 1 of 3 randomly allocated ART regimens. We measured arterial wall echogenicity (grayscale median), contrast (gray‐level difference statistic method), and entropy. These measures and their changes were compared with atherosclerotic cardiovascular disease risk factors, measures of HIV disease severity, and inflammatory biomarkers before and after ART. Changes in the grayscale measures were evaluated within and between ART arms. Among 201 ART‐naïve people with HIV, higher systolic blood pressure, higher body mass index, lower CD4+ T cells, and non‐Hispanic White race and ethnicity were associated independently with lower CCA grayscale median. Changes in each CCA grayscale measure from baseline to 144 weeks correlated with changes in soluble CD163: grayscale median (ρ=−0.17; P =0.044), gray‐level difference statistic–contrast (ρ=−0.19; P =0.024), and entropy (ρ=−0.21; P =0.016). Within the atazanavir/ritonavir arm, CCA entropy increased (adjusted β=0.023 [95% CI, 0.001–0.045]; P =0.04), but no other within‐arm changes in grayscale measures were seen. Correlations of brachial artery grayscale measures were weaker. Conclusions In ART‐naïve people with HIV, CCA grayscale ultrasound measures were associated with atherosclerotic cardiovascular disease risk factors and lower grayscale median was associated with lower CD4+ T cells. Reductions in soluble CD163 with initial ART were associated with improvements in all 3 CCA grayscale measures, suggesting that reductions in macrophage activation with ART initiation may lead to less arterial injury. Registration URL: https://clinicaltrials.gov/ ; Unique identifiers: NCT00811954; NCT00851799