Mortality of older persons with and without abnormalities in the physical examination of arterial system.

BACKGROUND: Ankle-brachial index (ABI) is a screening tool for peripheral arterial disease (PAD). However, persons with normal ABI may still exhibit abnormalities in the physical examination of arterial system (PHEA). OBJECTIVE: In older persons from the PolSenior study, we aimed to assess the risk of total mortality associated with abnormalities in PHEA in the context of dichotomised ABI. METHODS: We used data from the PolSenior survey and matched them with mortality information from the Polish Census Bureau. We obtained sociodemographic, medical history, and lifestyle data. The PHEA by a geriatrician included carotid, femoral, popliteal, posterior tibial and the dorsalis pedis arterial pulses, and auscultation of aorta, carotid, femoral, and renal arteries. Ankle-brachial index was tibial to brachial SBP ratio. We plotted the stratified Kaplan-Meier curves and used Cox's regression to assess the unadjusted and adjusted influence of PHEA result on time to death. RESULTS: The mean (standard deviation, SD) age of 852 persons (46.7% women) was 74.7 (10.6) years. In the ABI < 0.9 group, the PHEA was not associated with mortality. However, in the ABI ≥ 0.9 group, both in unadjusted and adjusted (RHR; 95% CI: 1.08; 1.02-1.16, p = 0.01) Cox regression, PHEA greater by 1 score was associated with mortality. Presence of 4 or more PHEA abnormalities was raising the risk in the ABI ≥ 0.9 group to the level associated with ABI < 0.9. CONCLUSIONS: In the older persons with normal ABI, the greater number of abnormalities during physical examination of arteries may be indicative of higher risk of death.

Breast cancer chemotherapy induces vascular dysfunction and hypertension through a NOX4-dependent mechanism.

Cardiovascular disease is the major cause of morbidity and mortality in breast cancer survivors. Chemotherapy contributes to this risk. We aimed to define the mechanisms of long-term vascular dysfunction caused by neoadjuvant chemotherapy (NACT) and identify novel therapeutic targets. We studied arteries from postmenopausal women who had undergone breast cancer treatment using docetaxel, doxorubicin, and cyclophosphamide (NACT) and from women with no history of such treatment matched for key clinical parameters. We explored mechanisms in WT and Nox4-/- mice and in human microvascular endothelial cells. Endothelium-dependent, NO-mediated vasodilatation was severely impaired in patients after NACT, while endothelium-independent responses remained normal. This was mimicked by a 24-hour exposure of arteries to NACT agents ex vivo. When applied individually, only docetaxel impaired endothelial function in human vessels. Mechanistic studies showed that NACT increased inhibitory eNOS phosphorylation of threonine 495 in a Rho-associated protein kinase-dependent (ROCK-dependent) manner and augmented vascular superoxide and hydrogen peroxide production and NADPH oxidase activity. Docetaxel increased expression of the NADPH oxidase NOX4 in endothelial and smooth muscle cells and NOX2 in the endothelium. A NOX4 increase in human arteries may be mediated epigenetically by diminished DNA methylation of the NOX4 promoter. Docetaxel induced endothelial dysfunction and hypertension in mice, and these were prevented in Nox4-/- mice and by pharmacological inhibition of Nox4 or Rock. Commonly used chemotherapeutic agents and, in particular, docetaxel alter vascular function by promoting the inhibitory phosphorylation of eNOS and enhancing ROS production by NADPH oxidases.

Disparate effects of ankle-brachial index on mortality in the 'very old' and 'younger old' populations-the PolSenior survey.

To assess the relationship between ankle-brachial index (ABI) and up to 10-year mortality in older individuals below and above the age of 80 years. In a multicenter survey of health status in the community dwelling subjects aged 55-59 and 65 + years in Poland, we assessed baseline medical history including risk-factors. We measured ABI, and serum creatinine, cholesterol, NT-proBNP, and interleukin-6 (IL-6) concentrations. We assessed mortality based on public registry. Between 2009 and 2019, 27.3% of 561 participants < 80 years, and 79.4% of 291 participants ≥ 80 years, died (p < 0.001); 67.8, 41.5, and 40.3% in the ABI groups < 0.9, 0.9-1.4, and > 1.4, respectively (p < 0.01). In the unadjusted Cox models, ABI was associated with mortality in the entire group, and < 80 years. In the entire group, analysis adjusted for age and sex showed mortality risk increased by 11% per year, and 50% with male sex. Mortality decreased by 37% per 1 unit ABI increase. In the group of people ≥ 80 years, only age was significantly associated with mortality (p < 0.001). In stepwise regression ABI < 0.9, male sex, active smoking, and NT-proBNP level were associated with risk of death < 80 years. In the ≥ 80 years old, mortality risk was associated with older age, and higher levels of IL-6, but not ABI. The ABI < 0.9 is associated with higher mortality in older people, but not among the oldest-old. In the oldest age group, age is the strongest predictor of death. In this age group, inflammageing is of importance.

Association of sulfur content in erythrocytes with cardiovascular parameters and blood pressure.

OBJECTIVE: The study aims at assessing the relationship between blood pressure, heart geometry parameters, and the erythrocyte content of sulfur, potassium, chlorine and phosphorus, in a group of patients with ambulatory systolic and diastolic blood pressure (SBP, DBP) below 140 or 90 mm Hg, respectively, who were otherwise healthy and untreated. METHODS: The study group consisted of 42 adults recruited in a primary care setting. The individuals were healthy, not undergoing any therapy and free from smoking. For each individual, data were obtained on: average 24-hour SBP and DBP, left ventricle geometry, complete blood count, lipids profile, fibrinogen, hs-CRP and the erythrocyte concentration of sulfur (S), potassium (K), chlorine (Cl) and phosphorus (P). RESULTS: Multivariate regression analysis showed statistically significant relationships of diastolic posterior wall thickness (PWTd) and relative wall thickness (RWT) with the concentration ratio of sulfur and potassium (S/K) in erythrocytes: PWTd and RWT increase as the S/K ratio increases. Also, SBP was found to be positively correlated with the S/K ratio. CONCLUSIONS: The increase in sulfur content in RBCs could be an indicator of the downregulation of nitric oxide (NO) erythrocyte bioavailability exerted by endogenously produced hydrogen sulfide (H2S), and, in consequence, a marker of the development of hypertension and/or adverse changes in heart geometry.

Insulin Resistance and Renal Sodium Handling Influence Arterial Stiffness in Hypertensive Patients with Prevailing Sodium Intake.

BACKGROUND: Insulin resistance and renal tubular sodium handling influence arterial structure and function and play an essential role in salt-sensitive forms of hypertension. METHODS: In a population with prevailing sodium consumption, we assessed the relationship between cardiovascular phenotypes (peripheral and central blood pressures, elastic properties of large arteries, the left ventricular structure) and sodium handling parameters (daily urinary sodium excretion, fractional urinary lithium excretion in proximal-FELi and distal tubules), as a function of insulin sensitivity-measured by homeostasis model assessment-insulin resistance (HOMA-IR), leptin-to-adiponectin (L/A) ratio, and homeostasis model assessment-adiponectin (HOMA-AD). RESULTS: In patients with FELi below the median value (corresponding to the group with increased proximal sodium reabsorption) and higher insulin resistance as measured by HOMA-IR, pulse wave augmentation indexes were significantly higher-AIxP (99.4% vs. 86.2%; P = 0.007), AIxC1 (159.4% vs. 144.2%; P = 0.04), and AIxC2 (36.1% vs. 28.3%; P = 0.02), than in patients with lower insulin resistance. The same trend was observed in relation to L/A ratio-AIxP (98.7% vs. 87.1%; P = 0.005), AIxC1 (158.6% vs. 144.5%; P = 0.02), and AIxC2 (35.6% vs. 28.5%; P = 0.01) and HOMA-AD-AIxP (99.7% vs. 83.8%; P = 0.001), AIxC1 (160.5% vs. 140.3%; P = 0.007), and AIxC2 (36.6% vs. 26.3%; P = 0.003). Such relationships were not observed in patients with FELi above the median value. CONCLUSIONS: In the hypertensive population with prevailing sodium intake, insulin resistance and increased sodium reabsorption in proximal tubules may affect arterial wall function.

Personality traits and hypertension-mediated organ damage. / Cechy osobowosci a powiklania narzadowe nadcisnienia tetniczego.

OBJECTIVES: Arterial hypertension may lead to the development of organ changes. This study compares different personality traits in hypertensive patients with and without left ventricular hypertrophy and arterial stiffness. METHODS: The study group consisted of 93 subjects (47 males and 46 females) with primary hypertension. Left ventricular mass index (LVMI) and pulse wave velocity (PWV) were evaluated and used as markers of cardiac and vascular damage. Personality traits of each patient were assessed using three psychometric tools: NEO-FFI, DS14 and EAS. RESULTS: Patients with increased PWV scored significantly lower than individuals with normal PWVin the following scales: NEO-FFI Neuroticism (18 vs. 27.5; p = 0.018), DS14 Negative affectivity (11.5 vs. 17; p = 0.035) and EAS Fear (10 vs. 13; p = 0.004). Subjects with left ventricular hypertrophy (increased LVMI values) presented lower levels of openness to experience (measured by the NEO-FFI) than persons with normal LVMI values (23 vs. 26; p = 0.027). CONCLUSIONS: These findings suggest that there are significant differences in personality traits between hypertensive patients with and without vascular and cardiac damage.

Clinical examination of peripheral arterial disease and ankle-brachial index in a nationwide cohort of older subjects: practical implications.

BACKGROUND: Prevalence of peripheral arterial disease increases with age and is related to increased morbidity and mortality. The clinical diagnosis includes the measurement of ankle-brachial index (ABI). AIMS: To check the prevalence of abnormal ABI, and the value of physical examination of arterial system in detection of ABI < 0.9. METHODS: We performed subgroup analysis of patients included in the PolSenior survey. We measured ABI, performed physical examination of arterial system, assessed laboratory and questionnaire factors related to atherosclerosis. Participants were divided according to ABI strata of < 0.9, 0.9-1.4 and > 1.4. Clinical score of abnormalities on physical examination was proposed. Using logistic regression, we obtained areas under the curve (AUC). RESULTS: The mean age of 844 participants (53.3% men) was 74.7 (10.6) years. ABI < 0.9 was found in 20.3% participants and it was linked to history of myocardial infarction, hypertension and renal failure. In the entire group, 72.4% of subjects declared, that they were able to walk a distance of 200 m without interruption. Higher clinical score was associated with lower ABI. Full physical examination (AUC = 0.67) followed by examination of lower extremities (AUC = 0.65) showed strongest diagnostic value for PAD based on ABI. Neither ABI nor clinical examination was a good predictor of the inability to walk 200 meters without difficulties. DISCUSSION/CONCLUSIONS: Full clinical examination, only moderately, adds to detection of PAD. The ability to walk 200 m is not a good measure of PAD in older subjects.

Should malnutrition risk be assessed in older patients with elevated levels of NT-proBNP?

Introduction An inverse relationship between natriuretic peptides (N­terminal fragment of the prohormone brain natriuretic peptide [NT­proBNP]) and body mass index (BMI) among healthy people and patients with chronic heart failure (CHF) was observed. Objectives The aim of the study was to assess the relationship between nutritional status and NT­proBNP concentrations in older persons. Patients and methods NT­proBNP concentrations, medical histories, and malnutrition risk using Mini Nutritional Assessment were evaluated. Body composition was measured with dual energy X­ray absorptiometry. The relationship of nutritional status with NT­proBNP concentrations (in tertiles) was assessed. Results The mean (SD) age of 106 participants was 72.16 (9.38) years. Heart failure was diagnosed in 72.6% of patients. The risk of malnutrition was recognized in 28.3%, and the percentage of patients at risk increased in subsequent NT­proBNP tertiles: from 16.7% in the first tertile to 48.6% in the third tertile (P = 0.005). The risk of malnutrition was associated with an increase in NT­proBNP concentrations per tertile (odds ratio [OR], 2.30; 95% CI, 1.30-4.07; P = 0.004). Based on a multivariable logistic model, the NT­proBNP concentration in the third tertile was associated with an over 9­fold higher risk of malnutrition (OR, 9.80; 95% CI, 2.00-48.17; P = 0.005) as compared with the lowest concentration. Among patients with CHF, the relationship between NT­proBNP and nutritional status was even stronger. Conclusions High NT­proBNP levels contribute to increased risk of malnutrition in older patients with heart failure. In patients with elevated NT­proBNP levels, the risk of malnutrition should be assessed.

Triglycerides as indicators of erythrocyte hemoglobin oxygen-binding properties1.

OBJECTIVES: To assess the relationships of clinical and laboratory parameters, with erythrocyte oxygen concentration. METHODS: The study group consisted of 47 healthy adults out of which 16 showed slightly higher blood pressure and were classified as individuals with prehypertension. For each individual, data were obtained on: systolic and diastolic blood pressure (SBP, DBP), blood morphology, lipids profile, fibrinogen, hs-CRP. The erythrocyte oxygen concentration was assessed with the Raman spectroscopy technique. Arithmetic means for all laboratory parameters were estimated by oxygen concentration tertiles and tested for statistical significance of linear trends across tertiles. RESULTS: The multivariate regression analysis showed statistically significant negative relationship of triglycerides level with oxygen concentration. CONCLUSIONS: A hypothesis has been formulated that triglycerides level is an indicator of the erythrocyte ability to transport oxygen to the tissues.

Blood pressure, arterial stiffness and endogenous lithium clearance in relation to AGTR1 A1166C and AGTR2 G1675A gene polymorphisms.

INTRODUCTION: Although recently a matter of epidemiologic controversy, sodium overload and its interaction with genetic factors predispose to hypertension and related target organ complications. METHODS: In 131 (66 male) treated hypertensives, we measured peripheral and central arterial pressures and pulse wave augmentation indexes (AIx(P), AIx(C1), AIx(C2)), pulse wave velocity (PWV), daily urinary sodium excretion and did genetic studies of AGTR1 A1166C and AGTR2 G1675A polymorphisms. Proximal (FE(Li)) and distal (FDR(Na)) sodium reabsorption measurements were performed using endogenous lithium clearance. RESULTS: In men, we found interaction between FDR(Na) and AGTR2 G1675A polymorphism with respect to AIx(C1) (p(INT)=0.01), AIx(C2) (p(INT)=0.05) and AIx(P) (p(INT)=0.006). Arterial stiffness increased with higher sodium reabsorption in the distal tubule, in the presence of AGTR2 G allele with the opposite tendency in A allele carriers. In the subgroup with FDR(Na) below median, as compared to those with FDR(Na) above median, the AIx(C1) (139.6±3.8 vs 159.1±5.7%; p=0.009), AIx(C2) (26.3±1.8 vs 33.3±1.7%; p=0.016) and AIx(P) (83.4±2.5 vs 96.5±2.6%; p<0.0001) were lower, in the G allele carrying men and GG homozygous women. CONCLUSIONS: The relation between sodium reabsorption in the distal tubule and the development of arterial stiffness depends on the AGTR2 G1675A polymorphism in blood pressure independent fashion.

Association of red blood cell distribution width, inflammation markers and morphological as well as rheological erythrocyte parameters with target organ damage in hypertension.

OBJECTIVES: To assess the relationships of red blood cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC) and erythrocyte deformability with pathological changes of selected target organs, and with inflammation markers interleukin-6 (IL-6) and fibrinogen, in a group of newly diagnosed, never-treated and otherwise healthy hypertensive patients. METHODS: The study group consisted of 101 adults divided into three sub-groups: 37 diagnosed arterial hypertension, 29 with hypercholesterolemia, and 35 healthy. The individuals with hypertension or hypercholesterolemia were otherwise healthy and were not on any therapy prior to entering the study. For each individual, data were obtained on: systolic and diastolic blood pressure (SBP, DBP), pulse wave velocity (PWV), carotid intima media thickness (IMT), left ventricle geometry, blood morphology, lipids profile, fibrinogen, CRP, IL-6 and red blood cell deformability index (DI). RESULTS: In the group of hypertensives, the multivariate regression analysis showed significant relationship of RDW with PWV, IL6 and fibrinogen. Also, RDW was found to be correlated with MCHC and DI, and MCHC was significantly related to IMT and IL-6. CONCLUSIONS: A hypothesis has been formulated that the development of target organ damage in hypertension is accompanied by the increasing impairment of erythropoiesis. This process may be mediated by inflammation.

Successful treatment of digital tip necrosis in rheumatoid vasculitis with anti-CD20 antibody rituximab.

We report a successful treatment with rituximab in the case of rheumatoid vasculitis causing digital tips necrosis in exacerbated rheumatoid arthritis. The vasculitis lesions did not respond completely to intravenous methylprednisolone and cyclophosphamide but responded on rituximab treatment. Deep necrosis of a digital tip resolved entirely after completing a course of rituximab.

Skin microcirculation and echocardiographic and biochemical indices of left ventricular dysfunction in non-diabetic patients with heart failure.

BACKGROUND: We sought to noninvasively investigate skin microcirculation and to assess the relation between parameters of microcirculation and echocardiographic and biochemical parameters of left ventricular (LV) function in non-diabetic patients with heart failure (HF). METHODS AND RESULTS: We measured skin microcirculation with laser Doppler flowmetry (LDF) at basal conditions (MFb), after warming to 44 degrees Centigrade (MF44) and after occlusion (AUC, PF%). Blood was sampled for NT-proBNP. We obtained information on patients' medical history and medication status. The mean (SD) age of 100 patients (43 women) was 68.2 ± 11.5 years. LV ejection fraction (LVEF) averaged 34.9 ± 13.3%, LV end-diastolic diameter (LVEDD) 6.0 ± 0.9 cm, NT-proBNP 4,582.6 ± 6,339.7 pg/mL. The parameters of microcirculation averaged: MFb 6.2 ± 4.7 perfusion units (PU), PF% 716.0 ± 437.8%, AUC 794 ± 706.1 PU/s, and MF44 77.9 ± 40.2 PU. NT-proBNP correlated negatively with LVEF (p ≤ 0.0001) and positively with LVEDD (p = 0.003). MFb was positively correlated with LVEF (r = 0.24, p = 0.03), and MF44 was negatively correlated with LVEDD (r = 0.22, p = 0.02). The relations remained significant after adjustments for sex, age, and use of medication. We observed no relation between NT-proBNP and microcirculatory derangement. CONCLUSIONS: LDF-derived parameters of skin microcirculation are related to echocardiographic, but not biochemical, indices of HF.

[Use of vasopressin analogues and antagonist in clinical practice]. / Wspólczesne zastosowanie wazopresyny, jej agonistów i antagonistów.

Vasopressin is an endogenous peptide hormone with the antidiuretic and vasoactive action. Its mechanisms of action on vasal smooth muscles and kidney collective tubules are well known. This hormone also plays a role in the central nervous system and influences smooth muscles of the gastrointestinal tract. The recent research results indicated much more extensive effects of endogenous vasopressin action on the circulation than appeared from the water-electrolyte balance regulation only. The use of this hormone is actually an alternative for catecholamine in treatment of the shock. This paper presents short review of vasopressin action, actual clinical use and perspectives in use of vasopressin antagonists in the heart failure.

[Angiosarcoma (hemangiosarcoma) cordis]. / Naczyniakomiesak krwionosny serca.

The case of a young 32 year old male with a primary cardiac angiosarcoma is reported. The neoplasm manifested itself by a quickly increasing cardiac tamponade but without metastases. The nonradical resection of the tumor was made because of local invasion with tumor tissue. The patient was followed-up for 3 years after the surgery and no recurrence of the malignant process was observed. Cardiac angiosarcoma is a very rare malignant tumor of soft tissues. In spite of significant progress in clinical treatment, for a patient diagnosed antemortem with cardiac angiosarcoma, the long-term expectations are usually very poor. Commonly known risk factors for this group of neoplasms (haemangioma of skin, chroniclymphedema, chronic post-tuberculosis pleurisy, X-ray, thorium dioxide) cannot be easily associated with the primary cardiac angiosarcoma cases. The search for chromosomal anomalies and gene mutations leading to cardiac angiosarcoma is ongoing. There is hope that recently obtained evidence for mutation of the p53gen, will provide a better understanding of this heart neoplasia.