Lower Pulse Pressure Research Articles

CHARACTERISTIC OF RESPONDERS TO RENAL DENERVATION - CROATIAN REAL-LIFE STUDY

Objective: Heterogeneity in response to renal denervation (RDN) is acknowledged phenomena and one of most important tasks in this field is to find reliable predictive biomarker for positive response. Our aim was to analyse characteristics of resistant hypertensive patients who were responders 6 months after RDN. Design and method: Out of 31 truly resistant patients whom secondary forms of hypertension were ruled out and were enrolled into the Croatian Spyral RDN registry, 18 (10 m, 8 w, average age 49.3) were eligible for analyses. Office BP, ABPM, central BP and PWV were measured with Omron M6, Molbilograph and Sphygmocor devices, respectively. Sympathetic/parasympathetic activity was measured with ANX-3.0 ANSAR device. Results: Responders were 6.7 years older, less obese with at basal slightly higher eGFR (88.6 vs. 79.8), uric acid (406.5 vs. 376.4), salt intake (12.6 g/day vs.9.8 g/day) and had significantly higher basal office BP (169.5/99.7 vs. 153.3/96.5) as well as ABPM values. Central aortic systolic BP and Aix were higher in responders (154.5 vs, 147.1; 31.5 vs 27.3) without difference in PWV (10.1 vs. 9.6). Responders had lower values of PP amplification (1.22 vs. 1.33). Significantly higher basal sympathetic activity (LFa/RFa) was determined in responders than in non-responders (6.68 vs. 1.25). Conclusions: Responders were older with higher basal office BP, ABPM but also higher central BP and Aix with lower pulse pressure amplification. They ingested more salt, had higher values of uric acid and importantly had more exaggerated sympathetic activity. Whether some of identified parameters could be considered as a biomarker for positive response in resistant hypertensive patients should be determined in larger cohort of patients.

Systolic, diastolic blood pressure and pulse pressure and risk of stroke in young aged patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background It is well-known that higher blood pressure (BP) is associated with a higher risk of stroke with atrial fibrillation (AF). However, there is limited data about the effect of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) on the risk of ischemic stroke in young and low-risk AF patients Methods Using the Korean Health Insurance Service database, patients who were newly diagnosed with AF between January 2009 and December 2016 and had health screening examination data within 2-year after AF diagnosis were included. Patients aged between 20 and 39 years were finally included in this analysis. During follow-up, incident ischemic stroke was evaluated as a primary outcome. Hazard ratio (HR) and the corresponding 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazard models. Results A total of 15,980 patients were included in this analysis (mean age 32.4±4.8 years, 66.9% of men). Mean CHA2DS2-VASc score was 0.7±0.8 and oral anticoagulation rate was 5.6%. During a median 5.2-year of follow-up, 73 patients had an incident ischemic stroke (incidence rate, 0.9 per 1,000 person-years). After multivariable adjustment, SBP ranging from 140 to 159 mmHg and 160 mmHg or higher were associated with a significantly higher risk of ischemic stroke by 8.4-fold and 11.6-fold compared to SBP under 100 mmHg (Figure). DBP 95mmHg or higher was associated with a higher risk of ischemic stroke by 4.2-fold than DBP under 65 mmHg (Figure). Patients with PP ranging from 50 to 59 mmHg and 60 mmHg or higher showed a significantly higher risk of ischemic stroke than those with PP ranging from 40 to 49 mmHg (HR [95% CI]; 1.81 [1.04-3.18] and 3.15 [1.49-6.64], respectively). Also, lower PP than 30 mmHg was associated with a higher risk of stroke (3.96 [1.36-11.53]). Conclusion Optimal BP control might be crucial to preventing ischemic stroke in these young and low-risk AF patients.

The Associations of Pulse Pressure and Mean Arterial Pressure on Physical Function in Older Americans.

We sought to examine the associations of pulse pressure (PP) and mean arterial pressure (MAP) on physical function in older Americans. Our analytic sample included 10,478 adults aged ≥65 years from the 2006-2016 Health and Retirement Study. Handgrip strength, gait speed, and standing balance were collected using relatively standard protocols. PP and MAP were calculated from blood pressure measurements. Older Americans with any abnormality in PP had 1.15 (95% confidence interval (CI): 1.05-1.25) greater odds for slowness and 1.14 (CI: 1.05-1.24) greater odds for poorer standing balance. Persons with any abnormality in MAP had 0.90 (CI: 0.82-0.98) decreased odds for weakness and 1.10 (CI: 1.01-1.20) greater odds for poorer standing balance. Those with low PP had 1.19 (CI: 1.03-1.36) greater odds for slow gait speed, while persons with low MAP had 1.50 (CI: 1.09-2.05) greater odds for weakness and 1.45 (CI: 1.03-2.04) greater odds for slowness. Older Americans with high PP had 1.13 (CI: 1.03-1.25) greater odds for slowness and 1.21 (CI: 1.10-1.32) greater odds for poorer balance, whereas those with high MAP had 0.87 (CI: 0.80-0.95) decreased odds for weakness. Cardiovascular dysfunction, as observed by PP and MAP, may help to explain some of our findings.

Associations between trajectories of cardiovascular risk factor change and cognitive impairment in Chinese elderly: A nationwide cohort study.

This study aimed to investigate the relationship between long-term trajectories of changes in cardiovascular risk factors (CVRFs) and the risk of cognitive impairment among Chinese adults over 60 years old. Data were obtained from the Chinese Longitudinal Healthy Longevity Survey 2005-2018. Cognitive function was evaluated longitudinally through the Chinese version of the Mini-Mental State Examination (C-MMSE), and cognitive impairment (C-MMSE ≤23) was used as the main outcome variable. The cardiovascular risk factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), and body mass index (BMI), were continuously measured in the follow-up duration. The patterns of trajectories of changes in CVRFs were derived from the latent growth mixture model (LGMM). The Cox regression model was used to evaluate the cognitive impairment hazard ratio (HR) across different CVRF trajectories. A total of 5,164 participants aged ≥60 years with normal cognitive function at baseline were included in the study. After a median follow-up of 8 years, 2,071 participants (40.1%) developed cognitive impairment (C-MMSE ≤ 23). The four-class trajectories of SBP and BMI were obtained by means of LGMM, and the trajectories of DBP, MAP, and PP were grouped into a three-class subgroup. In the final adjusted Cox model, the lowered SBP [adjusted HR (aHR): 1.59; 95% CI: 1.17-2.16], lowered PP (aHR: 2.64; 95% CI: 1.66-4.19), and progressively obese (aHR: 1.28; 95% CI: 1.02-1.62) and stable slim (aHR: 1.13; 95% CI: 1.02-1.25) were associated with the higher risk of cognitive impairment. Low stable DBP (aHR: 0.80; 95% CI: 0.66-0.96) and elevated PP (aHR: 0.76; 95% CI: 0.63-0.92) decreased the risk for cognitive impairment among participants. Lowered SBP, lowered PP, progressive obesity, and stable slim increased the risk for cognitive impairment in the Chinese elderly. Low stable DBP and elevated PP were protective against cognitive impairment, but more DBP lowering and ≥25 mmHg growth in PP contributed to a higher risk of cognitive impairment. The findings have important implications for preventing cognitive impairment in elder adults based on the long-term trajectories of changes in CVRFs.

Association between cannabis use and blood pressure levels according to comorbidities and socioeconomic status

The associations between blood pressure and cannabis use remain inconsistent. The purpose of our study was to examine gender stratified associations of cannabis use and blood pressure [systolic, diastolic blood pressure (BP), pulse pressure (PP)] levels among the general UK Biobank population based study. Among 91,161 volunteers of the UK Biobank population, cannabis use status was assessed by questionnaire and range as heavy, moderate, low and never users. Associations between cannabis use and BP were estimated using multiple gender linear regressions. In adjusted covariates models, lifetime heavy cannabis use was associated with decrease in both SBP, DBP and PP in both genders, but with a higher effect among women (for SBP in men, b = − 1.09 (0.27), p < 0.001; in women, b = − 1.85 (0.36), p < 0.001; for DBP in men, b = − 0.50 (0.15), p < 0.001; in women, b = − 0.87 (0.17), p < 0.001; and for PP in men, b = − 0.60 (0.20), p < 0.001; in women, b = − 0.97 (0.27), p < 0.001. Among men, lower SBP and DBP levels were observed with participants without dyslipidemia and lower PP in participants with high income levels. Among women, lower SBP, DBP and PP were observed with current smokers, moderate/low alcohol levels and participants without dyslipidemia. Current cannabis use was associated with lower SBP levels in men (b = − 0.63 (0.25), p = 0.012) and in women (b = − 1.17 (0.31), p < 0.001). Same results were observed for DBP and PP. Negative association between BP in men was found but not in women. The small association in BP differences between heavy users and never users remains too small to adopt cannabis-blood pressure public policy in clinical practice.

Ascending aorta dilatation reduces the influence of elevated pulse pressure on left ventricular hypertrophy: findings from a Chinese elderly hypertensive population.

To determine the role of ascending aorta dilatation in the relationship between pulse pressure (PP) and left ventricular (LV) hypertrophy. A total of 1556 Chinese elderly hypertensive patients were retrospectively studied. Transthoracic echocardiography was used to obtain the aortic and cardiac structure measurements. In addition, brachial blood pressure was measured, and total arterial compliance, systemic vascular resistance, arterial elastance, and end-systolic LV elastance were calculated. The participants were divided into four groups according to the status of ascending aortic diameter and PP. LV mass index increased in succession in the four groups, i.e., the group with the normal aorta and lower PP, with the normal aorta and higher PP, with aortic dilatation and lower PP, and with aortic dilatation and higher PP (P trend < 0.001). Total arterial compliance-1, arterial elastance, and end-systolic LV elastance were slightly higher in the individuals with normal aorta compared to those with aortic dilatation, regardless of PP being lower or higher (P < 0.01). Compared to the group with the normal aorta and lower PP, individuals with aortic dilatation had a significantly increased multivariable adjusted risk of LV hypertrophy, and higher PP further exacerbated this risk [aortic dilatation with lower PP (OR = 1.75, 95% CI: 1.01-3.04) and aortic dilatation with higher PP (OR = 3.42, 95% CI: 2.03-5.77)]. In the relation between PP and LV mass index (β = 0.095, P < 0.001), -41.3% of the total effect was attributable to mediation by ascending aortic diameter (P < 0.0001). In Chinese elderly patients with hypertension, ascending aorta dilatation could reduce the influence of elevated PP on LV hypertrophy.

High pulse pressure impairs cerebral artery endothelial function in young, but not old, mice

One of the hallmarks of vascular aging is increased pulse pressure. This elevated pulse pressure is associated with deleterious effects on cerebral vascular function; however, it is unknown if age modulates the susceptibility to high pulse pressure. To examine the effects of age on the cerebral artery response to pulse pressure, we studied isolated cerebral arteries collected from young (6.1 ± 0.2 mo) and old (26.7 ± 0.5 mo) male C57BL/6 mice. Isolated cerebral arteries were exposed ex vivo to static pressure, low pulse pressure (25 mmHg), and high pulse pressure (50 mmHg). In cerebral arteries from young mice, endothelium-dependent dilation was similar between the static and low pulse pressure conditions. Exposure to high pulse pressure impaired endothelium-dependent dilation in cerebral arteries from young mice, mediated by less nitric oxide bioavailability and greater oxidative stress. Cerebral arteries from old mice had impaired cerebral artery endothelium-dependent dilation at static pressure compared with young cerebral arteries. However, exposure to low or high pulse pressure did not cause any further impairments to endothelium-dependent dilation in old cerebral arteries compared with static pressure. The old cerebral arteries had less distension during exposure to high pulse pressure and greater stiffness compared with young cerebral arteries. These results indicate that acute exposure to high pulse pressure impairs endothelium-dependent dilation in young, but not old, cerebral arteries. The greater stiffness of cerebral arteries from old mice potentially protects against the negative consequences of high pulse pressure.

Correlation of pulse pressure to demographic, anthropometric, hemodynamic, and biochemical variables governing cardiovascular health

Background: A parameter of arterial stiffness, the pulse pressure (PP) gets adversely affected by serum low-density lipoprotein but to know how do other indicators of cardiovascular health such as cholesterol ratio, adiposity, and serum endothelin are correlated to it, we planned this study. Aims and Objectives: The aim of the study was to study the correlation of PP to demographic, anthropometric, hemodynamic, and biochemical variables. Materials and Methods: This was an analytical, observational, and pilot study with 30 overweight/obese subjects as cases and 30 non-obese subjects as controls. Informed consent was duly taken. History and clinical examination helped to exclude cases with secondary cause of abnormal blood flow. Blood pressure measurement along with venous blood sampling for biochemical tests was done. Results: The two groups varied significantly in age, in hemodynamic parameters (systolic blood pressure [SBP], diastolic blood pressure and PP), and in anthropometric measurements (waist to hip ratio [WHR], body mass index) (P &lt; 0.001). The lipid profile did not differ significantly in the two groups except the cholesterol ratio (P = 0.001) but it was not significantly correlated to PP. A good proportion of cases had raised PP in comparison to control who mostly had low PP. No significant difference in serum endothelin levels was observed. A significant positive correlation of PP with SBP and WHR in both groups (weakened on controlling the age variable), and with age, only in cases was recorded. Conclusion: Visceral adiposity, SBP, and ageing are independent predictors of PP but with no endothelial damage. Partial correlation revealed a major role of ageing in causing arterial stiffness.

Inflammaging and Blood Pressure Profiles in Late Life: The Screening for CKD among Older People across Europe (SCOPE) Study.

The neutrophil-to-lymphocyte ratio (NLR) is a marker for systemic inflammation. Since inflammation plays a relevant role in vascular aging, the aim of this study was to investigate whether NLR is associated with blood pressure profiles in older adults. This study was performed within the framework of the SCOPE study including 2461 outpatients aged 75 years and over. Mean blood pressure values, namely systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were investigated across tertiles of NLR. Change in blood pressure levels in 2 years of follow-up were compared across categories of baseline NLR. Data of 2397 individuals were used, of which 1854 individuals had hypertension. Mean values of blood pressure did not differ across categories of baseline NLR in individuals without hypertension. Individuals with hypertension with a high-range NLR had lower SBP and PP when compared to those in low-range NLR (mean difference SBP -2.94 mmHg, p = 0.032 and PP -2.55 mmHg, p = 0.030). Mean change in blood pressure in 2 years did only slightly differ in non-clinically relevant ranges, when compared across tertiles of baseline NLR. NLR as a marker of inflammaging was not associated with unfavorable blood pressure profiles in older individuals with or without hypertension.

Pulse pressure trajectories predict brain microstructure in an APOE‐dependent manner among cognitively normal older adults

AbstractBackgroundArterial stiffness is associated with increased risk of cognitive decline and dementia in older adults; however, the mechanisms by which arterial stiffness impacts brain health remain unclear. We examined whether trajectories of pulse pressure (PP), a surrogate marker of arterial stiffness, beginning in midlife predicted brain microstructure at older age, using the multicompartment diffusion MRI technique restriction spectrum imaging (RSI). We assessed whether effects of PP on executive function were mediated by brain microstructure, and whether APOE genotype modified associations between PP and microstructure.MethodWe included 146 cognitively normal adults (mean age=76.6, SD=6.8 years) who underwent RSI and cognitive testing in 2014‐2016 and measurements of PP up to eight times before MRI, from 1984‐2016. Participants were classified according to PP trajectory using latent class growth modeling. Restricted isotropic diffusion (RI), neurite density, isotropic free water (IFW), and hindered isotropic diffusion (HI) were computed in five subcortical regions and 15 white matter tracts. Multiple linear regression examined associations between PP trajectories and microstructure, and between microstructure and Trails B performance. Mediation analyses, adjusted for covariates, evaluated whether microstructure mediated effects of PP trajectories on executive function. Age‐and‐sex‐adjusted partial correlations tested associations between continuous PP and RSI metrics by APOE genotype (ε4 carriers versus non‐carriers).ResultParticipants with high PP trajectories (n=50) had lower RI and higher HI and IFW in multiple subcortical regions and fiber tracts compared to those with low PP trajectories (n=96), and of these, eight were also associated with Trails B performance. Associations between high PP trajectories and worse executive function were mediated by lower RI in the amygdala (βa*βb=4.13, 95%CI=0.91‐11.01) and in several fiber tracts including the parachippocampal cingulum (βa*βb=3.77, 95%CI=0.95‐9.93) and fornix (βa*βb=3.71, 95%CI=0.59‐10.19). High PP more strongly correlated with lower RI in the hippocampus, uncinate fasciculus, and inferior fronto‐occipital fasciculus (IFO); with high IFW in the IFO and superior corticostriatal fasciculus, and with high amygdala HI, among APOE4 ε4 carriers than non‐carriers (Figure).ConclusionProlonged elevated PP predicts subcortical and white mater microstructural abnormalities, particularly for those at greater risk for dementia, and may contribute to impaired executive function via microstructural injury.

High Pulse Pressure Decreases Cardiopulmonary Ability among Older Chinese Patients with Primary Hypertension.

There is limited information regarding the reference values for cardiopulmonary exercise testing (CPX) variables in patients with primary hypertension. Our aim was to provide such values. In this single-center, retrospective study, we included 635 patients (male, 53.7%; mean ± standard deviation age, 62.1 ± 12.6 years) who completed maximal ramp incremental CPX using cycle ergometry at the Rui An Hospital of Traditional Chinese Medicine from August 1, 2018, to December 31, 2021. The patients were classified into two groups based on pulse pressure (PP): (1) patients with a low PP ≤ 60 mmHg (n = 324) and (2) patients with a high PP > 60 mmHg (n = 311). Stepwise linear regression was used to fit the equations of the key CPX variables. CPX was self-interrupted owing to fatigue by 64.5% (low PP) and 72.0% (high PP) of patients (χ2 analysis, P = 0.05). The anaerobic threshold (AT) could not be determined in 3.7% and 7.7%, respectively (χ2 analysis, P = 0.038). Peak oxygen consumption (VO2), carbon dioxide production, ventilation/minute, work rate, and VO2 at the AT were associated with age, weight, and sex. Moreover, a high PP was associated with impaired anaerobic exercise ability, as indicated by the reduced peak VO2, peak VE, and absolute peak work rate. Compared with prior research of a healthy population, patients with primary hypertension in this study exhibited impaired cardiopulmonary ability both at rest and during exercise, especially in the high PP group. The reference values and predictive equations for CPX variables provide a framework for interpreting the response to maximal ramp incremental cycle ergometry among older Chinese patients with primary hypertension.

Pulse pressure trajectories predict brain microstructure in community-dwelling older adults: Associations with executive function and modification by APOE.

Effects of chronic arterial stiffness on brain aging remain unclear. We, therefore, examined whether long-term trajectories of pulse pressure (PP) predicted brain microstructure, microstructure mediated PP-executive function associations, and APOE genotype modified PP-microstructure associations. We examined associations of PP trajectories with brain microstructure measured using restriction spectrum imaging in 146 community-dwelling older adults, whether microstructure mediated PP trajectory-executive function associations, and whether PP-restriction spectrum imaging correlations were modified by APOE-ε4 status. Participants with trajectories of high PP had lower restricted isotropic diffusion (RI) compared to those with low PP trajectories and PP-executive function associations were mediated by subcortical and white matter RI. High PP more strongly correlated with lower RI and higher hindered diffusion among APOE-ε4 carriers than non-carriers. Prolonged elevated PP predicts microstructural abnormalities which may contribute to impaired executive function. APOE-ε4 carriers may be most vulnerable to the adverse effects of PP on brain microstructure.

Early Low Pulse Pressure in VA-ECMO Is Associated with Acute Brain Injury.

Pulse pressure is a dynamic marker of cardiovascular function and is often impaired in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Pulsatile blood flow also serves as a regulator of vascular endothelium, and continuous-flow mechanical circulatory support can lead to endothelial dysfunction. We explored the impact of early low pulse pressure on occurrence of acute brain injury (ABI) in VA-ECMO. We conducted a retrospective analysis of adults with VA-ECMO at a tertiary care center between July 2016 and January 2021. Patients underwent standardized multimodal neuromonitoring throughout ECMO support. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressures were recorded every 15min. Low pulse pressure was defined as a median pulse pressure < 20mmHg in the first 12h of ECMO. Multivariable logistic regression was performed to investigate the association between pulse pressure and ABI. We analyzed 5138 blood pressure measurements from 123 (median age 63; 63% male) VA-ECMO patients (54% peripheral; 46% central cannulation), of whom 41 (33%) experienced ABI. Individual ABIs were as follows: ischemic stroke (n = 18, 15%), hypoxic ischemic brain injury (n = 14, 11%), seizure (n = 8, 7%), intracranial hemorrhage (n = 7, 6%), cerebral edema (n = 7, 6%), and brain death (n = 2, 2%). Fifty-eight (47%) patients had low pulse pressure. In a multivariable model adjusting for preselected covariates, including cannulation strategy (central vs. peripheral), lactate on ECMO day 1, and left ventricle venting strategy, low pulse pressure was independently associated with ABI (adjusted odds ratio 2.57, 95% confidence interval 1.05-6.24). In a model with the same covariates, every 10-mmHg decrease in pulse pressure was associated with 31% increased odds of ABI (95% confidence interval 1.01-1.68). In a sensitivity analysis model adjusting for systolic pressure, pulse pressure remained significantly associated with ABI. Early low pulse pressure (< 20mmHg) was associated with ABI in VA-ECMO patients. Low pulse pressure may serve as a marker of ABI risk, which necessitates close neuromonitoring for early detection.

The relationship between pulse pressure with plasma PCSK9 and interleukin-6 among patients with acute ischemic stroke and dyslipidemia

Background and purposeA high plasma concentration of proprotein convertase subtilisin/kexin type 9 is characteristic of a prothrombotic state in cardiovascular diseases. Elevated inflammatory markers, such as interleukin-6, are associated with worse outcomes after ischemic stroke. We aimed to study the role of plasma PCSK9 and IL-6 in acute ischemic stroke with dyslipidemia. MethodsWe divided 123 enrolled patients with first-ever acute ischemic stroke into normotensive and high blood pressure groups and further into high and low pulse pressure subgroups. Clinical characteristics and inflammatory and metabolic parameters, including plasma PCSK9 and IL-6, were recorded. ResultsAfter the analysis of the normotensive and BP groups, there were positive correlations between PP and carotid stenosis (P = 0.031) and plaque numbers (P = 0.013) and between National Institute of Health Stroke Scale scores (P = 0.019) and carotid stenosis severity (P = 0.021) and resistance index (P = 0.04). There was a significant association between plasma cholesterol and PCSK9 (P = 0.044) in the low PP subgroup and IL-6 (P = 0.042) in the high PP subgroup. ConclusionsOur findings indicated that plasma PCSK9 levels were associated with the low PP subgroup, while IL-6 was associated with the high PP subgroup. Dyslipidemia control is also necessary for those who had a stroke and who have high PP. Further investigation to assess the role of PCSK9 and IL-6 in patients with stroke is required for early treatment and secondary prevention.

Selected autonomic signs and symptoms as risk markers for phenoconversion and functional dependence in prodromal Parkinson's disease.

To determine whether dysautonomia can stratify individuals with other prodromal markers of Parkinson's disease (PD) for risk of phenoconversion and functional decline, which may help identify subpopulations appropriate for experimental studies. Data were obtained from Parkinson's Progression Markers Initiative. Cohorts without PD but with at-risk features were included (hyposmia and/or rapid-eye-movement-sleep behavior disorder, LRRK2 gene mutation, GBA gene mutation). Dysautonomia measures included Scales-for-Outcomes-in-Parkinson's-Disease Autonomic (SCOPA-AUT), seven SCOPA-AUT subscales, and cardiovascular dysfunction (supine hypertension, low pulse pressure, neurogenic orthostatic hypotension). Outcome measures were phenoconversion and Schwab-and-England Activities-of-Daily-Living (SE-ADL) ≤ 70, which indicates functional dependence. Cox proportional-hazards regression was used to evaluate survival to phenoconversion/SE-ADL ≤ 70 for each dysautonomia measure. If a significant association was identified, a likelihood-ratio test was employed to evaluate whether a significant interaction existed between the measure and cohort. If so, regression analysis was repeated stratified by cohort. Median follow-up was 30months. On multivariable analysis, gastrointestinal and female sexual dysfunction subscales were associated with increased risk of phenoconversion, while the cardiovascular subscale and neurogenic orthostatic hypotension were associated with increased risk of SE-ADL ≤ 70; respective hazard ratios (95% confidence intervals) were 1.13 (1.01-1.27), 3.26 (1.39-7.61), 1.87 (1.16-2.99), 5.45 (1.40-21.25). Only the association between the cardiovascular subscale and SE-ADL ≤ 70 was modified by cohort. Symptoms of gastrointestinal and female sexual dysfunction predict phenoconversion in individuals with other risk markers for PD, while signs and symptoms of cardiovascular dysfunction may be associated with functional decline.

Inflammatory And Cardiovascular Correlates Of Physical Activity In Older Adults Living With Hiv

BACKGROUND: Inflammatory biomarkers are known indicators of oxidative stress contributing to cardiovascular diseases (CVD) in older people living with HIV (OPLWH). Physical activity (PA) may reduce these markers in OPLWH, however, little is known about the association between PA with inflammatory and CVD biomarkers in this high-risk group. PURPOSE: To examine inflammatory and CVD biomarker correlates of PA in OPLWH in the Deep South. METHODS: This study utilized data from a larger parent study in the Birmingham, Alabama area. Biomarker assays were conducted for inflammatory markers (TNF-alpha, CRP, IL-6). Participants self-reported PA (International Physical Activity Questionnaire), sociodemographics, and comorbidities. PA correlates were examined using Spearman rank correlations by PA duration and volume at various intensities. RESULTS: 101 HIV+ participants were assessed in the present study (age, 57.91[6.58] years; male, 58.20%; African American, 71.59%). Among OPLWH, sitting was associated with greater triglycerides (rho = 0.27, p < 0.001), IL-6 (rho = 0.20, p < 0.05), and TNF-alpha (rho = 0.23, p < 0.05). In OPLWH, more time engaged in walking and moderate-intensity exercise was associated with lower systolic blood pressure (rho = -0.21, p < 0.05) and pulse pressure (rho = -0.22 and -0.19, respectively; p < 0.05), while more time engaged in vigorous intensity was associated with lower TNF-alpha (rho = -0.19; p < 0.05). Among OPLWH, engaging in more volume of walking and moderate-intensity physical activity was associated with lower systolic (rho = -0.21, p < 0.05), while engaging in more volume of moderate-intensity and vigorous-intensity was associated with lower diastolic blood pressures (rho = -0.19 and -0.20, respectively, p < 0.05). Lastly, walking was associated with lower pulse pressure (rho = -0.21, p < 0.05), and vigorous intensity was associated with lower TNF-alpha levels (rho = -0.20, p < 0.05). CONCLUSION: Higher PA duration and volume were correlated with lower levels of inflammatory and CVD biomarkers in OPLWH. These findings suggest engaging in more duration and volume of PA may aid in potentially overcoming the metabolic, cardiovascular, and inflammatory derangement associated with HIV.

Pulse pressure within the first 2 days of veno-arterial extracorporeal membrane oxygenation is predictive of death prior to hospital discharge, renal dysfunction requiring dialysis and pulmonary oedema.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) flows are titrated to achieve adequate perfusion while attempting to ideally maintain arterial pulse pressure (PP). We assessed risk in patients with low PP defined as <10mmHg within the first 2days of support. Demographics, haemodynamics, echocardiographic and radiological findings were recorded retrospectively in cases conducted between 2014 and 2016. Outcomes were hospital mortality, requirement for renal replacement therapy (RRT) and severe pulmonary oedema (PO). Of 101 patients, 66.3% were male, mean age was 56 (range 18-71years), mean duration of support was 6.3 days ± 4.1days, 37.6% died prior to hospital discharge, 39.6% needed RRT and 11.9% had severe PO. Areas under the receiver operating curves of PP at 48h for hospital mortality, RRT and severe PO were (respectively): 0.69 (95% CI 0.58-0.80, p = .001), 0.64 (95% CI 0.50-0.77, p = .044), 0.69 (95% CI 0.55-0.82, p = .009). The odds ratio for mortality, RRT, severe PO for those with low PP were (respectively) 2.8 (95% CI 1.01-7.5, p = .04), 3.1 (95% CI 1.11-8.40, p = .026), 7.6 (95% CI 2.06-27.89, p = .001). Central venous pressure, mean arterial pressure were not predictive. PP during the first 2days of support is predictive of clinically important outcomes in patients supported with VA-ECMO.

Inframe insertion and splice site variants in MFGE8 associate with protection against coronary atherosclerosis

Cardiovascular diseases are the leading cause of premature death and disability worldwide, with both genetic and environmental determinants. While genome-wide association studies have identified multiple genetic loci associated with cardiovascular diseases, exact genes driving these associations remain mostly uncovered. Due to Finland’s population history, many deleterious and high-impact variants are enriched in the Finnish population giving a possibility to find genetic associations for protein-truncating variants that likely tie the association to a gene and that would not be detected elsewhere. In a large Finnish biobank study FinnGen, we identified an association between an inframe insertion rs534125149 in MFGE8 (encoding lactadherin) and protection against coronary atherosclerosis. This variant is highly enriched in Finland, and the protective association was replicated in meta-analysis of BioBank Japan and Estonian biobank. Additionally, we identified a protective association between splice acceptor variant rs201988637 in MFGE8 and coronary atherosclerosis, independent of the rs534125149, with no significant risk-increasing associations. This variant was also associated with lower pulse pressure, pointing towards a function of MFGE8 in arterial aging also in humans in addition to previous evidence in mice. In conclusion, our results suggest that inhibiting the production of lactadherin could lower the risk for coronary heart disease substantially.

Determinants of peripheral artery disease among persons with diabetes mellitus in north central Nigeria

Peripheral artery disease (PAD) is one of the leading causes of non-traumatic amputation worldwide and a major cause of depression. It is therefore imperative to identify the determinants of PAD so as to adopt strategies for its early prevention. The aim of this study therefore, is to assess the determinants of PAD among persons with diabetes mellitus (DM). This is a cross-sectional study aimed at identifying the determinants of PAD among persons with DM. One thousand and forty (1,040) participants were consecutively recruited following consent from participants and waiver of ethical approval. Relevant medical history, anthropometric measurements, other clinical examinations including measurement of ankle-brachial index (ABI), and were undertaken. IBM SPSS version 23 was used for statistical analysis and logistic regression was used to assess for the determinants of PAD. Significance level used was p &lt; 0.05. Following logistic regression analysis, significant determinants of PAD included age with odds ratio (OR) 1.51, Confidence Interval (CI) 1.18-2.34, p=0.033; duration of DM (OR 1.51, CI 1.23-1.85, p&lt;0.001); positive neuropathic symptoms (OR 2.94, CI 1.94-9.23, p=0.045); central obesity (OR 9.77, CI 5.07-18.82, p&lt;0.001); poor SBP control (OR 2.47, CI 1.26-4.87, p=0.016); poor DBP control (OR 2.45, CI 1.24-4.84, p=0.010); poor HbA1c control (OR 2.59, CI 1.50-5.71, p&lt;0.001); and poor 2HrPP control (OR 3.43, CI 1.79-6.56, p&lt;0.001). Significant inverse determinants of PAD included pulse pressure (OR 0.78, CI 0.67-0.99, p&lt;0.001), statins (OR 3.01, CI 1.99-9.19, p=0.023), and antiplatelets (OR 7.14, CI 3.03-15.61, p=0.008). Significant determinants of PAD included age, duration of DM, positive neuropathic symptoms, central obesity, and poor control of, DBP, and 2HrP. Pulse pressure was however, found to be a significant inverse determinant of PAD which means that low pulse pressure may predispose to PAD. Finally, antiplatelets and statins use were significant inverse determinants of PAD, i.e., they may be protective against PAD. It is recommended therefore, that patients be placed on antiplatelets and statins as early as possible, and in line with extant guidelines.

CARC13: Early Low Pulsatility in VA-ECMO is Associated with Acute Brain Injury

Background: Pulse pressure (or pulsatility) is a dynamic marker of cardiovascular function and is often decreased in patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO), which provides non-pulsatile flow. We explored the impact of pulse pressure on development of acute brain injury (ABI) in VA-ECMO patients. Methods: We retrospectively analyzed all adult (≥18 years old) patients receiving VA-ECMO at a single tertiary care center between 7/2016 and 1/2021. All patients received routine neurocritical care consultations with standardized neuromonitoring. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressure (BP) was recorded every 15 minutes during the first 24 hours after ECMO initiation. Pulse pressure (systolic minus diastolic pressure) was categorized as: very low (<10mmHg), low (1029mmHg), moderate (30-44mmHg), and high (≥45mmHg). Multivariable logistic regression, controlling for baseline illness severity, operative characteristics, and left ventricle (LV) venting strategy, was performed for the association of pulse pressure with ABI. LV venting strategies included intra-aortic balloon pump (IABP), percutaneous ventricular assist device, right superior pulmonary vein, and left ventricle apex vents. Results: We collected 9,179 pressure measurements from 123 VA-ECMO patients (median age=63, 63% male), of which 41 (33%) experienced ABI. Demographics, baseline clinical characteristics, and pre-ECMO arterial blood gases were not significantly different between those with and without ABI. Those with ABI had a lower median pulse pressure than those without (20 mmHg vs. 32, p=0.038). In a multivariable model controlling for cannulation site, preECMO lactate, and left ventricle venting strategy, low (adjusted odds ratio/aOR=7.04, 95%CI: 1.72-28.82, p=0.007) and very low pulse pressure (aOR=5.14, 95%CI: 1.18-22.34, p=0.029) were associated with ABI (Figure 1). In a model with the same covariates, every 10-mmHg decrease in pulse pressure was associated with a 1.29 increased adjusted odds of ABI (95%CI: 1.00-1.65, p=0.047) (Figure 2). In a sensitivity analysis, adjusting for systolic BP yielded similar associations between pulse pressure and ABI, suggesting pulse pressure acts independently of BP in mediating ABI. Conclusions: Decreased pulsatility in the first 24 hours of VA-ECMO was associated with ABI. Special attention should be given to management practices which sustain sufficient pulse pressure early during ECMO. Figure 1. Forest plot for multivariable model of pulse pressure and acute brain injury (ABI), with the covariates of central cannulation, lactate on ECMO day 1, and left ventricle venting strategy. Covariates are not shown in the figure. Dots represent adjusted odds ratios and brackets represent 95% confidence intervals. Low and very low pulse pressure were associated with increased odds of ABI. This model had a C-index of 0.76. Figure 2. Multivariable logistic regression model with pulse pressure treated as a continuous variable, with the covariates of central cannulation, lactate on ECMO day 1, and left ventricle venting strategy. The adjusted relative odds of acute brain injury decrease as pulse pressure increases.