Acute inflammation elicits decreased blood pressure but similar arterial stiffness in young African American adults.

African Americans (AA) have a higher risk for cardiovascular disease (CVD) as compared to their White (W) counterparts. CVD is characterized by increased blood pressure (BP), arterial stiffness and systemic inflammation. An acute inflammatory stimulus may explain physiological manifestations responsible for amplified CVD in AA that are not apparent at rest. The purpose of this study was to evaluate central and peripheral BP, central and local arterial stiffness, and indices of pulse wave morphology in young healthy AA and W participants in response to acute inflammation. Concentrations of the inflammatory cytokine interleukin-6 (IL-6) and measures of central and peripheral BP, central arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)), local carotid arterial stiffness (ß-stiffness, elastic modulus (Ep)), and indices of pulse wave morphology were assessed in 28 participants (21 ± 2 years, AA: n = 11) at baseline (BL), 24 h and 48 h post-inflammation. Changes in IL-6 concentrations (ΔIL-6) were significantly greater at 24 h as compared to 48 h post-inflammation (0.652 ± 0.644 vs. -0.146 ± 0.532 pg/µl, P ≤ 0.0001). Among AA participants, central and peripheral diastolic BP were significantly decreased at 24 h post-inflammation as compared to BL (aortic diastolic BP: -4 ± 4 mmHg, P = 0.016; brachial diastolic BP: -4 ± 4 mmHg, P = 0.014). AA participants also experienced a significant decrease in central and peripheral mean arterial BP at 48 h post-inflammation as compared to BL (aortic mean arterial pressure: -4 ± 4 mmHg, P = 0.009; brachial mean arterial pressure: -4 ± 4 mmHg, P = 0.012). Despite haemodynamic changes, there were no differences in central or local carotid arterial stiffness or indices of pulse wave morphology.

Continuous Glucose Monitoring-Guided Insulin Administration in Hospitalized Patients With Diabetes: A Randomized Clinical Trial.

OBJECTIVE: The efficacy and safety of continuous glucose monitoring (CGM) in adjusting inpatient insulin therapy have not been evaluated. RESEARCH DESIGN AND METHODS: This randomized trial included 185 general medicine and surgery patients with type 1 and type 2 diabetes treated with a basal-bolus insulin regimen. All subjects underwent point-of-care (POC) capillary glucose testing before meals and bedtime. Patients in the standard of care (POC group) wore a blinded Dexcom G6 CGM with insulin dose adjusted based on POC results, while in the CGM group, insulin adjustment was based on daily CGM profile. Primary end points were differences in time in range (TIR; 70-180 mg/dL) and hypoglycemia (<70 mg/dL and <54 mg/dL). RESULTS: There were no significant differences in TIR (54.51% ± 27.72 vs. 48.64% ± 24.25; P = 0.14), mean daily glucose (183.2 ± 40 vs. 186.8 ± 39 mg/dL; P = 0.36), or percent of patients with CGM values <70 mg/dL (36% vs. 39%; P = 0.68) or <54 mg/dL (14 vs. 24%; P = 0.12) between the CGM-guided and POC groups. Among patients with one or more hypoglycemic events, compared with POC, the CGM group experienced a significant reduction in hypoglycemia reoccurrence (1.80 ± 1.54 vs. 2.94 ± 2.76 events/patient; P = 0.03), lower percentage of time below range <70 mg/dL (1.89% ± 3.27 vs. 5.47% ± 8.49; P = 0.02), and lower incidence rate ratio <70 mg/dL (0.53 [95% CI 0.31-0.92]) and <54 mg/dL (0.37 [95% CI 0.17-0.83]). CONCLUSIONS: The inpatient use of real-time Dexcom G6 CGM is safe and effective in guiding insulin therapy, resulting in a similar improvement in glycemic control and a significant reduction of recurrent hypoglycemic events compared with POC-guided insulin adjustment.

Arterial stiffness and blood pressure are similar in naturally menstruating and oral contraceptive pill-using women during the higher hormone phases.

NEW FINDINGS: What is the central question of this study? Are there differences in blood pressure, arterial stiffness and indices of pressure waveforms between young oral contraceptive pill-using and naturally menstruating women during lower and higher hormone phases of their cycles? What is the main finding and its importance? Blood pressure, arterial stiffness and indices of pressure waveforms are influenced similarly by exogenous and endogenous hormones. However, lower levels of exogenous hormones moderately increase blood pressure among oral contraceptive pill-using women. ABSTRACT: Elevations in blood pressure (BP) are understood as having a bidirectional relationship with stiffening of central and peripheral arteries. Arterial stiffness is mitigated by oestrogen, which aides in arterial vasorelaxation. To evaluate whether BP, stiffness, and pressure waveforms were different between young healthy naturally menstruating (non-OCP) and oral contraceptive pill (OCP)-using women, we measured brachial and aortic BPs, carotid-to-femoral pulse wave velocity, carotid ß-stiffness, elastic modulus, central augmentation index and augmentation index normalized to a heart rate of 75 bpm, and forward and backward pressure waveforms in 22 women (22 (1) years, OCP: n = 12). To assess phasic differences, women were studied during the early follicular (≤5 days of menstruation onset) and early luteal (4 (2) days post-ovulation) phases of non-OCP and compared to the placebo pill (≤5 days of onset) and active pill (≤5 days of highest-dose active pill) phases of OCP. During the lower hormone phases, OCP users had significantly higher brachial systolic blood pressure (SBP) (119.3 (8.3) vs. 110.2 (8.3) mmHg, P = 0.02) and aortic SBP (104.10 (7.44) vs. 96.80 (6.39) mmHg, P = 0.03) as compared to non-OCP users; however, during the higher hormone phases, there were no differences in measures of brachial or aortic BP, arterial stiffness, or indices of BP waveforms between OCP and non-OCP users (P ≥ 0.05). In conclusion, exogenous and endogenous hormones have similar influences on BP and arterial stiffness; however, lower levels of exogenous hormones augment both central and peripheral BPs.

Similar inflammatory response and conduit artery vascular function between sexes following induced inflammation.

NEW FINDINGS: What is the central question of this study? Are there sex differences in vascular function following induced inflammation when oestrogen is typically similar between sexes? What is the main finding and its importance? The present study suggests no sex differences in conduit artery vascular responses to acutely induced inflammation during the low-oestrogen phase of the menstrual cycle in premenopausal women. However, women exhibit lower microvascular function than men. Overall, the results underpin the role of oestrogen in previously observed sex differences and the importance of reporting the phase in the hormonal cycle when women are studied. ABSTRACT: Sex differences in cardiovascular disease incidence in premenopausal women and age-matched men have been attributed to the cardioprotective influence of oestrogen. However, limited knowledge exists regarding sex differences following acute inflammation when oestrogen concentrations are lower in women. We evaluated sex differences in vascular responses to induced inflammation when oestrogen concentrations are typically lower in women (early follicular phase or placebo phase of hormonal contraception). In 15 women and 14 men, interleukin-6 (IL-6) concentrations and vascular function [via brachial artery flow-mediated dilatation (FMD)] were assessed at baseline (BL) and 24 (24H) and 48 hours (48H) after administration of influenza vaccine. After induction of inflammation, both sexes exhibited an increase in IL-6 concentrations at 24H [mean (SD) BL vs. 24H: women, 0.563 (0.50) vs. 1.141 (0.65) pg/ml; men, 0.385 (0.17) vs. 1.113 (0.69) pg/ml; P < 0.05] that returned to near-baseline concentrations by 48H (BL vs. 48H, P > 0.05). There were no sex differences in FMD, allometrically scaled FMD or IL-6 concentrations at any time point (P > 0.05). Notably, women exhibited significantly lower microvascular function than men at every time point [P < 0.05; reactive hyperaemic area under the curve (in arbitrary units): women, BL 35,512 (14,916), 24H 34,428 (14,292) and 48H 39,467 (13,936); men, BL 61,748 (27,324), 24H 75,028 (29,051) and 48H 59,532 (13,960)]. When oestrogen concentrations are typically lower in women, women exhibit a similar inflammatory response and conduit artery function, but lower microvascular response to reactive hyperaemia, in comparison to age-matched men.

Interleukin-6 is higher in naturally menstruating women compared with oral contraceptive pill users during the low-hormone phase.

Endogenous sex hormone concentrations vary between healthy naturally menstruating (non-OCP) and oral contraceptive pill-using (OCP) women, as well as across cycles. The aim of this study was to investigate potential differences in concentrations of inflammatory cytokine interleukin-6 (IL-6) and vasoconstrictive substance endothelin-1 (ET-1) and measures of vascular function among relatively lower- and higher-hormone phases of non-OCP and OCP women. Concentrations of estrogen, progesterone, IL-6, and ET-1 and measures of vascular function were collected in 22 women (22 ± 1 yr, OCP: n = 12) during the early follicular (EF, ≤5 days of menstruation onset) and early luteal (EL, 4 ± 2 days postovulation) phases of non-OCP subjects and were compared to the placebo pill (PP, ≤5 days of PP onset) and active pill (AP, ≤5 days of highest-dose AP) phases of OCP subjects. Vascular function was assessed via brachial artery flow-mediated dilation (%FMD). Concentrations of endogenous estrogen and progesterone were higher in the EL phase compared with the EF phase of non-OCP (P = 0.01) but were similar between phases of OCP (P > 0.05). IL-6 was higher in non-OCP during the EF phase compared with the EL phase (P = 0.03) as well as compared with OCP during the PP phase (P = 0.002) but was similar between groups during the EL and AP phases, respectively (P > 0.05). Concentrations of ET-1 and measures of %FMD were similar between groups and unaffected by phase (P > 0.05). Thus, there exists variation in inflammation between young, healthy non-OCP and OCP women during the lower-hormone phase, despite similarities in vascular function and concentrations of ET-1 between groups and phases.NEW & NOTEWORTHY We demonstrate that despite having similar macrovascular function and concentrations of the vasoconstrictive substance endothelin-1 (ET-1) healthy naturally menstruating women display higher concentrations of circulating IL-6 during the lower-hormone phase of their menstrual cycle compared with 1) the higher-hormone phase of their menstrual cycle and 2) the lower-hormone phase of healthy women using oral contraceptive pills.

Race-specific changes in endothelial inflammation and microRNA in response to an acute inflammatory stimulus.

Both aberrant vascular reactivity to acute cardiovascular stress and epigenetic mechanisms such as microRNA (miR) may underlie the increased propensity for African Americans (AA) to develop cardiovascular disease. This study assessed racial differences in acute induced endothelial inflammation and related miRs. Cultured human umbilical vein endothelial cells (HUVECs) derived from AA and Caucasian Americans (CA) were exposed to influenza vaccine to determine changes in inflammatory markers, endothelial nitric oxide synthase (eNOS), and miR expression/release. Endothelial function [flow-mediated dilation (FMD)], circulating IL-6, and circulating miR were also measured in young, healthy AA and CA individuals before and after receiving the influenza vaccine. There were no significant racial differences in any parameters at baseline. The vaccine induced increases in IL-6 release (24%, P = 0.02) and ICAM-1 mRNA (40%, P = 0.03), as well as reduced eNOS mRNA (24%, P = 0.04) in AA HUVECs, but not in CA HUVECs (all P > 0.05). Intracellular levels of anti-inflammatory miR-221-3p and miR-222-3p increased specifically in CA HUVECs (72% and 53%, P = 0.04 and P = 0.06), whereas others did not change in either race. HUVEC secretion of several miRs decreased in both races, whereas the release of anti-inflammatory miR-150-5p was decreased only by AA cells (-30%, P = 0.03). In individuals of both races, circulating IL-6 increased approximately twofold 24 h after vaccination (both P < 0.01) and returned to baseline levels by 48 h, whereas FMD remained unchanged. Although macrovascular function was unaffected by acute inflammation in AA and CA individuals, AA endothelial cells exhibited increased susceptibility to acute inflammation and unique changes in related miR.NEW & NOTEWORTHY Used as an acute inflammatory stimulus, the influenza vaccine induced an inflammatory response and decreased eNOS gene expression in endothelial cells derived from African Americans, but not Caucasian Americans. Race-specific changes in intracellular expression and release of specific microRNAs also occurred and may contribute to an exaggerated inflammatory response in African Americans. In vivo, the vaccine caused similar systemic inflammation but had no effect on endothelial function or circulating microRNAs in individuals of either race.

Changes in circulating microRNA and arterial stiffness following high-intensity interval and moderate intensity continuous exercise.

High-intensity interval (HII) exercise elicits distinct vascular responses compared to a matched dose of moderate intensity continuous (MOD) exercise. However, the acute effects of HII compared to MOD exercise on arterial stiffness are incompletely understood. Circulating microRNAs (ci-miRs) may contribute to the vascular effects of exercise. We sought to determine exercise intensity-dependent changes in ci-miR potentially underlying changes in arterial stiffness. Ten young, healthy men underwent well-matched, 30-min HII and MOD exercise bouts. RT-qPCR was used to determine the levels of seven vascular-related ci-miRs in serum obtained immediately before and after exercise. Arterial stiffness measures including carotid to femoral pulse wave velocity (cf-PWV), carotid arterial compliance and ß-stiffness, and augmentation index (AIx and AIx75) were taken before, 10min after and 60min after exercise. Ci-miR-21-5p, 126-3p, 126-5p, 150-5p, 155-5p, and 181b-5p increased after HII exercise (p < .05), while ci-miR-150-5p and 221-3p increased after MOD exercise (p = .03 and 0.056). One hour after HII exercise, cf-PWV trended toward being lower compared to baseline (p = .056) and was significantly lower compared to 60min after MOD exercise (p = .04). Carotid arterial compliance was increased 60min after HII exercise (p = .049) and was greater than 60min after MOD exercise (p = .02). AIx75 increased 10 min after both HII and MOD exercise (p < .05). There were significant correlations between some of the exercise-induced changes in individual ci-miRs and changes in cf-PWV and AIx/AIx75. These results support the hypotheses that arterial stiffness and ci-miRs are altered in an exercise intensity-dependent manner, and ci-miRs may contribute to changes in arterial stiffness.

The effects of moderate and high-intensity exercise on circulating markers of endothelial integrity and activation in young, healthy men.

Endothelial function typically exhibits a hormetic response to exercise. It is unknown whether endothelial damage occurs in response to acute exercise and could be a contributing mechanism. We sought to determine the effects of acute exercise on endothelial-derived circulating factors proposed to reflect endothelial integrity and activation. Young, healthy men (n = 10) underwent 30-min moderate continuous (MOD) and high-intensity interval (HII) cycling exercise bouts. Venous blood samples were taken immediately before and after exercise for quantification of circulating endothelial cells (CECs), circulating angiogenic cells (CACs), apoptotic and activated endothelial microvesicles (EMVs), thrombomodulin (TM), von Willebrand factor (vWF), syndecan-1, and circulating microRNAs (ci-miRs) 126-3p and 126-5p. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery before, 10 min after, and 60 min after exercise. Numbers of CECs and EMVs were unchanged by either exercise bout (P > 0.05). Numbers of all measured CAC subtypes decreased in response to MOD (21%-34%, P < 0.05), whereas only CD31+/34+/45dim/- CACs decreased following HII (21%, P < 0.05). TM and syndecan-1 increased with both exercise intensities (both ~20%, P < 0.05). HII, but not MOD, increased vWF (88%, P < 0.001), ci-miR-126-3p (92%, P = 0.009) and ci-miR-126-5p (110%, P = 0.01). The changes in several circulating factors correlated with changes in FMD following either one or both intensities. Changes in circulating factors do not support the concept of exercise-induced endothelial cell denudation, apoptosis, or activation, though slight disruption of endothelial glycocalyx and membrane integrity may occur. A related loss of mechanotransduction along with mechanisms underlying endothelial activation and ci-miR-126 secretion may relate to changes in endothelial function.NEW & NOTEWORTHY Using circulating endothelial-derived factors, we show that endothelial denudation, apoptosis, and activation do not appear to increase, whereas disrupted endothelial glycocalyx and membrane integrity may occur during both high-intensity interval and moderate intensity cycling. Increases in factors nonspecific to endothelial damage, including von Willebrand factor and microRNA-126, occurred only after high-intensity interval exercise. These results shed light on the hypothesis that disrupted endothelial integrity contributes to the endothelial function response to exercise.