Regular exercise significantly reduces cardiovascular risk and helps prevent primary and secondary cardiac events. However, the mechanisms through which exercise affects cardiovascular health remain unclear. This study investigates the acute effects of high-intensity interval training (HIIT) versus moderate-intensity continuous exercise (MOD) on endothelial function and glycemic control in patients with type 2 diabetes (T2D).

The study aimed to compare the acute effects of a single session of HIIT and MOD on endothelial function, hemodynamic parameters, and blood glucose levels in T2D patients.

This was a randomized controlled trial (RCT).

Conducted at the Laboratory of Cardiopulmonary Rehabilitation.

Fifty-seven sedentary patients with type 2 diabetes (39 women and 18 men) participated in the study.

Participants were randomly assigned to either HIIT (10 sprints of 30 s at 85-100% of maximum heart rate, with 1-min active pauses) or MOD (continuous exercise at 60-70% of maximum heart rate for 30 min). Brachial artery flow-mediated dilation (%FMD) and blood glucose levels were measured before and immediately after the sessions.

HIIT significantly increased %FMD (9.3 ± 5.3% vs 20.05 ± 9.3%, p < 0.01) and reduced glucose levels (189 [106-335] mg/dL vs 149 [70-448] mg/dL, p < 0.01). Although MOD also showed positive responses, HIIT yielded more pronounced improvements in endothelial function.

HIIT is more effective for cardiovascular protection than MOD, although both exercises improve glycemic control in T2D patients. Higher %FMD is associated with better physical capacity and heart rate recovery, indicating a favorable prognosis.

Reduced kidney function is associated with increased risk of cardiovascular disease in addition to kidney disease progression. Kidney disease is considered an inflammatory state, based on elevated levels of C-reactive protein and inflammatory cytokines. A key mediator of cardiovascular and kidney disease progression in the setting of reduced kidney function is systemic and vascular inflammation. However, the exact pathways that link chronic kidney disease (CKD) with inflammation remain incompletely understood. For decades it has been known that factor D, the main activator of the alternative complement pathway, is increased in the plasma of patients with reduced kidney function. Recent biomarker evidence suggests alternative pathway activation in this setting. CKD, therefore, seems to alter the balance of alternative pathway proteins, promoting inflammation and potentially exacerbating complement-mediated diseases and CKD-associated complications. In this manuscript, we review the impact of reduced kidney function on biomarkers of the alternative complement pathway and the implications of alternative pathway activation on cardiovascular disease and kidney disease progression. Importantly, we highlight the need for ongoing research efforts that may lead to opportunities to target the alternative pathway of complement withx the goal of improving kidney and cardiovascular outcomes in persons with reduced kidney function.

High-altitude polycythemia (HAPC) is a pathological state resulting from maladaptation to prolonged high-altitude exposure, posing significant risks to the cardiovascular health of highlanders. However, its influence on hypertension-mediated organ damages (HMODs) in hypertensive individuals remains unclear. We recruited hypertensive patients residing at altitudes above 2500 m for over 3 years. A case-control matching was conducted in a 1:1 ratio between hypertensive patients with and without HAPC, based on gender and age. Echocardiography, carotid artery ultrasound, and brachial flow-mediated dilation (FMD) were measured as HMODs. A total of 88 hypertensive patients were included in the analysis, with 44 with HAPC and 44 without HAPC. Patients with HAPC showed significantly higher hemoglobin (HGB) levels (217.82 ± 17.34 vs. 160.16 ± 13.25, P<0.001), a larger left atrium (LA) diameter (35.36 ± 4.25 vs. 33.09 ± 3.55, P = 0.008), and a higher proportion of impaired FMD (95.45% vs. 79.55%, P = 0.049) compared to those without HAPC. No significant differences were found between the two groups in diastolic function parameters, left ventricular mass index (LVMI), relative wall thickness (RWT), or intima-media thickness (IMT). After adjusting for age, gender, and other confounding factors, HGB remained significantly associated with LA diameter (β = 0.034, P = 0.023) and impaired FMD (OR = 1.034, 95% CI 1.001-1.069). After matching for age and gender, hypertensive patients with HAPC exhibited a significantly larger LA diameter and a higher prevalence of impaired FMD compared to those without HAPC. Additionally, HGB was identified as an independent risk factor for both increased LA diameter and impaired FMD in hypertensive patients with HAPC.

The menopausal transition is associated with increased risk for cardiovascular disease (CVD). Hot flashes (HF), a cardinal symptom of menopause, have been associated with increased CVD risk, particularly in perimenopausal women. Flow-mediated dilation (FMD) is an indicator of endothelial function and a subclinical CVD risk factor. Lower FMD has been associated with more HF. As moderate to vigorous physical activity (MVPA) is recognized to reduce CVD risk, our goal was to determine whether higher levels of MVPA change the relationship between HF and FMD in perimenopausal women. Healthy perimenopausal women had HF measured objectively using sternal skin conductance for 24 h. MVPA was determined using 7 days of actigraphy. Endothelial function was measured via brachial artery FMD on the non-dominant arm. Pearson correlations and multiple regression analyses were used to evaluate relationships between variables. Simple slopes analysis was performed to understand how MVPA moderates the relationship between HF and FMD. Lower FMD tended to correlate with a higher objective HF rate, and this relationship was stronger for HF measured during waking hours. Controlling for age and BMI, HF and the interaction between HF and MVPA were significant predictors of FMD. Simple slope analysis showed a significant HF effect on FMD with lower (-1SD) MVPA, whereas there was no significant relationship between HF and FMD with higher (+1SD) MVPA. These results suggest that MVPA moderates the relationship between FMD and objective HFs in perimenopausal women.

Although affecting both sexes, loss of sex hormones and consequently increased risk for cardiovascular disease (CVD) render particular features to vascular aging in females. More importantly, although the female's vasculature is more sensitive to CVD risk factors, CVD is often underdiagnosed in women. In the present study, we investigated vascular function in the arm and leg skeletal muscle microvasculature and conduit artery in young and older females. We also applied a mixed-effect regression analysis to examine the relationship between vascular function and CVD risk factors in women. We showed that the detrimental effects of age in conduit artery vascular function, as assessed by flow-mediated dilation (%FMD), were more evident in the lower limb (older, 2.6 ± 0.5 vs. young, 7.2 ± 0.9%; P = 0.0116) compared with the upper limb (older, 5.3 ± 0.5 vs. young, 7.3 ± 0.4%; P = 0.175). In addition, we demonstrate that CVD risk factors, mainly plasma lipid levels [very low-density lipoprotein cholesterol (VLDL-c): r2 = 0.415, P = 0.007; high-density lipoprotein cholesterol (HDL-c): r2 = 0.313, P = 0.024; triglycerides: r2 = 0.422, P = 0.006] and insulin sensitivity index [homeostasis model assessment of insulin resistance (HOMA-IR): r2 = 0.635, P < 0.001; QUICKI: r2 = 0.792, P < 0.001], were exclusively associated with upper limb skeletal muscle microvascular function in older females. In aggregate, our findings provide novel evidence that impairments in conduit artery function in older females are more pronounced in the lower limb vasculature compared with the upper limb. Also, we demonstrate that older women's upper limb microvasculature function may be more susceptible to the impact of CVD risk factors than lower limb microvasculature function and both limb's conduit arteries.NEW & NOTEWORTHY Even though the vasculature of older females has been suggested to be more sensitive to the detrimental effects of traditional cardiovascular risk factors, cardiovascular disease in women is often underdiagnosed. We show that aging-associated vascular dysfunction is more evident in the lower limb conduit arteries compared with the upper limb in older women. More importantly, we demonstrate that traditional cardiovascular risk factors were exclusively associated with upper limb skeletal muscle microvascular function in older females.

Maintaining good vascular health is a major component in healthy ageing as it reduces the risk of cardiovascular diseases. Endothelial dysfunction, in particular, is a key mechanism in the development of major cardiovascular diseases including hypertension, atherosclerosis and diabetes. Recently, endothelial senescence has emerged as a pivotal early event in age-related endothelial dysfunction. Endothelial function is characterized by an imbalance between the endothelial formation of vasoprotective mechanisms, including the formation of nitric oxide (NO) and endothelium-dependent hyperpolarization responses, and an increased level of oxidative stress involving several pro-oxidant enzymes such as NADPH oxidases and, often also, the appearance of cyclooxygenase-derived vasoconstrictors. Pre-clinical studies have indicated that natural products, in particular several polyphenol-rich foods, can trigger activating pathways in endothelial cells promoting an increased formation of NO and endothelium-dependent hyperpolarization. In addition, some can even exert beneficial effects on endothelial senescence. Moreover, some of these products have been associated with the prevention and/or improvement of established endothelial dysfunction in several experimental models of cardiovascular diseases and in humans with cardiovascular diseases. Therefore, intake of certain natural products, such as dietary and plant-derived polyphenol-rich products, appears to be an attractive approach for a healthy vascular system in ageing.

Endothelial dysfunction is a pivotal early event in the development of major cardiovascular diseases including hypertension, atherosclerosis, diabetes, and aging. The alteration of the endothelial function is often triggered by an imbalance between the endothelial formation of vasoprotective factors, including nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH), and vasocontracting factors, such as arachidonic acid-derived mediators generated by cyclooxygenases, and an increased level of oxidative stress. Recently, endothelial senescence was reported to be an early trigger of endothelial dysfunction. Preclinical studies indicate that polyphenol-rich food, including anthocyanin-rich products, can activate pathways promoting an increased formation of vasoprotective factors and can prevent the induction of endothelial dysfunction in endothelial cells and isolated blood vessels. Similarly, intake of anthocyanin-rich products has been associated with the prevention and/or the improvement of an endothelial dysfunction in several experimental models of cardiovascular diseases, including physiological aging. Moreover, clinical data indicate that polyphenol-rich and anthocyanin-rich products can improve endothelial function and vascular health in humans with cardiovascular diseases. The present review will discuss both experimental and clinical evidence indicating that several polyphenol-rich foods and natural products, and especially anthocyanin-rich products, can promote endothelial and vascular health, as well as the underlying mechanisms.

Despite recent advances in treatment options, stroke remains a highly prevalent and devastating condition with significant socioeconomic impact. Recanalization therapies, including intravenous thrombolysis and endovascular treatments, have revolutionized stroke management and prognosis, providing a promising framework for exploring new therapeutic strategies. Endothelial dysfunction plays a critical role in the pathophysiology, progression, and prognosis of stroke. This review aims to synthesize the current evidence regarding the involvement of the nitric oxide (NO)/endothelium pathway in ischemic stroke, with a particular focus on aging, response to recanalization therapies, and therapeutic approaches. While significant progress has been made in recent years in understanding the relationship between endothelial dysfunction and stroke, many uncertainties persist, and although treatments targeting this pathway are promising, they have yet to demonstrate clear clinical benefits.

Adverse changes in the gut microbiome with aging are an emerging mediator of arterial dysfunction, which contributes to cardiovascular disease (CVD) development. We investigated the therapeutic potential of enhancing the bioavailability of gut-derived short-chain fatty acids (SCFAs; produced from dietary fiber) for improving age-related arterial dysfunction. We performed gut microbial whole-genome sequencing in young (3 months) versus old (24 months) male C57BL/6N mice to explore changes in bacterial taxonomic abundance and functional pathways with aging and relations to arterial function. We then supplemented young and old mice with the SCFA acetate in drinking water versus controls and versus a high-fiber diet for 8-10 weeks to test the effects of these interventions on vascular function and explore potential mechanisms. Of the various differences in the gut microbiomes of old mice, lower SCFA-producing capacity (taxonomic abundance and functional pathways) stood out as a key feature related to worse arterial function after adjusting for age. Acetate supplementation and a high-fiber diet reversed ~30% of the age-related increase in aortic pulse wave velocity (stiffness) and fully restored carotid artery endothelium-dependent dilation (endothelial function) to young levels. Acetate and a high-fiber diet reduced age-related increases in systemic inflammation. We also found that improvements in endothelial function were likely mediated by suppressed early growth response-1 signaling using innovative siRNA-based knockdown in isolated arteries. There were no effects of the interventions in young mice. Acetate supplementation was comparably effective for ameliorating arterial dysfunction with aging as a high-fiber diet and thus shows promise for reducing CVD risk in older adults.

In assessing the effects of smoking cessation on endothelial function, low-flow-mediated constriction (L-FMC) may provide complementary information to flow-mediated dilation (FMD). However, the value of flow-mediated total dilation (FMTD), an index that incorporates L-FMC into FMD, remains underreported. We aimed to evaluate the effect of smoking cessation on endothelial function, as assessed by FMD and FMTD, and clarify its associated clinical factors.

We enrolled 118 consecutive current smokers without previous coronary artery disease (72.9% were men; age: 59 ± 11 years) who underwent smoking cessation treatment. The clinical variables %FMD, %L-FMC, and %FMTD were examined before and 20 weeks after treatment initiation. A multivariate linear regression model was used to investigate the effects of smoking cessation on %FMD and %FMTD and the interaction between smoking cessation and baseline clinical variables.

After 20 weeks, 85 smokers (69.4% were men; age: 59 ± 12 years) ceased smoking (abstainers), whereas 33 smokers (81.8% were men; age: 58 ± 11 years) did not (continued smokers). The estimated group differences (abstainers - continued smokers) in changes in the %FMD and %FMTD were 0.77% (95% confidence interval [CI], -0.22-1.77%; p = 0.129) and 1.17% (95% CI, 0.16-2.18%; p = 0.024), respectively. Smoking cessation-associated improvement in %FMTD was greater in women than in men (5.41% [95% CI, 3.15-7.67%] versus 0.24% [95% CI, -0.81-1.28%]; p-value for interaction, < 0.001). Additionally, a greater %FMTD improvement was observed in patients who smoked fewer cigarettes per day (p-value for interaction, 0.042) and those who had a smaller resting baseline lumen diameter (Dbase) (p-value for interaction, 0.023).

Smoking cessation was associated with an improvement in %FMTD. Sex, cigarettes smoked per day, and Dbase significantly affected this improvement. The FMTD may help in risk stratification after smoking cessation.

Primary hyperparathyroidism (pHPT) afflicts our aging population with an incidence approaching 50 per 100 000 patient-years at a female:male ratio of ~3:1. Decisions surrounding surgical management are currently driven by age, hypercalcemia severity, presence of osteoporosis, renal insufficiency, or hypercalciuria with or without nephrolithiasis. Cardiovascular (CV) disease (CVD) is not systematically considered. This is notable since the parathyroid hormone (PTH) 1 receptor (PTH1R) is biologically active in the vasculature, and adjusted CV mortality risk is increased almost threefold in individuals with pHPT who do not meet contemporary recommendations for surgical cure. We provide an overview of epidemiology, pharmacology, and physiology that highlights the need to: (i) identify biomarkers that establish a healthy 'set point' for CV PTH1R signaling tone; (ii) better understand the pharmacokinetic-pharmacodynamic (PK-PD) relationships of PTH1R ligands in CV homeostasis; and (iii) incorporate CVD risk assessment into the management of hyperparathyroidism.

Declines in physiological function with aging are strongly linked to age-related diseases. Lifelong voluntary aerobic exercise (LVAE) preserves physiological function with aging, possibly by increasing cellular quality control processes, but the circulating molecular transducers mediating these processes are incompletely understood. The plasma metabolome may predict biological aging and is impacted by a single bout of aerobic exercise. Here, we conducted an ancillary analysis using plasma samples, and physiological function data, from previously reported studies of LVAE in male C57BL/6N mice randomized to LVAE (wheel running) or sedentary (SED) (n = 8-9/group) to determine if LVAE alters the plasma metabolome and whether these changes correlated with preservation of physiological function with LVAE. Physical function (grip strength, coordination, and endurance) was assessed at 3 and 18 months of age; vascular endothelial function and the plasma metabolome were assessed at 19 months. Physical function was preserved (%decline; mean ± SEM) with LVAE vs SED (all p < 0.05)-grip strength, 0.4 ± 1.7% vs 12 ± 4.0%; coordination, 10 ± 4% vs 73 ± 10%; endurance, 1 ± 15% vs 61 ± 5%. Vascular endothelial function with LVAE (88.2 ± 2.0%) was higher than SED (79.1 ± 2.5%; p = 0.03) and similar to the young controls (91.4 ± 2.9%). Fifteen metabolites were different with LVAE compared to SED (FDR < 0.05) and correlated with the preservation of physiological function. Plasma spermidine, a polyamine that increases cellular quality control (e.g., autophagy), correlated with all assessed physiological indices. Autophagy (LC3A/B abundance) was higher in LVAE skeletal muscle compared to SED (p < 0.01) and inversely correlated with plasma spermidine (r =  - 0.5297; p = 0.054). These findings provide novel insight into the circulating molecular transducers by which LVAE may preserve physiological function with aging.

Sickle cell disease (SCD) arises from beta-globin gene mutations, with global estimates indicating around 500 000 affected neonates in 2021. In the United States, it is considered rare, impacting fewer than 200 000 individuals. The key pathogenic flaw lies in mutant haemoglobin S, prone to polymerization under low oxygen conditions, causing erythrocytes to adopt a sickled shape. This leads to complications like vascular occlusion, haemolytic anaemia, inflammation and organ damage. Beyond erythrocyte abnormalities however, there is a body of literature highlighting the hypercoagulable state that is likely a contributor to many of the complications we see in SCD. The persistent activation of the coagulation cascade results in thromboembolic events, notably venous thromboembolism (VTE) which is independently associated with increased mortality in both adults and children with SCD. While the increased risk of VTE in the SCD population seems well established, there is a lack of guidelines for thromboprophylaxis in this population. This Wider Perspective will describe the hypercoagulable state and increased thrombosis risk in the SCD population, as well as advocate for the development of evidence-based guidelines to aid in the prevention of VTE in SCD.

Aging leads to vascular endothelial dysfunction and muscle impairment. While resistance exercise improves muscular function, its acute effects on vascular function vary in the literature, with some studies reporting detrimental effects. These findings indicate the need for exercises that optimize muscle function without compromising vascular function. Reformer Pilates (RP) is a low-impact exercise involving an adjustable sliding platform. However, the acute effects of RP on vascular function among older adults remain unknown. Therefore, this study aimed to investigate the acute effects of RP on vascular function in older adults.

Overall, 17 participants (age: 65 ± 2.76 years, body mass index: 23.42 ± 3.68 kg/m2) were examined and assigned to control and RP conditions under a randomized crossover design. The RP condition involved a 3.5-5 omnibus perceived exertion scale with 19 exercise postures for 60 min. Brachial artery flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), and blood pressure were measured at baseline and 0, 10, 30, and 60 min after exercise.

RP significantly improved FMD at all time points compared with that at baseline (p < 0.05). baPWV increased at 0 min post-RP but returned to baseline levels at other time points. Additionally, RP showed improved FMD at 0, 10, and 30 min compared with that in the control condition (p < 0.05). However, no significant differences were observed in blood pressure or mean arterial pressure in either condition.

RP enhanced FMD and regulated blood pressure for approximately 60 min post-exercise, suggesting its suitability for older adults to enhance vascular function and control blood pressure during exercise. Nonetheless, longitudinal resistance training intervention studies are needed to validate these findings.

Endothelial dysfunction develops with age and may precede cardiovascular disease. Animal data suggest that T-type calcium channels play an important role in endothelial function, but data from humans are lacking. This study included 15 healthy, sedentary, elderly males for a double blinded, randomized controlled trial. For 8 weeks, they were given 40 mg/day of either efonidipine (L- and T-type calcium channel blocker (CCB)) or nifedipine (L-type CCB). Vascular function was evaluated by graded femoral arterial infusions of acetylcholine (ACh; endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator) both with and without co-infusion of N-acetylcysteine (NAC; antioxidant). We measured leg blood flow and mean arterial pressure and calculated leg vascular conductance to evaluate the leg vascular responses. Despite no significant change in blood pressure in either group, we observed higher leg blood flow responses (Δ 0.43 ± 0.45 l/min, P = 0.006) and leg vascular conductance (Δ 5.38 ± 5.67 ml/min/mmHg, P = 0.005) to intra-arterial ACh after efonidipine, whereas there was no change in the nifedipine group, and no differences between groups. We found no upregulation of endothelial nitric oxide synthase in vastus lateralis muscle biopsies within or between groups. Smooth muscle cell responsiveness was unaltered by efonidipine or nifedipine. Intravenous co-infusion of NAC did not affect endothelium-dependent vasodilatation in either of the CCB groups. These results suggest that 8 weeks' inhibition of T- and L-type calcium channels augments endothelium-dependent vasodilatory function in healthy elderly males. Further studies are required to elucidate if T-type calcium channel inhibition can counteract endothelial dysfunction.

Trauma exposure, whether experienced during childhood or adulthood, is prevalent among women. While experiences of trauma are well known to impact mental health, emerging research also links them to women's physical health. The Study of Women's Health Across the Nation (SWAN) and the MsHeart/MsBrain studies, two separate studies devoted to studying midlife women's health, have contributed importantly to the understanding of the implications of trauma to women's health at midlife and beyond. Specifically, findings from these studies have revealed that both childhood and adult trauma exposure are associated with poorer cardiovascular and cerebrovascular health in women, including greater subclinical cardiovascular disease, indicators of cerebral small vessel disease, and increased risk for clinical cardiovascular disease events. When considering trauma types, findings have pointed to the particular importance of sexual and interpersonal violence, such as childhood sexual abuse, intimate-partner violence, sexual harassment, and sexual assault to women's vasculatures. Further, using a range of measures of menopausal vasomotor symptoms, the SWAN and the MsHeart/MsBrain studies have also shown that women with greater trauma exposure have more objectively assessed and self-reported vasomotor symptoms. Finally, although links between trauma exposure and health are not typically explained by post-traumatic stress disorder, work also points to the additional importance of post-traumatic stress disorder to women's cardiovascular and brain health. Collectively, these studies have underscored the importance of trauma to the occurrence of menopausal symptoms, to cardiovascular health, and to women's brain health at midlife and beyond. Future directions and implications for prevention and intervention are discussed.

The arterial system is integral to the proper function of all other organs and tissues. Arterial function is impaired with aging, and arterial dysfunction contributes to the development of numerous age-related diseases, including cardiovascular diseases. The gut microbiome has emerged as an important regulator of both normal host physiological function and impairments in function with aging. The purpose of this review is to summarize more recently published literature demonstrating the role of the gut microbiome in supporting normal arterial development and function and in modulating arterial dysfunction with aging in the absence of overt disease. The gut microbiome can be altered due to a variety of exposures, including physiological aging processes. We explore mechanisms by which the gut microbiome may contribute to age-related arterial dysfunction, with a focus on changes in various gut microbiome-related compounds in circulation. In addition, we discuss how modulating circulating levels of these compounds may be a viable therapeutic approach for improving artery function with aging. Finally, we identify and discuss various experimental considerations and research gaps/areas of future research.

Atherosclerotic changes can be attributed to early endothelial damage in individuals with hypertension. We aimed to explore the relationship between endothelial dysfunction and hypertension in newly diagnosed children without end-organ damage, considering carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), and functional capillaroscopy parameters. We also analyzed the differences between dipper and non-dipper patients.

In this cross-sectional study, 20 patients diagnosed with essential hypertension with no target organ damage, and 20 age and sex-matched healthy volunteers were enrolled. The patient group comprised newly diagnosed individuals not receiving antihypertensive treatment. Hypertensive patients were divided into two groups (dipper and non-dipper patients). The measurements of CIMT, brachial FMD, and functional capillaroscopy were performed before starting treatment.

Among the patients, 11 were boys, and 9 were girls, with a median age of 16.0 (2.13) years. Of 20 hypertensive patients, 10 were dipper and 10 were non-dipper. Significant differences were observed between the hypertensive patients and controls in terms of CIMT (p = 0.04), brachial artery FMD (p = 0.02), and functional capillary density (p < 0.001). Hypertensive patients exhibited increased CIMT, reduced brachial artery FMD, and lower capillary density. However, there were no differences between dippers and non-dippers regarding age, sex, height SDS, weight SDS, CIMT SDS, brachial artery FMD, and capillary density.

Understanding the vascular consequences associated with essential hypertension emphasizes the importance of early detection and management of hypertension. Herein, we have effectively highlighted significant endothelial changes through the analysis of three parameters in newly diagnosed children without apparent target organ damage.

To investigate the short-term efficacy of enhanced external counterpulsation (EECP) on chronic insomnia.

This is a pilot randomized, participant-blind, and sham-controlled study. Forty-six participants with chronic insomnia were randomly assigned in a 1:1 ratio to receive EECP or sham EECP intervention (total of 35 sessions with 45 min each). The primary outcome was Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes included sleep diary, Hospital Anxiety and Depression Scale (HADS), Short-Form Health Survey (SF12), flow mediated dilation (FMD), serum biomarkers of melatonin, cortisol, interleukin-6, and high sensitivity C-reactive protein. Outcomes were assessed after treatment and at 3-month follow-up.

The PSQI was significantly decreased in both EECP and sham groups after 35-session intervention (13.74 to 6.96 in EECP and 13.04 to 9.48 in sham), and EECP decreased PSQI more than sham EECP (p = 0.009). PSQI in two groups kept improved at 3-month follow-up. After treatment, the total sleep time, sleep efficiency, FMD value and SF12 mental component of EECP group were significantly improved, and group differences were found for these outcomes. At follow-up, total sleep time, sleep efficiency and SF12 mental component of EECP group remained improved, and group difference for SF12 mental component was found. Post-treatment and follow-up HADS-A significantly decreased in both groups, with no differences between groups. Post-treatment serum biomarkers showed no differences within and between groups.

Lack of objective sleep measurement.

EECP could improve sleep quality and mental quality of life in chronic insomnia and the therapeutic effect maintained for 3 months.

Despite accumulating evidence on the potential of glucose-lowering agents (GLAs) to prevent cardiovascular events, the comparative effects of GLAs on vascular function remain unclear. This study utilized validated indicators such as flow-mediated dilation (FMD; positive value favors) and pulse wave velocity (PWV; negative value favors) to uncover the comparative effects of GLAs on vascular function.

Randomized controlled trials (RCTs) comparing the effects of GLAs on FMD or PWV with placebo or other GLAs in patients with type 2 diabetes (T2DM) were searched through PubMed and Embase. The frequentist method of network meta-analysis (NMA) was conducted using a random effects model, and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated.

The NMA included 38 RCTs with 2,065 patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose cotransporter-2 inhibitors (SGLT-2Is) had significantly more positive effects on FMD improvement and PWV reduction than placebo. Thiazolidinedione (TZD) treatment resulted in significantly improved FMD compared to other GLAs as well as placebo (SMD: 1.14; 95% CI: 0.84 to 1.43). Both pioglitazone and rosiglitazone were discovered to have considerably more favorable effects on improving FMD and reducing PWV compared to placebo and other GLAs, as a result of the analysis incorporating each drug in the TZD class. The sensitivity analysis results corroborated the main findings.

This NMA showed more favorable effects of GLP-1RAs and SGLT-2Is than placebo in improving both arterial stiffness and endothelial function in patients with T2DM. In addition, TZDs showed superior effects in improving endothelial function as compared with the other GLAs and placebo.

Vascular insulin resistance is commonly observed in obesity and diabetes; yet, insulin action across the vascular tree and the relationship between insulin responses at different vascular locations remains incompletely defined.

To elucidate the impact of elevated free fatty acids (FFAs) on insulin action across the arterial tree and define the relationship among insulin actions in the different arterial segments.

This randomized crossover study assigned healthy lean adults to 2 separate admissions with euglycemic insulin clamp superimposed for the final 120 minutes of 5-hour lipid or matched-volume saline infusion. Vascular measures including peripheral and central arterial blood pressure, brachial artery flow-mediated dilation (FMD), carotid femoral pulse wave velocity (cfPWV), augmentation index (AIx), pulse wave separation analysis, subendocardial viability ratio (SEVR), and skeletal and cardiac muscle microvascular perfusion were determined before and after insulin clamp. Insulin-mediated whole body glucose disposal was calculated.

Insulin enhanced FMD, AIx, reflection magnitude, and cardiac and skeletal muscle microvascular perfusion. Elevation of plasma FFA concentrations to the levels seen in the postabsorptive state in people with insulin resistance suppressed SEVR, blunted insulin-induced increases in FMD and cardiac and skeletal muscle microvascular blood volume, and lowered insulin's ability to reduce AIx and reflection magnitude. In multivariate regression, insulin-mediated muscle microvascular perfusion was independently associated with insulin-mediated FMD and cfPWV.

Clinically relevant elevation of plasma FFA concentrations induces pan-arterial insulin resistance, the vascular insulin resistance outcomes are interconnected, and insulin-mediated muscle microvascular perfusion associates with cardiovascular disease predictors. Our data provide biologic plausibility whereby a causative relationship between FFAs and cardiovascular disease could exist, and suggest that further attention to interventions that block FFA-mediated vascular insulin resistance may be warranted.

Psoriasis is an immune-mediated inflammatory disease associated with an increased risk of cardiovascular disease (CVD). The risk of CVD increases with the severity of psoriasis, and exposure to systemic inflammation may partly explain the increased risk of CVD in these patients. This raises the question of whether anti-psoriatic treatment, in addition to treating the skin lesions, also lowers the risk of developing CVD. Different types of studies have examined the impact of systemic anti-psoriatic treatments on the risk of CVD in patients with psoriasis and epidemiological observational studies with, e.g., myocardial infarction and stroke as outcomes, and clinical studies investigating circulating inflammatory biomarkers in the blood indicate that anti-psoriatic therapy has a protective effect; however, no randomized controlled trial (RCT) has examined the impact of systemic anti-psoriatic treatment on future hard cardiovascular endpoints. This narrative review provides an overview of the clinical cardiovascular imaging studies examining the effect of systemic anti-psoriatic treatment on the risk of subclinical CVD in patients with psoriasis. We found a total of 24 clinical imaging studies, where 16 of these were observational cohort studies and eight were RCTs. The observational studies suggest an improvement in the risk of subclinical CVD based on different cardiovascular imaging biomarkers; however, the RCTs showed inconsistent results and mainly included vascular inflammation as the outcome. Future RCTs including other imaging biomarkers as surrogates for subclinical CVD, with longer follow-up and with hard cardiovascular endpoints are warranted to address whether systemic anti-psoriatic treatments reduce the risk of CVD.

Patients with systemic lupus erythematosus (SLE) have increased risk of premature atherosclerosis but the exact mechanisms remains unclear. Flow-mediated dilatation (FMD) is an established non-invasive assessment of vascular endothelial function. Lipoprotein subfractions may be better predictors of FMD than conventional cholesterol measurements. We tested the hypothesis that lipoprotein subfractions are independently associated with FMD.

Forty-one consecutive adult patients with SLE without known cardiovascular risk factors or disease were recruited in this cross-sectional study. Endothelial function and early atherosclerosis were assessed by brachial FMD and common carotid artery (CCA) intima-media thickness (IMT). High-density lipoprotein (HDL)/low-density lipoprotein (LDL) subfractions were measured. Machine learning models were also constructed to predict FMD and CCA IMT.

Median FMD was 4.48% (IQR 5.00%) while median IMT was 0.54 mm (IQR 0.12 mm). Univariate analysis showed lower LDL1 (r=-0.313, p<0.05) and higher HDL2 subfractions (r=0.313, p<0.05) were significantly associated with higher log-transformed FMD. In a multiple linear regression model, HDL2 (β=0.024, SE=0.012, p<0.05) remained an independent predictor of higher FMD after adjusting for age, body mass index, LDL1 and systolic blood pressure. The machine learning model included parameters such as HDL2 (positive association), prednisolone dose, LDL cholesterol and LDL1 for prediction of FMD (r=0.433, p<0.01). Age, LDL cholesterol and systolic blood pressure were independently associated with higher CCA IMT after adjusting for body mass index and HDL2.

HDL 2, a large HDL particle, was independently associated with greater FMD and may be a biomarker of vascular health in SLE.

The effect of increased vitamin D levels on vascular function in patients with chronic kidney disease (CKD) is controversial. This meta-analysis aimed to assess the effect of regulated vitamin D increase on vascular markers in patients with CKD.

We searched PubMed, Web of Science, Embase and ClinicalTrials.gov from database inception up until July 21, 2023. We included randomized controlled trials assessing the effects of using vitamin D and its analogues on vascular function in patients with CKD. Fixed-effects and random-effects model analyses were performed using weighted mean difference effects for each trial by heterogeneity (I2) assessment. Primary outcomes encompassed blood flow-mediated dilation (FMD)、pulse wave velocity (PWV) and augmentation index (AIx).

From 1964 records we selected 12 trials, 5 (n = 331) on FMD, 8 (n = 626) on PWV and 4 (n = 393) on AIx. Vitamin D and VDRA supplementation failed to significantly improve FMD (WMD 1.68%; 95% CI -0.18 to 3.53; P = 0.08; I2 = 88%)、PWV (WMD -0.41 m/s; 95%CI -0.95 to 0.13; P = 0.14; I2 = 57%)and AIx (WMD -0.53%; 95%CI -1.69 to 0.63; P = 0.37; I2 = 0%). Subgroup analysis revealed that 2 μg paricalcitol significantly improved FMD (WMD 2.09%; 95%CI 1.28 to 2.90; P < 0.00001); I2 = 0%), as did cholecalciferol (WMD 5.49%; 95% CI 4.35 to 6.63; P < 0.00001).

Supplementation vitamin D and VDRA are associated with improved vascular function as measured by FMD, but not arterial stiffness as measured by PWV and AIx, tentatively suggesting that regulating the increase of vitamin D could not potentially reduce the incidence of cardiovascular disease.

Flow-mediated dilation (FMD) measures vascular endothelial function by evaluating the vasodilatory response of blood vessels to increased blood flow. Nevertheless, the association between FMD and stroke incidence in a general population remains unclear. This study investigated the association between vascular endothelial function and stroke incidence in the general Japanese population.

Based on cohort data from the Tohoku Medical Megabank Community-based Cohort Study, participants aged ≥18 years were recruited from Iwate Prefecture, with the final sample comprising 2952 subjects.

The FMD level was 0.5%-27.1%, with a median of 5.0% (interquartile, 4.2%-11.3%). The mean follow-up period was 5.5 ± 1.8 years (range, 0.6-6.9 years). After dividing the participants into two subgroups according to the median FMD value, a multivariate Cox regression analysis adjusting for gender, age, smoking, alcohol consumption, systolic blood pressure, low-density lipoprotein cholesterol, estimated glomerular filtration rate, N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin T and hemoglobin A1c revealed that a lower FMD value was strongly associated with incidences of total stroke (hazard ratio[HR] = 2.13, 95% confidence interval[CI] = 1.48-3.07, p < 0.001), ischemic stroke (HR = 3.33, 95%CI = 2.00-5.52, p < 0.001), nonlacunar stroke (HR = 2.77, 95%CI = 1.49-5.16, p = 0.001), and lacunar stroke (HR = 5.12, 95%CI = 1.74-16.05, p = 0.003).

This study showed that a low FMD value might reflect vascular endothelial dysfunction and then was associated with ischemic stroke incidence in the general Japanese population, suggesting that FMD can be used as a tool to identify future stroke risk.

Endothelial dysfunction is a key-feature in acute COVID-19. However, follow-up data regarding endothelial dysfunction and injury after COVID-19 infection are lacking. We aimed to investigate the changes in endothelium-dependent vasorelaxation at baseline and four months after hospital discharge in COVID-19 patients.

Twenty COVID-19 patients were compared to 24 healthy controls. Clinical and morphological data were collected after hospital admission for SARS-CoV-2 infection and reactive hyperaemia index (RHI) measurement was performed with a delay between 24 and 48 h after hospital admission and four months after hospital discharge in the outpatient clinics. Blood tests including inflammatory markers and measurement of post-occlusive vasorelaxation by digital peripheral arterial tonometry were performed at both visits.

At baseline, COVID-19 patients exhibited reduced RHI compared to controls (p < 0.001), in line with an endothelial dysfunction. At four months follow-up, there was a 51% increase in the RHI (1.69 ± 0.32 to 2.51 ± 0.91; p < 0.01) in favor of endothelium-dependent vascular relaxation recovery. RHI changes were positively correlated with baseline C-reactive protein (r = 0.68; p = 0.02). Compared to COVID-19 patients with a decrease in RHI, COVID-19 patients with an increase in RHI beyond the day-to-day variability (i.e. >11%) had less severe systemic inflammation at baseline.

Convalescent COVID-19 patients showed a recovery of systemic artery endothelial dysfunction, in particular patients with lower inflammation at baseline. Further studies are needed to decipher the interplay between inflammation and endothelial dysfunction in COVID-19 patients.

Non-obstructive coronary artery disease (CAD) is a disease commonly diagnosed in patients undergoing coronary angiography. However, little is known regarding the long-term clinical impact of multi-vessel non-obstructive CAD. Therefore, the object of this study was to investigate the long-term clinical impact of multi-vessel non-obstructive CAD.

A total of 2083 patients without revascularization history and obstructive CAD were enrolled between January 2010 and December 2015. They were classified into four groups according to number of vessels involved in non-obstructive CAD (25% ≤ luminal stenosis < 70%): zero, one, two, or three diseased vessels (DVs). We monitored the patients for 5 years. The primary outcome was major cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiac death, stroke, and myocardial infarction (MI).

The occurrence of MACCEs increased as the number of non-obstructive DVs increased, and was especially high in patients with three DVs. After adjustment, patients with three DVs still showed significantly poorer clinical outcomes of MACCEs, stroke, and MI compared those with zero DVs.

Multi-vessel non-obstructive CAD, especially in patients with non-obstructive three DVs, is strongly associated with poor long-term clinical outcomes. This finding suggests that more intensive treatment may be required in this subset of patients.

Endothelial dysfunction assessed by impaired brachial flow-mediated dilation (FMD) predicts incident cardiovascular disease (CVD). We have previously shown that clustering of diabetes mellitus, obesity, and metabolic syndrome in young Hispanic patients was associated with subclinical atherosclerosis. This study aimed to assess determinants of impaired FMD response (%FMD), an earlier marker of atherosclerosis, in a population-based sample of asymptomatic Mexican Americans. Cardiometabolic biomarkers and FMD were obtained from 960 Cameron County Hispanic Cohort participants. Gender-specific median values of %FMD were used to categorize participants into those with %FMD below or above the median. The sample was further stratified into those younger and older than 55 years. Survey-weighted logistic regression analyses were conducted to evaluate the effects of cardiometabolic biomarkers on the %FMD groups. The low %FMD group was significantly older, had higher visceral adipose tissue, systolic blood pressure, or plasma glucose, and had metabolic syndrome compared with those in the high %FMD group. Multivariable-adjusted age-stratified logistic regression analyses showed that in older participants, male gender (odds ratio [OR] = 2.4 [1.4 to 4.2]) and having hypertension (OR = 2.3 [1.3 to 4.3]) or prediabetes mellitus (OR = 3.4 [1.5 to 7.5]) remained significantly associated with odds of low %FMD. In younger participants, high low-density lipoprotein (OR = 2.8 [1.6 to 4.9]) or having the metabolic syndrome (OR = 1.9 [1.1 to 3.6]) were significantly associated with odds of low %FMD. In conclusion, we found age-dependent associations between cardiometabolic biomarkers and an FMD response below the gender-specific median in a sample composed of Mexican Americans without previous CVD. Targeting specific risk factors by age may mitigate progression to incident CVD in this high-risk racial disparity group.

Regular Finnish sauna use is associated with a reduced risk of cardiovascular mortality. However, physiological mechanisms underlying this association remain unknown. This study determined if an 8-wk Finnish sauna intervention improves peripheral endothelial function, microvascular function, central arterial stiffness, and blood pressure in adults with coronary artery disease (CAD). Forty-one adults (62 ± 6 yr, 33 men/8 women) with stable CAD were randomized to 8 wk of Finnish sauna use (n = 21, 4 sessions/wk, 20-30 min/session, 79°C, 13% relative humidity) or a control intervention (n = 20, lifestyle maintenance). Brachial artery flow-mediated dilation (FMD), carotid-femoral pulse wave velocity (cf-PWV), total (area under the curve) and peak postocclusion forearm reactive hyperemia, and blood pressure (automated auscultation) were measured before and after the intervention. After the sauna intervention, resting core temperature was lower (-0.27°C [-0.54, -0.01], P = 0.046) and sweat rate during sauna exposure was greater (0.3 L/h [0.1, 0.5], P = 0.003). The change in brachial artery FMD did not differ between interventions (control: 0.07% [-0.99, +1.14] vs. sauna: 0.15% [-0.89, +1.19], interaction P = 0.909). The change in total (P = 0.031) and peak (P = 0.024) reactive hyperemia differed between interventions due to a nonsignificant decrease in response to the sauna intervention and an increase in response to control. The change in cf-PWV (P = 0.816), systolic (P = 0.951), and diastolic (P = 0.292) blood pressure did not differ between interventions. These results demonstrate that four sessions of Finnish sauna bathing per week for 8 wk does not improve markers of vascular health in adults with stable CAD.NEW & NOTEWORTHY This study determined if unsupervised Finnish sauna bathing for 8 wk improves markers of vascular health in adults with coronary artery disease. Finnish sauna bathing reduced resting core temperature and improved sweating capacity, indicative of heat acclimation. Despite evidence of heat acclimation, Finnish sauna bathing did not improve markers of endothelial function, microvascular function, arterial stiffness, or blood pressure.

Here, we assessed the role of cellular senescence and the senescence associated secretory phenotype (SASP) in age-related aortic stiffening and endothelial dysfunction.

We studied young (6-8 mo) and old (27-29 mo) p16-3MR mice, which allows for genetic-based clearance of senescent cells with ganciclovir (GCV). We also treated old C57BL/6N mice with the senolytic ABT-263.

In old mice, GCV reduced aortic stiffness assessed by aortic pulse wave velocity (PWV; 477±10 vs. 382±7 cm/s, P<0.05) to young levels (old-GCV vs. young-vehicle, P=0.35); ABT-263 also reduced aortic PWV in old mice (446±9 to 356±11 cm/s, P<0.05). Aortic adventitial collagen was reduced by GCV (P<0.05) and ABT-263 (P=0.12) in old mice. To show an effect of the circulating SASP, we demonstrated that plasma exposure from Old-vehicle p16-3MR mice, but not from Old-GCV mice, induced aortic stiffening assessed ex vivo (elastic modulus; P<0.05). Plasma proteomics implicated glycolysis in circulating SASP-mediated aortic stiffening. In old p16-3MR mice, GCV increased endothelial function assessed via peak carotid artery endothelium-dependent dilation (EDD; Old-GCV, 94±1% vs. Old-vehicle, 84±2%, P<0.05) to young levels (Old-GCV vs. young-vehicle, P=0.98), and EDD was higher in old C57BL/6N mice treated with ABT-263 vs. vehicle (96±1% vs. 82±3%, P<0.05). Improvements in endothelial function were mediated by increased nitric oxide (NO) bioavailability (P<0.05) and reduced oxidative stress (P<0.05). Circulating SASP factors related to NO signaling were associated with greater NO-mediated EDD following senescent cell clearance.

Cellular senescence and the SASP contribute to vascular aging and senolytics hold promise for improving age-related vascular function.

The world population is aging rapidly, and by some estimates, the number of people older than 60 will double in the next 30 years. With the increase in life expectancy, adverse effects of environmental exposures start playing a more prominent role in human health. Air pollution is now widely considered the most detrimental of all environmental risk factors, with some studies estimating that almost 20% of all deaths globally could be attributed to poor air quality. Cardiovascular diseases are the leading cause of death worldwide and will continue to account for the most significant percentage of non-communicable disease burden. Cardiovascular aging with defined pathomechanisms is a major trigger of cardiovascular disease in old age. Effects of environmental risk factors on cardiovascular aging should be considered in order to increase the health span and reduce the burden of cardiovascular disease in older populations. In this review, we explore the effects of air pollution on cardiovascular aging, from the molecular mechanisms to cardiovascular manifestations of aging and, finally, the age-related cardiovascular outcomes. We also explore the distinction between the effects of air pollution on healthy aging and disease progression. Future efforts should focus on extending the health span rather than the lifespan.

Hypertension is a primary risk factor for cardiovascular disease. Cardiovascular disease is the leading cause of death among adults worldwide. In this review, we focus on two of the most critical public health challenges that contribute to hypertension-obesity and excess dietary sodium from salt (i.e., sodium chloride). While the independent effects of these factors have been studied extensively, the interplay of obesity and excess salt overconsumption is not well understood. Here, we discuss both the independent and combined effects of excess obesity and dietary salt given their contributions to vascular dysfunction, autonomic cardiovascular dysregulation, kidney dysfunction, and insulin resistance. We discuss the role of ultra-processed foods-accounting for nearly 60% of energy intake in America-as a major contributor to both obesity and salt overconsumption. We highlight the influence of obesity on elevated blood pressure in the presence of a high-salt diet (i.e., salt sensitivity). Throughout the review, we highlight critical gaps in knowledge that should be filled to inform us of the prevention, management, treatment, and mitigation strategies for addressing these public health challenges.

An acute exacerbation of COPD (AECOPD) is associated with increased risk of cardiovascular (CV) events. The elevated risk during an AECOPD may be related to changes in vascular function, arterial stiffness, and systemic inflammation; the time course of these measures and their corresponding recovery are poorly understood. Further, physical activity is reduced during an AECOPD, and physical activity may influence the cardiovascular responses to an AECOPD. The purpose of the study was to examine the acute impact of an AECOPD requiring hospitalization on vascular function, arterial stiffness, and systemic inflammation and examine whether physical activity modulates these variables during recovery. Patients hospitalized for an AECOPD were prospectively recruited and compared to control patients with stable COPD. Vascular function, arterial stiffness, and systemic inflammation (CRP, IL-6) were measured at hospital admission, hospital discharge and within 14 days of discharge. Physical activity was electronically tracked daily while in hospital and for 7 days following discharge using a Fitbit. One hundred and twenty-one patients with an AECOPD requiring hospitalization and 33 control patients with stable COPD were enrolled in the study. Vascular function was significantly lower, and systemic inflammation higher at hospital admission in patients with an AECOPD compared to stable COPD. Significant improvements in vascular function and inflammation were observed within 14 days of hospital discharge; however, vascular function remained lower than stable COPD. Physical activity was low at admission and increased following discharge; however, physical activity was unrelated to measures of vascular function or inflammation at any time point. An AECOPD requiring hospitalization is associated with impaired vascular function that persists during recovery. These findings provide a mechanistic link to help explain the enduring increase in CV risk and mortality following a severe AECOPD event.Clinical trial registration: ClinicalTrials.gov #NCT01949727; Registered: 09/20/2013.

Ischemia and reperfusion (IR) damage organs and contribute to many disease states. Few effective treatments exist that attenuate IR injury. The augmentation of nitric oxide (NO) signaling remains a promising therapeutic target for IR injury. NO binds to soluble guanylyl cyclase (sGC) to regulate vasodilation, maintain endothelial barrier integrity, and modulate inflammation through the production of cyclic-GMP in vascular smooth muscle. Pharmacologic sGC stimulators and activators have recently been developed. In preclinical studies, sGC stimulators, which augment the reduced form of sGC, and activators, which activate the oxidized non-NO binding form of sGC, increase vasodilation and decrease cardiac, cerebral, renal, pulmonary, and hepatic injury following IR. These effects may be a result of the improved regulation of perfusion and decreased oxidative injury during IR. sGC stimulators are now used clinically to treat some chronic conditions such as heart failure and pulmonary hypertension. Clinical trials of sGC activators have been terminated secondary to adverse side effects including hypotension. Additional clinical studies to investigate the effects of sGC stimulation and activation during acute conditions, such as IR, are warranted.

Endothelial dysfunction in patients with diabetic nephropathy is caused by nontraditional factors in addition to common risk factors (e.g., hypertension) in people with normal kidney function. These nontraditional factors include factors involved in mineral bone disease in these patients. One of these factors is fibroblast growth factor 23 (FGF-23). We aimed to evaluate the relationship between flow-mediated dilatation (FMD) as a measure of endothelial dysfunction and FGF-23. This was a cross-sectional observational study that was conducted on 100 diabetic patients (Group I: 50 patients with nephropathy; Group II: 50 patients without nephropathy) and 50 healthy volunteers (Group III). Serum levels of intact FGF-23, interleukin-6, intact parathyroid hormone, and 25-hydroxyvitamin D (25-(OH)Vit D); estimated insulin resistance; and FMD were evaluated. FGF-23 was significantly higher in Group I (median: 101 pg/mL) and Group II (median: 101 pg/mL) than in Group III (median: 4 pg/mL) (P <0.001), but FGF-23 was not significantly different between Groups I and II. A significant positive correlation was found between serum levels of FGF-23 and phosphorus in Group I. A significant negative correlation was found between serum levels of FGF-23 and 25-(OH)Vit D in Group II. However, FGF-23 failed to show a significant correlation with FMD in patients with diabetic nephropathy. Our data suggest another factor that rises earlier than FGF-23 in diabetic nephropathy and causes endothelial dysfunction.

Acute exposure to e-cigarette aerosol has been shown to have potentially deleterious effects on the cardiovascular system. However, the cardiovascular effects of habitual e-cigarette use have not been fully elucidated. Therefore, we aimed to assess the association of habitual e-cigarette use with endothelial dysfunction and inflammation - subclinical markers known to be associated with increased cardiovascular risk.

In this cross-sectional study, we analyzed data from 46 participants (23 exclusive e-cigarette users; 23 non-users) enrolled in the VAPORS-Endothelial function study. E-cigarette users had used e-cigarettes for ≥6 consecutive months. Non-users had used e-cigarettes <5 times and had a negative urine cotinine test (<30 ng/mL). Flow-mediated dilation (FMD) and reactive hyperemia index (RHI) were used to assess endothelial dysfunction, and we assayed high-sensitivity C-reactive protein, interleukin-6, fibrinogen, p-selectin, and myeloperoxidase as serum measures of inflammation. We used multivariable linear regression to assess the association of e-cigarette use with the markers of endothelial dysfunction and inflammation.

Of the 46 participants with mean age of 24.3 ± 4.0 years, the majority were males (78%), non-Hispanic (89%), and White (59%). Among non-users, 6 had cotinine levels <10 ng/mL while 17 had levels 10-30 ng/mL. Conversely, among e-cigarette users, the majority (14 of 23) had cotinine ≥500 ng/mL. At baseline, the systolic blood pressure was higher among e-cigarette users than non-users (p=0.011). The mean FMD was slightly lower among e-cigarette users (6.32%) compared to non-users (6.53%). However, in the adjusted analysis, current e-cigarette users did not differ significantly from non-users in their mean FMD (Coefficient=2.05; 95% CI: -2.52-6.63) or RHI (Coefficient= -0.20; 95% CI: -0.88-0.49). Similarly, the levels of inflammatory markers were generally low and did not differ between e-cigarette users and non-users.

Our findings suggest that e-cigarette use may not be significantly associated with endothelial dysfunction and systemic inflammation in relatively young and healthy individuals. Longer term studies with larger sample sizes are needed to validate these findings.

Studies investigating clinical outcomes of patients with or without endothelial disfunction (ED) treated with percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) using second generation drug eluting stents (DES) are lacking.

We prospectively collected data from 109 patients undergoing PCI with second generation DES due to stable CAD between December 2014 and September 2016. ED was evaluated evaluating the flow mediated dilation (FMD) at the brachial artery level and defined by an FMD < 7 %. Primary outcome were major adverse cardiovascular events (MACE), secondary outcomes were target vessel failure (TVR), myocardial infarction (MI) and all-cause death.

Five-year follow-up was available in all patients. Median FMD didn't significantly differ between patients who experienced the outcome and those who didn't [no TVR vs. TVR: p = 0.358; no MI vs. MI: p = 0.157; no death vs. death: p = 0.355; no MACE vs. MACE: p = 0.805]. No association between ED and an increased risk for the primary outcome as well as for the secondary ones was evident [MACE: 17.0 % vs. 14.3 %, HR 0.87 (0.33-2.26), log rank p = 0.780; TVR: 9.4 % vs. 5.4 %, HR 0.53 (0.12-2.24), log rank p = 0.384; MI: 3.7 % vs. 8.9 %, HR 2.46 (0.47-12.76), log rank p = 0.265; death: 7.5 % vs. 3.6 %, HR 0.53 (0.09-2.90), log rank p = 0.458]. These findings were confirmed using a lower threshold of FMD to define ED and at one-year landmark analysis.

ED is not associated with an increased risk of adverse events at long-term follow-up in a contemporary cohort of patients undergoing PCI with second generation DES.