Ambulatory pulse pressure and its contributors in autosomal dominant polycystic kidney disease.

BACKGROUND: Pulse pressure (PP) is a pulsatile component of blood pressure (BP), strongly correlated with arterial stiffness (AS) and impacting prognosis. Disproportionally increased PP values in individuals with autosomal dominant polycystic kidney disease (ADPKD) should be expected, given the multifactorial cardiovascular involvement in the natural course of this disease. OBJECTIVES: To investigate ambulatory PP in a group of ADPKD patients, and to examine the impact of age, sex, kidney function, hypertension, circadian rhythm, and antihypertensive drugs (AH) on studied parameters. MATERIAL AND METHODS: A total of 130 ADPKD patients (median age 41 years, 35% men) who underwent 24-hour BP measurement with portable oscillometer Spacelabs 90217, were included in the study and their recordings were retrospectively analyzed. Demographic data and the medical history including antihypertensive treatment were collected, ADPKD was diagnosed based on the criteria by Pei et al., and estimated glomerular filtration rate (eGFR) was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: Pulse pressure in the whole group was 46 (IQR: 42-53) mm Hg and it was significantly higher in men than in women and during the day compared to nighttime. There was a negative correlation of PP with eGFR and a positive correlation with age. Pulse pressure was not different in ADPKD patients with or without a diagnosis of hypertension. CONCLUSION: Ambulatory PP is not substantially increased in ADPKD patients across different stages of CKD. It follows a regular pattern of being increased with age, male sex, daytime, and decreasing eGFR, but not with the diagnosis of hypertension.

Metabolomic Signature of Early Vascular Aging (EVA) in Hypertension.

Arterial stiffening is a hallmark of early vascular aging (EVA) syndrome and an independent predictor of cardiovascular morbidity and mortality. In this case-control study we sought to identify plasma metabolites associated with EVA syndrome in the setting of hypertension. An untargeted metabolomic approach was used to identify plasma metabolites in an age-, BMI-, and sex-matched groups of EVA (n = 79) and non-EVA (n = 73) individuals with hypertension. After raw data processing and filtration, 497 putative compounds were characterized, out of which 4 were identified as lysophosphaditylcholines (LPCs) [LPC (18:2), LPC (16:0), LPC (18:0), and LPC (18:1)]. A main finding of this study shows that identified LPCs were independently associated with EVA status. Although LPCs have been shown previously to be positively associated with inflammation and atherosclerosis, we observed that hypertensive individuals characterized by 4 down-regulated LPCs had 3.8 times higher risk of EVA compared to those with higher LPC levels (OR = 3.8, 95% CI 1.7-8.5, P < 0.001). Our results provide new insights into a metabolomic phenotype of vascular aging and warrants further investigation of negative association of LPCs with EVA status. This study suggests that LPCs are potential candidates to be considered for further evaluation and validation as predictors of EVA in patients with hypertension.

Aortic stiffness is not only associated with structural but also functional parameters of retinal microcirculation.

OBJECTIVE: The aim of the study was to test the hypothesis that alterations in large arteries are associated with microvascular remodelling and decreased retinal capillary blood flow. METHODS: The study group comprised of 88 patients with essential hypertension and 32 healthy controls. Retinal microcirculation was evaluated by scanning laser Doppler flowmetry. Macrovascular changes were assessed on the basis of arterial stiffness measurement (carotid-femoral pulse wave velocity), its hemodynamic consequences (central pulse pressure, augmentation pressure, augmentation index) and intima media thickness of common carotid artery. RESULTS: Pulse wave velocity was inversely correlated to mean retinal capillary blood flow in hypertensive patients (R = -0.32, p < 0.01). This relationship remained significant in multivariate regression analysis after adjustment for age, sex, central systolic blood pressure (BP) and body mass index (ß = -31.27, p < 0.001). Lumen diameter (LD) of retinal arterioles was significantly smaller in hypertensive then normotensive subjects (79.4 vs. 83.8, p = 0.03). Central and brachial systolic, diastolic and mean BPs were significantly correlated with LD and outer diameter of retinal arterioles. The relationship between LD and central BPs remained significant in multivariate analysis (ß = -0.15, p = 0.03 for cSBP; ß = -0.22, p = 0.04 for cDBP; ß = -0.21, p = 0.03 for cMBP). Moreover, in a subgroup with cardiac damage central and brachial pulse pressure were positively associated with retinal wall thickness, wall cross sectional area, and wall to lumen ratio. CONCLUSION: In conclusion, the study provides a strong evidence that microcirculation is coupled with macrocirculation not only in terms of structural but also functional parameters.

Untargeted Metabolomics Provides Insight into the Mechanisms Underlying Resistant Hypertension.

BACKGROUND: Resistant hypertension (RH) affects about 15-20% of treated hypertensive patients worldwide. RH increases the risk of cardiovascular events such as myocardial infarction and stroke by 50%. The pathological mechanisms underlying resistance to treatment are still poorly understood. OBJECTIVE: The main goal of this pilot study was to determine and compare plasma metabolomic profiles in resistant and non-resistant hypertensive patients. METHODS: We applied untargeted metabolomic profiling in plasma samples collected from 69 subjects with RH and 81 subjects with controlled hypertension. To confirm patients' compliance to antihypertensive treatment, levels of selected drugs and their metabolites were determined in plasma samples with the LC-ESI-TOF/MS technique. RESULTS: The results showed no statistically significant differences in the administration of antihypertensive drug in the compared groups. We identified 19 up-regulated and 13 downregulated metabolites in the RH. CONCLUSION: The metabolites altered in RH are linked to oxidative stress and inflammation, endothelium dysfunction, vasoconstriction and cell proliferation. Our results may generate new hypothesis about RH development and progression.

Lumen narrowing and increased wall to lumen ratio of retinal microcirculation are valuable biomarkers of hypertension-mediated cardiac damage.

Purpose: In the course of hypertension, left ventricular hypertrophy and diastolic dysfunction develop very often and may progress toward heart failure. The aim of the study was to analyze the relationship between abnormalities of retinal microcirculation and cardiac damage defined as left ventricular hypertrophy and/or diastolic dysfunction.Materials and methods: The study comprised 88 patients with essential hypertension. The group was divided into two subgroups: hypertensives without cardiac damage (n = 55) and with cardiac damage (n = 33). Control group comprised 32 normotensive subjects. Scanning laser Doppler flowmetry was used to evaluate retinal microcirculation. Echocardiography was used to assess cardiac damage.Results: Lumen diameter of retinal arterioles was significantly smaller in patients with cardiac damage vs. controls (77 vs. 84 µm, p = 0.02). Additionally, there was an evident trend with respect to lumen diameter (LD) across all three studied subgroups; i.e.: the smallest dimeters were present in cardiac damage patients, moderate size in hypertensives' without cardiac damage, and the largest diameters in healthy controls (pfor trend < 0.01). Lumen diameter was inversely correlated with cardiac intraventricular septum diameter (R = -0.25, p = 0.02), left ventricular mass (R = -0.24, p = 0.02), and left atrial volume (R = -0.22, p = 0.04). Wall to lumen ratio was associated with intraventricular septum diameter (R = 0.21, p = 0.044) and left atrial volume (R = 0.21, p = 0.045). In multivariable regression analysis, lumen diameter was independently associated with intraventricular septum diameter (ß = -0.05, p = 0.03), left ventricular mass (ß = -1.15, p = 0.04), and left atrial volume (ß = -0.42, p = 0.047); wall to lumen ratio was independently associated with intraventricular septum diameter (ß = 3.67, p = 0.02) and left atrial volume (ß = 30.0, p = 0.04).Conclusions: In conclusion, retinal arterioles lumen diameter and wall to lumen ratio were independent biomarkers of cardiac damage. Retinal examination performed by means of scanning laser Doppler flowmetry might be a valuable tool to improve cardiovascular risk stratification of hypertensive patients.

Impact of orthostatic hypotension and antihypertensive drug treatment on total and cardiovascular mortality in a very elderly community-dwelling population.

OBJECTIVE: The aim of this study was to examine the relationship between orthostatic hypotension, cardiovascular drug intake and mortality in a very elderly community-dwelling population (>80 years of age). METHODS: In 2013-2014, 224 (71 M, 31.7%) 80-year-old individuals from one primary care practice were invited to participate. Basic clinical information was gathered and blood pressure (BP) measurements were performed while sitting and after 1 and 3 min in the standing position on 209 patients. The individuals were followed till December 2016. RESULTS: Orthostatic hypotension was present, depending on applied definition, in 34.5% of the individuals at 1 min, 38.3% at 3 min; 44.9% on either 1 or 3 min, and 27.8% individuals in both measurements. Sixty-nine (30.8%) individuals died during the follow-up. Presence of orthostatic hypotension, irrespective of definition, did not have any significant association with the mortality risk in all groups. Intensive hypertension treatment (more than two drugs versus none) was associated with longer survival. In a multivariate logistic regression analysis, only age and presence of coronary heart disease/congestive heart failure had a negative predictive value on mortality. In both treated and untreated individuals, presence of orthostatic hypotension was not linked to mortality. CONCLUSION: Although orthostatic hypotension is very common among the very elderly, its presence is not related to increased risk of death (all-cause/cardiovascular). Intensively treated elderly patients had significantly longer survival time than untreated individuals.

Prevalence and distribution of left ventricular diastolic dysfunction in treated patients with long-lasting hypertension.

BACKGROUND: Although the presence of sub-clinical left ventricular diastolic dysfunction (LVDD) increases cardiovascular risk, the current ESH/ESC guidelines do not include the presence of this condition in the list of target organ damage or cardiovascular risk charts dedicated to the hypertensive population. Several conditions may predict the LVDD occurrence, however, clustering of these factors with hypertension makes the relationship less clear. Therefore, the aim of this study was to evaluate both the occurrence and the severity of diastolic dysfunction in a large cohort of treated hypertensives. METHODS: We retrospectively analyzed records of 610 hypertensive participants of the CARE NORTH Study who consented to echocardiography and were free of overt cardiovascular disease. Mean age was 54.0 ± 13.9 years (mean ± SD), BMI 29.7 ± 4.8 kg/m2. The exclusion criteria were: established heart failure, LVEF <45%, coronary revascularization, valvular defect, atrial fibrillation, or stroke. The staging of LVDD was based on comprehensive transthoracic echocardiographic measurements. RESULTS: 49.7% percent of the patients had normal diastolic function (38.8% vs. 59.0%, females (F) vs. males (M), respectively; p < .001). Grade 1 LVDD was documented in 24.4% (27.8% and 21.6%; F and M; p = .08) and grade 2 LVDD in 19.3% (24.9% and 14.6%; F and M; p = .001) of the patients. None were diagnosed with grade 3 LVDD. In the logistic regression model, female sex, advancing age, obesity status, established diabetes mellitus, higher 24-hour SBP, and increasing LVMI were identified as the independent variables increasing the odds for the presence of LVDD, whereas blood-lowering therapy attenuated the risk. CONCLUSIONS: There is an unexpectedly high prevalence of different forms of diastolic dysfunction in treated hypertensive patients who are free of overt cardiovascular disease.

A multilocus genetic risk score is associated with arterial stiffness in hypertensive patients: the CARE NORTH study.

INTRODUCTION: Arterial stiffness is recognized as an intermediate phenotype and predictor of cardiovascular disease. Arterial stiffness is complex in origin with contributions from lifestyle and genetic factors. However, the association between single nucleotide polymorphisms (SNPs) and arterial stiffness remains unclear. OBJECTIVE: The aim is to assess whether a multilocus genetic risk score (GRS), composed of selected SNPs linked to cardiovascular traits and outcomes, is associated with arterial stiffness in patients with hypertension. DESIGN AND METHODS: This study included 730 participants derived from the CARE NORTH study. The arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cfPWV). An adjusted linear regression was used to evaluate the association between cfPWV and each individual SNP using multiple genetic models. The association between a constructed GRS and cfPWV was tested in an unadjusted and adjusted model. RESULTS: We selected 13 SNPs found to be associated with cfPWV (P < .05): 6 SNPs in additive, 4 SNPs in recessive and 3 SNPs in dominant mode of inheritance. The GRS based on these SNPs was positively associated with cfPWV both in unadjusted and adjusted models (ß = 0.2 m/s, 95% CI 0.11 - 0.29, P = 7.6 × 10 and ß = 0.22 m/s, 95% CI 0.15 - 0.28, P = 1.4 × 10, respectively). The GRS explained an additional 3.6% cfPWV variance above clinical covariates. CONCLUSION: We demonstrate that the GRS composed of 13 SNPs related to cardiovascular phenotypes is associated with an increased arterial stiffness in hypertensive patients. Our findings may help to clarify genetic basis of arterial stiffening and provide insight into mechanisms underlying this phenotype.

Visualizing Carotid Bodies With Doppler Ultrasound Versus CT Angiography: Preliminary Study.

OBJECTIVE: The purpose of this article is to evaluate the utility of ultrasound in identifying carotid bodies (CBs) in patients with drug-resistant arterial hypertension. SUBJECTS AND METHODS: We enrolled 13 patients with drug-resistant hypertension into a trial for surgical CB excision. CT angiography (CTA) and Doppler ultrasound (DUS) of the cervical arteries were performed before surgery. CBs were identified in a blind manner at both CTA and DUS. CBs were defined at CTA as ovoid avidly enhancing structures at the inferomedial aspect of the carotid bifurcation. At DUS, CBs were defined as ovoid solid structures in the inferomedial aspect of the bifurcation. RESULTS: CBs were identified in 12 of 13 patients (23/26 sides) using CTA and in 11 of 13 patients (18/26 sides) using DUS. Identification of CB with DUS and CTA correlated in 17 of 18 cases; in one instance, CB was identified with DUS but not CTA. There was no statistically significant difference in size and volume of CB measured by both methods. CONCLUSION: Noncarcinogenic CBs can be visualized using DUS, with good correlation of size and location compared with CTA. The findings show that DUS can be reliably used to further examine the role of CBs in cardiovascular disorders and can be used in conjunction with therapies that target CBs.

Serum of obstructive sleep apnea patients impairs human coronary endothelial cell migration.

INTRODUCTION: Endothelial cell migration and proliferation play an important role in the growth and development of new blood vessels and endothelium healing. This process occurs in response to injury, inflammation and immune reactions. Dysfunction of the endothelium may play a significant role in development and progression of cardiovascular disease related to sleep-disordered breathing. The aim of our study was to evaluate the chemo-attractant activity of serum from obstructive sleep apnea (OSA) and normal subjects on coronary artery endothelial cell migration. MATERIAL AND METHODS: We studied 12 severe OSA patients, free of other co-morbidities and on no treatment, along with 12 age-, body mass index, and gender matched healthy controls. Blood was collected at three time points: at 21:00 before sleep, at 6:00 after waking from sleep, and at 11:00 (after 5 h of normal daytime activity). Serum chemo-attractant activity for human coronary endothelial cells was assessed using a colorimetric cell migration assay kit. RESULTS: In healthy subjects, serum chemo-attractant activity peaked in the morning after waking from sleep (p = 0.02). This early morning increase was blunted in severe OSA subjects, in whom chemo-attractant activity was weaker than in normal controls (p = 0.02), and did not change significantly at the different time-points (p < 0.001 vs. controls). CONCLUSIONS: Chemo-attractant activity of the serum from OSA patients is lower compared to serum from healthy subjects, especially in the morning. Altered chemo-attractant serum activity may conceivably contribute to the impairment of endothelial function in obstructive sleep apnea patients.

Prevalence and characteristics of OSAFED syndrome in atrial fibrillation primary care patients.

BACKGROUND: Atrial fibrillation (AF) constitutes the most prevalent arrhythmia, affecting up-to 2% of the general population. Apart from well-established risk factors that increase the odds for the development of AF, e.g. age or arterial hypertension, recent analyses indicate that obstructive sleep apnoea (OSA) may independently, negatively modify the arrhythmia occur-rence profile. Concurrently, erectile dysfunction (ED) is a commonly neglected, potent marker of cardiovascular risk, which considerably worsens men's psychological state. Unrecognised or untreated ED results in substantial deterioration of the patient's therapeutic programme adherence. Because AF, OSA, and ED share multiple risk factors and clinical consequences, in 2013 the concept of their frequent concurrence - OSAFED syndrome - was proposed. AIM: The aim of the study was to evaluate the prevalence of OSAFED patients with AF in primary care practice. METHODS: Retrospective analysis was carried out of data from primary care physician charts (NZOZ Esculap Gniewkowo, central Poland) including 1372 men aged 40-65 years. The primary goal was to determine the diagnosis of paroxysmal and/or perma-nent AF, which was followed by sleep apnoea screening (polygraphy) and erectile function evaluation (IIED-5 questionnaire). RESULTS: Twenty-one (1.5%) patients with documented AF were identified. Based on the sleep-polygraphic studies, 14 (67%) of them had confirmation of OSA with mean apnoea-hypopnea index (AHI) equal to 27.5 ± 17.1. Furthermore, 11 (52%) patients met the OSAFED syndrome criteria. Patients with OSAFED syndrome had a mean score in IIEF-5 of 11.6 ± 3.5. The OSAFED-patients who were not diagnosed with all the of the syndrome components prior to the study-enrolment were characterised by substantially lower fat excess compared to their counterparts with already established OSAFED (body mass index: 30.1 ± 4.9 vs. 37.7 ± 3.9 kg/m², respectively, p = 0.03). CONCLUSIONS: Frequently coexisting OSAFED syndrome components in all AF patients from the primary care setting should encourage a more active search for OSA and ED in patients with any documented form of AF. Most of the studied patients did not have the diagnosis of OSA nor ED done prior to participation in the study.

Unilateral Carotid Body Resection in Resistant Hypertension: A Safety and Feasibility Trial.

Animal and human data indicate pathological afferent signaling emanating from the carotid body that drives sympathetically mediated elevations in blood pressure in conditions of hypertension. This first-in-man, proof-of-principle study tested the safety and feasibility of unilateral carotid body resection in 15 patients with drug-resistant hypertension. The procedure proved to be safe and feasible. Overall, no change in blood pressure was found. However, 8 patients showed significant reductions in ambulatory blood pressure coinciding with decreases in sympathetic activity. The carotid body may be a novel target for treating an identifiable subpopulation of humans with hypertension.

Impact of obesity on cardiovascular health.

This review examines the impact of obesity on cardiovascular health. We will review first, relationship between obesity and hypertension. Second, we will describe obesity-related subclinical abnormalities in cardiovascular function and structure. Third, we will summarize evidence linking obesity to overt cardiovascular disease including coronary artery disease, congestive heart failure, stroke, arrhythmias and sudden cardiac death. Fourth, we will discuss the potential mechanisms underlying increased cardiovascular risk in obese subjects. Last, we will discuss contribution of sleep apnea to the link between obesity and cardiovascular disease. Despite recent progress in understanding epidemiologic and pathophysiological links between obesity and cardiovascular disease, several issues remain to be addressed in the future studies. There is a clear need to identify better markers of obesity-related subclinical cardiovascular damage. Furthermore, we should improve identification of obese subjects at highest cardiovascular risk.

Relationship between heart rate variability, blood pressure and arterial wall properties during air and oxygen breathing in healthy subjects.

Previous studies reported that normobaric hyperoxia influences heart rate, arterial pressure, cardiac output and systemic vascular resistance, but the mechanisms underlying these changes are still not fully understood. Several factors are considered including degeneration of endothelium-derived nitric oxide by reactive oxygen species, the impact of oxygen-free radicals on tissues and alterations of autonomic nervous system function. Recently, new devices for the detailed non-invasive assessment of large and small arteries have been developed. Therefore, the aim of our study was to assess heart rate variability (HRV) as a potential indicator of autonomic balance and its relation to blood pressure and vascular properties during medical air (MAB) and 100% oxygen breathing (OXB) in healthy volunteers. In 12 healthy subjects we assessed heart rate and blood pressure variability, baroreflex sensitivity, respiratory frequency, common carotid artery diameter and its wall distensibility, as well as changes in the digital artery pulse waveform, stroke index and systemic vascular resistance during MAB and OXB. Mean and systolic blood pressure have increased significantly while digital pulse amplitude and carotid artery diameter were significantly lower during hyperoxia. Heart rate variability measures did not differ during MAB and OXB. However, the correlations between spectral HRV components and those hemodynamic parameters which have changed due to hyperoxia varied substantially during MAB (correlated significantly) and OXB (no significant correlations were noted). Our findings suggest that autonomic nervous system might not be the main mediator of the cardiovascular changes during 100% oxygen breathing in healthy subjects. It seems that the direct vascular responses are initial consequences of hyperoxia and other cardiovascular parameter alterations are secondary to them.

SCORE model underestimates cardiovascular risk in hypertensive patients: results of the Polish Hypertension Registry.

OBJECTIVE. The aim of the present study was to compare the effectiveness of Systemic COronary Risk Evaluation (SCORE) charts and European Society of Hypertension/European Society of Cardiology (ESH/ESC) hypertension guidelines for identifying high-risk hypertensive patients. METHODS. The data on hypertensive patients was collected using the Polish Hypertension Registry. We enrolled 636 patients (357 females and 279 males, mean age 54.4 (+/-) 7.9 years) from hypertension centres in Poland. RESULTS. Only 3.5% of the subjects had no additional risk factors. Thirty-six per cent of the patients had three or more risk factors. Metabolic syndrome was found in 40.1% of the patients. According to the SCORE charts, 9.0% of females and 27.2% of males had high to very high cardiovascular risk (p < 0.001). Taking into account risk factors and the metabolic syndrome, 55.7% of females and 56.3% of males (p = NS) had high or very high additional cardiovascular risk according to the 2007 ESH/ESC guidelines. For both females and males, the prevalence of high to very high risk was greater (p < 0.001) from the calculation based on the 2007 ESH/ESC guidelines than from the SCORE charts. Fifty-two per cent of patients classified as low to moderate risk according to the SCORE system, had high or very high risk according to the 2007 ESH/ESC guidelines. CONCLUSIONS. The SCORE charts seem to underestimate the burden of the cardiovascular risk among hypertensive patients. The cardiovascular risk, especially in the hypertensive female population, seems to be much higher when estimated according to the 2007 ESH/ESC guidelines.

Impact of abdominal obesity on the frequency of hypertension and cardiovascular disease in Poland - results from the IDEA study (international day for the evaluation of abdominal obesity).

INTRODUCTION: Cardiovascular disease (CVD) is a major cause of mortality, and has risk factors, which can be treated by lifestyle changes or medications. Abdominal obesity has been identified as the second strongest risk factor for myocardial infarction. OBJECTIVES: To assess the frequency of abdominal obesity and its relationship with hypertension (HT) and CVD in patients in Poland, and to compare frequencies of adiposity, HT and CVD between Poland and the North-West Europe Region, obtained in the IDEA study. METHODS: In Poland, general practitioners included 5371 patients, aged 18-80 years, eligible for analysis. Waist circumference (WC) was measured, and the presence of HT and CVD recorded. RESULTS: Increasing WC was significantly associated with HT and CVD, after adjustment for age (p<0.001). The frequency of abdominal obesity (WC >102/88 cm) was higher in Poland than in North-West Europe (36% vs 33% in men and 54% vs 45% in women, respectively, p<0.0001). Similarly, the frequency of HT in Poland was higher than in North-West Europe (47 vs 36% in men and 45 vs 30% in women, respectively p<0.001). In Poland CVD was 1.7-fold more frequent in men and 2.5-fold more frequent in women, compared with North-West Europe. CONCLUSION: In Polish adiposity, both WC and body mass index (BMI) were strongly related to HT and CVD. The frequency of abdominal obesity, obesity, HT and CVD in primary care patients is substantially higher in Poland than in North-West Europe.