Vascular health of fathers with history of intracytoplasmic sperm injection.

OBJECTIVE: Studies suggest that men who undergo assisted reproductive technologies (ART) may have a higher risk of cardiovascular disease; however, limited data on this matter is available. This observational pilot study aimed to investigate the overall vascular health of fathers with history of intracytoplasmic sperm injection (ICSI) compared to fathers whose partners conceived spontaneously. METHODS: Diet quality, physical activity, sedentary behavior as well as overall vascular function including the assessment of pulse wave analysis, intima-media thickness (cIMT), arterial stiffness of the common carotid artery (CCA) and blood lipids, were evaluated. RESULTS: A total of 34 fathers with history of ICSI and 29 controls (48.49 [46.32 - 57.09] years vs. 47.19 [40.62 - 55.18] years, p = 0.061) were included. After adjusting for age, no significantly increased cardiovascular risk was detected regarding vascular function. CONCLUSIONS: The results suggest an unaltered cardiovascular risk profile in fathers with history of ICSI. In the future, prospective multicenter studies are required to validate these preliminary results.

Factors associated with change in arterial stiffness in patients with rheumatoid arthritis: the JointHeart study.

BACKGROUND: Rheumatoid arthritis (RA) predominantly affects women and is associated with hypertension and arterial stiffness. We explored factors associated with change in arterial stiffness in patients with RA treated with disease-modifying antirheumatic drug (DMARD) therapy. METHODS: Seventy-seven outpatients with RA (age 55 ± 11, 69% women), with indication for treatment with biological or targeted synthetic DMARDs, were included. Pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx) and Disease Activity Score in 28 joints (DAS28) were measured at baseline and after a mean of 22 months of follow-up. RESULTS: At follow-up, 83% used DMARDs and 73% had achieved remission or low disease activity. DAS28 decreased from 3.8 ± 1.3 to 2.8 ± 1.2 (p < 0.001). Mean PWV increased from 7.8 ± 1.6 m/s at baseline to 8.5 ± 1.8 m/s at follow-up (p < 0.001), while AP and AIx were stable. Increase in PWV during follow-up was associated with increase in systolic blood pressure (BP), diabetes, higher DAS28 and body mass index (BMI) at baseline, independent of achieved remission/low disease activity and use of DMARDs at follow-up. In multivariable analyses at follow-up, female sex was associated with higher AP and AIx, but with lower PWV, after adjusting for possible confounders. CONCLUSION: In patients with RA, higher disease activity, BMI and diabetes at baseline, together with increase in office systolic BP were associated with an increase in arterial stiffness during follow-up, despite DMARD therapy. This highlights the need for management of cardiovascular risk factors in addition to reducing the inflammatory load in patients with RA to preserve arterial function.

Rheumatoid arthritis (RA) affects women more often than men and leads to chronic inflammation and faster stiffening of the arteries. In this study, we identified factors that were associated with increase in arterial stiffness during 22 months of follow-up in patients with RA treated with modern antirheumatic medication.This study included 77 patients with RA (69% women), that were in need of change in their disease-modifying antirheumatic medication.We measured arterial stiffness at baseline and repeated it after 22 months of follow-up.At follow-up, arterial stiffness had increased while the disease activity had improved. The rise in arterial stiffness was associated with having diabetes, higher body mass index and higher disease activity at the start of the study and with experiencing an increase in blood pressure during follow-up.This study highlights the need for maintaining a healthy lifestyle and treating cardiovascular risk factors like blood pressure and obesity in patients with RA beyond using modern antirheumatic medication to avoid stiffening of the arteries.

Serum Malondialdehyde-Modified Low-Density Lipoprotein as a Risk Marker for Peripheral Arterial Stiffness in Maintenance Hemodialysis Patients.

Background and Objectives: Peripheral arterial stiffness (PAS), assessed by brachial-ankle pulse wave velocity (baPWV), is an independent biomarker of cardiovascular diseases (CVD) in patients on maintenance hemodialysis (HD). Malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker, has been linked to atherosclerosis and CVD. However, the association between serum MDA-LDL and PAS among HD patients has not been fully elucidated. This study aimed to examine the association of serum MDA-LDL with PAS in HD patients and to identify the optimal cutoff value of serum MDA-LDL for predicting PAS. Materials and Methods: A cross-sectional study was conducted in 100 HD patients. Serum MDA-LDL was quantified using an enzyme-linked immunosorbent assay (ELISA), and baPWV was measured using a volume plethysmographic device. Patients were divided into the PAS group (baPWV > 18.0 m/s) and the non-PAS group (baPWV ≤ 18.0 m/s). The associations of baPWV and other clinical and biochemical parameters with serum MDA-LDL were assessed by multivariable logistic regression analyses. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value of serum MDA-LDL for predicting PAS. Results: In multivariable logistic regression analysis, higher serum MDA-LDL, older age, and higher serum C-reactive protein [odds ratios (ORs) and 95% confidence intervals: 1.014 (1.004-1.025), 1.044 (1.004-1.085) and 3.697 (1.149-11.893)] were significantly associated with PAS. In the ROC curve analysis, the optimal cutoff value of MDA-LDL for predicting PAS was 80.91 mg/dL, with a sensitivity of 79.25% and a specificity of 59.57%. Conclusions: Greater serum MDA-LDL levels, particularly ≥80.91 mg/dL, were independently associated with PAS in HD patients. The findings suggest that oxidative stress plays a crucial role in the pathogenesis of PAS, and targeting MDA-LDL may be a potential therapeutic strategy for reducing cardiovascular risk in HD patients.

Altered Arterial Stiffness, Ventricular-Arterial Coupling and Troponin Levels in Patients with Systemic Lupus Erythematosus.

Introduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease associated with an increased risk of cardiovascular diseases (CVDs), leading to elevated mortality rates among patients. We aimed to evaluate the levels of cardio-ankle vascular index (CAVI), global longitudinal strain (GLS), ventricular-arterial coupling (VAC), and high-sensitivity cardiac troponin I (hsTnI) in SLE patients and to explore their relationship with clinical parameters. Methods: This cross-sectional study enrolled 82 SLE patients without evident cardiac or kidney impairment and 41 age- and sex-matched healthy controls. We comparatively evaluated CAVI, GLS, VAC, and hsTnI between SLE patients and controls, and we assessed their association among SLE patients with disease activity based on the SELENA-SLEDAI Activity Index. Multivariate regression analysis was performed to identify independent predictors of CAVI and hsTnI within the SLE cohort. Results: In comparison to healthy controls, SLE patients presented with significantly higher CAVI, GLS, and hsTnI levels, while VAC was significantly reduced (p < 0.001). Furthermore, SLE patients with active disease (SELENA-SLEDAI ≥ 4) exhibited higher levels of CAVI and troponin than those with inactive disease (p < 0.001). SLEDAI was an independent predictor of CAVI, while VAC and SLEDAI were independent determinants of hsTnI in the SLE cohort. Conclusions: SLE patients displayed abnormal levels of CAVI, VAC, GLS, and troponin compared to healthy individuals. Our findings implicate the potential of those CV novel CVD risk factors to refine screening and therapeutic strategies for this specific population.

Osteocalcin: A Potential Marker of Peripheral Arterial Stiffness in Hypertensive Patients.

Background and Objectives: Brachial-ankle pulse wave velocity (baPWV) is an established independent risk factor for cardiovascular events, cardiovascular mortality, and all-cause mortality. Osteocalcin (OC) is recognized to be associated with vascular function. The present study assessed the correlation between serum OC levels and peripheral arterial stiffness (PAS) measured through baPWV in hypertensive patients. Materials and Methods: Fasting blood samples were collected from 120 hypertensive participants. The serum total OC levels were measured using a commercial enzyme-linked immunosorbent assay kit, whereas the baPWV device was used to detect PAS. The PAS group had left or right baPWV > 18.0 m/s. Results: Among the hypertensive patients, 24 (20.0%) were classified into the PAS group. The PAS group exhibited a significantly older age (p = 0.011), higher prevalence of diabetes (p = 0.010), systolic blood pressure (p = 0.019), levels of serum fasting glucose (p = 0.003), blood urea nitrogen (p = 0.024), creatinine (p = 0.004), C-reactive protein (p = 0.007), OC (p = 0.002), and lower estimated glomerular filtration rate (p = 0.004) than the non-PAS group. Age (odds ratio [OR]: 1.076, 95% CI: 1.004-1.153, p = 0.037) and serum OC level (OR: 1.797, 95% confidence interval (CI): 1.077-3.000, p = 0.025) were independent factors linked to PAS in hypertensive patients in the multivariate logistic regression analysis. Conclusions: Serum OC levels and older age are positively associated with PAS in hypertensive patients.

Abnormal vascular thickness and stiffness in young adults with type 1 diabetes: new insights from cutting-edge ultrasound modalities.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with Type 1 Diabetes (T1D). Early markers of CVD include increased carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), but these existing ultrasound technologies show limited spatial and temporal resolution in young adults. The purpose of this study is to evaluate the utility of high-resolution ultrasound modalities, including high frequency ultrasound CIMT (hfCIMT) and ultrafast ultrasound PWV (ufPWV), in young adults with Type 1 Diabetes. METHODS: This is a prospective single-center observational cohort study including 39 participants with T1D and 25 age and sex matched controls. All participants underwent hfCIMT and ufPWV measurements. hfCIMT and ufPWV measures of T1D were compared with controls and associations with age, sex, BMI, A1c, blood pressure, and lipids were studied. RESULTS: Mean age was 24.1 years old in both groups. T1D had a greater body mass index (27.7 [5.7] vs 23.1 [3.2] kg/m2), LDL Cholesterol, and estimated GFR, and had a mean A1c of 7.4 [1.0] % (57 mmol/mol) and diabetes duration of 16.1 [3.7] years with 56% using insulin pumps. In T1D, hfCIMT was significantly increased as compared to controls (0.435 ± 0.06 mm vs 0.379 ± 0.06 mm respectively, p < 0.01). ufPWV measures were significantly increased in T1D (systolic foot PWV: 5.29 ± 0.23 m/s vs 5.50 ± 0.37 m/s, p < 0.01; dicrotic notch PWV = 7.54 ± 0.46 m/s vs 7.92 ± 0.41 m/s, p < 0.01). Further, there was an impact of A1c-measured glycemia on hfCIMT, but this relationship was not seen with ufPWV. No significant statistical correlations between hfCIMT and ufPWV measures in either T1D or healthy controls were observed. CONCLUSION: Young adults with T1D present with differences in arterial thickness and stiffness when compared with controls. Use of novel high-resolution ultrasound measures describe important relationships between early structural and vascular pathophysiologic changes and are promising tools to evaluate pre-clinical CVD risk in youth with T1D. TRIAL REGISTRATION: ISRCTN91419926.

The role of sirtuins and uncoupling proteins on vascular aging: The Northern Manhattan Study experience.

Aging affects all organs. Arteries, in particular, are among the most affected. Vascular aging (VA) is defined as age-associated changes in function and structure of vessels. Classical VA phenotypes are carotid intima-media thickness (IMT), carotid plaque (CP), and arterial stiffness (STIFF). Individuals have different predisposition to these VA phenotypes and their associated risk of cardiovascular events. Some develop an early vascular aging (EVA), and others are protected and identified as having supernormal vascular aging (SUPERNOVA). The mechanisms leading to these phenotypes are not well understood. In the Northern Manhattan Study (NOMAS), we found genetic variants in the 7 Sirtuins (SIRT) and 5 Uncoupling Proteins (UCP) to be differently associated with risk to developing VA phenotypes. In this article, we review the results of genetic-epidemiology studies to better understand which of the single nucleotide polymorphisms (SNPs) in SIRT and UCP are responsible for both EVA and SUPERNOVA.

Benefits of Puerarin on Metabolic Syndrome and Its Associated Cardiovascular Diseases in Rats Fed a High-Fat/High-Sucrose Diet.

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases (CVDs) that has become a global public health problem. Puerarin (PUE), the principal active compound of Pueraria lobata, has the effects of regulating glucose and lipid metabolism and protecting against cardiovascular damage. This study aimed to investigate whether dietary supplementation with PUE could ameliorate MetS and its associated cardiovascular damage. Rats were randomly divided into three groups: the normal diet group (NC), the high-fat/high-sucrose diet group (HFHS), and the HFHS plus PUE diet group (HFHS-PUE). The results showed that PUE-supplemented rats exhibited enhanced glucose tolerance, improved lipid parameters, and reduced blood pressure compared to those on the HFHS diet alone. Additionally, PUE reversed the HFHS-induced elevations in the atherogenic index (AI) and the activities of serum lactate dehydrogenase (LDH) and creatine kinase (CK). Ultrasonic evaluations indicated that PUE significantly ameliorated cardiac dysfunction and arterial stiffness. Histopathological assessments further confirmed that PUE significantly mitigated cardiac remodeling, arterial remodeling, and neuronal damage in the brain. Moreover, PUE lowered systemic inflammatory indices including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII). In conclusion, dietary supplementation with PUE effectively moderated metabolic disorders, attenuated systemic inflammation, and minimized cardiovascular damage in rats with MetS induced by an HFHS diet. These results provide novel insights into the potential benefits of dietary PUE supplementation for the prevention and management of MetS and its related CVDs.

Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness. CASE PRESENTATION: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels. CONCLUSION: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

Associations of between- and within-day patterns of physical activity accumulation with arterial stiffness and indices of microvascular health-Evidence from The Maastricht study.

While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. Accelerometer-derived (activPAL3) 6- or 7-day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.4% Type 2 diabetes mellitus (T2DM)). Multivariable regression models examined associations between stepping metrics (average step count, and time spent slower and faster paced stepping) with arterial stiffness (measured as carotid-femoral pulse wave velocity (cfPWV)), and several indices of microvascular health (heat-induced skin hyperemia, retinal vessel reactivity and diameter), adjusting for confounders and moderators. PA pattern metrics were added to the regression models to identify associations with vascular health beyond that of stepping metrics. Analyses were stratified by T2DM status if an interaction effect was present. Average step count and time spent faster paced stepping was associated with better vascular health, and the association was stronger in those with compared to those without T2DM. In fully adjusted models a higher step count inter-daily stability was associated with a higher (worse) cfPWV in those without T2DM (std ß = 0.04, p = 0.007) and retinal venular diameter in the whole cohort (std ß = 0.07, p = 0.002). A higher within-day variability in faster paced stepping was associated with a lower (worse) heat-induced skin hyperemia in those with T2DM (std ß = -0.31, p = 0.008). Above and beyond PA volume, the daily and weekly patterns in which PA was accumulated were additionally associated with improved macro- and microvascular health, which may have implications for the prevention of vascular disease.

Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study.

BACKGROUND: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. OBJECTIVES: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. METHODS: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. RESULTS: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0-3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7-12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DISCUSSION: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Effect of Incorporating 1 Avocado per Day Versus Habitual Diet on Vascular Function in Adults With Abdominal Obesity: An Ancillary Study of HAT, a Randomized Controlled Trial.

BACKGROUND: Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. METHODS AND RESULTS: HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. CONCLUSIONS: Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.

Long-term exposure to ambient air pollution and measures of central hemodynamics and arterial stiffness among multiethnic Chicago residents.

OBJECTIVES: To examine whether long-term air pollution exposure is associated with central hemodynamic and brachial artery stiffness parameters. METHODS: We assessed central hemodynamic parameters including central blood pressure, cardiac parameters, systemic vascular compliance and resistance, and brachial artery stiffness measures [including brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR)] using waveform analysis of the arterial pressure signals obtained from a standard cuff sphygmomanometer (DynaPulse2000A, San Diego, CA). The long-term exposures to particles with an aerodynamic diameter < 2.5 µm (PM2.5) and nitrogen dioxide (NO2) for the 3-year periods prior to enrollment were estimated at residential addresses using fine-scale intra-urban spatiotemporal models. Linear mixed models adjusted for potential confounders were used to examine associations between air pollution exposures and health outcomes. RESULTS: The cross-sectional study included 2,387 Chicago residents (76% African Americans) enrolled in the ChicagO Multiethnic Prevention And Surveillance Study (COMPASS) during 2013-2018 with validated address information, PM2.5 or NO2, key covariates, and hemodynamics measurements. We observed long-term concentrations of PM2.5 and NO2 to be positively associated with central systolic, pulse pressure and BAR, and negatively associated with BAD, and BAC after adjusting for relevant covariates. A 1-µg/m3 increment in preceding 3-year exposures to PM2.5 was associated with 1.8 mmHg higher central systolic (95% CI: 0.98, 4.16), 1.0 mmHg higher central pulse pressure (95% CI: 0.42, 2.87), a 0.56%mmHg lower BAD (95% CI: -0.81, -0.30), and a 0.009 mL/mmHg lower BAC (95% CI: -0.01, -0.01). CONCLUSION: This population-based study provides evidence that long-term exposures to PM2.5 and NO2 is related to central BP and arterial stiffness parameters, especially among African Americans.

Is GFR decline induced by SGLT2 inhibitor of clinical importance?

BACKGROUND: Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether the initial decline of renal function with SGLT2 inhibitor treatment is related to vascular changes in the systemic circulation. METHODS: We measured GFR (mGFR) and estimated GFR (eGFR) in 65 patients with type 2 diabetes (T2D) at baseline and after 12 weeks of treatment randomized either to a combination of empagliflozin and linagliptin (SGLT2 inhibitor based treatment group) (n = 34) or metformin and insulin (non-SGLT2 inhibitor based treatment group) (n = 31). mGFR was measured using the gold standard clearance technique by constant infusion of inulin. In addition to blood pressure (BP), we measured pulse wave velocity (PWV) under standardized conditions reflecting vascular compliance of large arteries, as PWV is considered to be one of the most reliable vascular parameter of cardiovascular (CV) prognosis. RESULTS: Both mGFR and eGFR decreased significantly after initiating treatment, but no correlation was found between change in mGFR and change in eGFR in either treatment group (SGLT2 inhibitor based treatment group: r=-0.148, p = 0.404; non-SGLT2 inhibitor based treatment group: r = 0.138, p = 0.460). Noticeably, change in mGFR correlated with change in PWV (r = 0.476, p = 0.005) in the SGLT2 inhibitor based treatment group only and remained significant after adjustment for the change in systolic BP and the change in heart rate (r = 0.422, p = 0.018). No such correlation was observed between the change in eGFR and the change in PWV in either treatment group. CONCLUSIONS: Our main finding is that after initiating a SGLT2 inhibitor based therapy an exaggerated decline in mGFR was related with improved vascular compliance of large arteries reflecting the pharmacologic effects of SGLT2 inhibitor in the renal and systemic vascular bed. Second, in a single patient with T2D, eGFR may not be an appropriate parameter to assess the true change of renal function after receiving SGLT2 inhibitor based therapy. TRIAL REGISTRATION: clinicaltrials.gov (NCT02752113).

Implications of pulse wave velocity and central pulse pressure in heart failure with reduced ejection fraction.

BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV) and central pulse pressure (PP) are recognised as significant indicators of vascular health and predictors of cardiovascular outcomes. In this study, associations between central hemodynamics and left ventricular (LV) echocardiographic parameters were investigated in subjects with heart failure with reduced ejection fraction (HFrEF), comparing the results to healthy individuals. METHODS AND RESULTS: This cross-sectional prospective controlled study included 50 subjects with HFrEF [mean LV ejection fraction (EF) 26 ± 6.5%] and 30 healthy controls (mean LVEF 65.9 ± 5.3%). Pulse wave analysis (PWA) and carotid-femoral pulse wave velocity (cfPWV) were used to measure central hemodynamics and arterial stiffness. The HFrEF group displayed higher cfPWV (8.2 vs. 7.2 m/s, p = 0.007) and lower central (111.3 vs. 121.7 mmHg, p = 0.001) and peripheral (120.1 vs. 131.5 mmHg, p = 0.002) systolic blood pressure. Central pulse pressure (PP) was comparable between the two groups (37.6 vs. 40.4 mmHg, p = 0.169). In the HFrEF group, cfPWV significantly correlated with left ventricular end-diastolic volume (LVEDV) index (mL/m2) and LVEF, with LVEDV index being a significant independent predictor of cfPWV (R2 = 0.42, p = 0.003). Central PP was significantly associated with heart rate, LVEF and LVEDV index, with the latter being a significant independent predictor of central PP (R2 = 0.41, p < 0.001). These correlations were not observed in healthy controls. CONCLUSIONS: Significant associations between central hemodynamic measures and LV echocardiographic parameters were identified, suggesting the potential to use PWA and cfPWV as possible tools for managing HFrEF.

What is the context?Heart failure with reduced ejection fraction (HFrEF) affects millions of people worldwide.Vascular health plays a significant role in the development and progression of HFrEF.This study investigates two indicators of arterial stiffness­pulse wave velocity (PWV) and central pulse pressure (PP)­and their impact on the functioning of the heart in HFrEF patients compared to healthy individuals.What is new?The study found that higher carotid-femoral PWV and central PP, which typically indicate worse vascular health, were associated with better heart function in HFrEF patients. This paradoxical finding suggests that in the context of HFrEF, traditional markers of vascular health may have different implications.The study included non-invasive methods to evaluate these indicators, offering a potential new additional approach for monitoring and managing HFrEF.What is the impact?We could possibly use non-invasively evaluated PWV and central PP (measures of vascular function) as markers of left ventricular function assessment in HFrEF.

Association between A/G ratio and arterial stiffness among Chinese type 2 diabetics: A cross-sectional study.

BACKGROUND: The android-to-gynoid fat ratio (A/G ratio), an emerging indicator of obesity independent of body mass index (BMI), has yet to be conclusively associated with arterial stiffness in type 2 diabetes mellitus (T2DM). This study aimed to construct a nomogram to estimate arterial stiffness risk in diabetics and explore the interaction effect between A/G ratio and traditional obesity indicators on arterial stiffness. METHODS: 1313 diabetics were divided into 2 groups based on arterial stiffness identified by brachial ankle pulse wave velocity (baPWV), and demographic and clinical features were measured. The LASSO and multivariate logistics regression were used to develop the nomogram. Calibration curve, decision curve analysis (DCA) and receiver operating characteristic (ROC) were applied to assess calibration and clinical usefulness. Interaction effect analysis was performed to quantify the interactive relationship of A/G ratio and obesity indicators on arterial stiffness. RESULTS: 6 independent predictors (age, gender, A/G ratio, SBP, LDL-C and HbA1C) were screened to construct a nomogram prediction model. The calibration curve demonstrated satisfactory agreement between predicted and actual probability, and the nomogram exhibited clinical beneficial at the threshold between 8 % and 95 % indicated by DCA. The area under curve (AUC) was 0.918 and 0.833 for training and external set, respectively. Further investigation revealed A/G ratio and BMI acted positively synergistically towards arterial stiffness, and in BMI-based subgroup analysis, elevated A/G ratio was a significant risk factor for arterial stiffness, especially in normal BMI. CONCLUSIONS: A/G ratio showed a substantial association with arterial stiffness, and the nomogram, incorporating age, gender, A/G ratio, SBP, LDL-C, and HbA1c, exhibited high predictive value. A/G ratio measurement in BMI-normal individuals assisted in identifying cardiovascular diseases early.

Associations between estimated glucose disposal rate and arterial stiffness and mortality among US adults with non-alcoholic fatty liver disease.

Background: The estimated glucose disposal rate (eGDR), an effective indicator of insulin resistance, has been related to acute coronary syndrome, ischemic stroke and heart failure. This study aims to explore the relationship between eGDR and arterial stiffness, all-cause mortality and cardiovascular mortality in patients with non-alcoholic fatty liver disease (NAFLD). Methods: Participants with NAFLD were chosen from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. The main outcomes are arterial stiffness (represented by estimated pulse wave velocity, ePWV), all-cause and cardiovascular mortality. Multiple cox regression models, restricted cubic spline, sensitivity analysis and subgroup analysis were carried out to investigate the correlation between the insulin resistance indicators and mortality and arterial stiffness. Furthermore, receiver operating characteristic curves were used to compare the predictive value of the eGDR with the triglyceride-glucose (TyG) index and the homeostasis model assessment of insulin resistance (HOMA-IR) for all-cause and cardiovascular mortality. Results: In this study, a total of 4,861 participants were included for analysis. After adjusting confounding factors in the multivariate weighted cox regression model, the eGDR was inversely associated with the all-cause mortality (Q4 vs. Q1, HR =0.65 (0.48-0.89, P=0.01) and cardiovascular mortality (Q4 vs. Q1, HR =0.35 (0.19-0.65, P<0.001). Compared with TyG index and HOMA-IR, the eGDR shows excellent predictive value in all-cause mortality (0.588 vs. 0.550 vs. 0.513, P < 0.001) and cardiovascular mortality (0.625 vs. 0.553 vs. 0.537, P < 0.001). In addition, we found a significant negative correlation between eGDR and arterial stiffness (ß=-0.13(-0.14-0.11, P< 0.001). However, TyG index and HOMA-IR showed no significant correlation to arterial stiffness. Conclusions: Low eGDR (an indicator of insulin resistance) levels are related to an increased risk of arterial stiffness and mortality in NAFLD patients in the United States.

Flexural pulse wave velocity in blood vessels.

Arteriosclerosis is a major risk factor for cardiovascular disease and results in arterial vessel stiffening. Velocity estimation of the pulse wave sent by the heart and propagating into the arteries is a widely accepted biomarker. This symmetrical pulse wave propagates at a speed which is related to the Young's modulus through the Moens Korteweg (MK) equation. Recently, an antisymmetric flexural wave has been observed in vivo. Unlike the symmetrical wave, it is highly dispersive. This property offers promising applications for monitoring arterial stiffness and early detection of atheromatous plaque. However, as far as it is known, no equivalent of the MK equation exists for flexural pulse waves. To bridge this gap, a beam based theory was developed, and approximate analytical solutions were reached. An experiment in soft polymer artery phantoms was built to observe the dispersion of flexural waves. A good agreement was found between the analytical expression derived from beam theory and experiments. Moreover, numerical simulations validated wave speed dependence on the elastic and geometric parameters at low frequencies. Clinical applications, such as arterial age estimation and arterial pressure measurement, are foreseen.

Determinants of hand pulse wave velocity and hand pulse transit time in healthy adults.

Arterial pulse wave velocity (PWV) is recognized as a convenient method to assess peripheral vascular stiffness. This study explored the clinical characteristics of hand PWV (hPWV) and hand pulse transit time (hPTT) in healthy adults (sixty males = 42.4 ± 13.9 yrs; sixty-four females = 42.8 ± 13.9 yrs) voluntarily participated in this study. The arterial pulse waveform and the anatomical distance from the radial styloid process to the tip of the middle finger of both hands were recorded in the sitting position. The hPWV was calculated as the traversed distance divided by hPTT between those two points. Male subjects showed significantly greater hPWV, systolic blood pressure, and pulse pressure than age-matched female subjects, while the hPTT was not significantly different between genders. Multiple linear regression analysis showed that gender is a common determinant of hPWV and hPTT, and that age and heart rate (HR) were negatively correlated with hPWV and hPTT, respectively. We conclude that male subjects have greater hPWV than female subjects. Ageing is associated with decreased hPWV, while increased HR is associated with a smaller hPTT. The hPWV and hPTT might be used as non-invasive indices to characterise the ageing and arterial stiffness of peripheral blood vessels.