natriuretic-peptide--brain and Vascular-Diseases

Nocturnal polyuria (NP), the most common etiology of nocturia, can be caused by various medical conditions, including cardiovascular disease, obstructive sleep apnea, renal tubular dysfunction, as well as medications (eg, diuretics) and/or behavioral patterns. NP in the absence of underlying medical conditions has been described as NP syndrome and is thought be the result of impaired circadian release of endogenous arginine vasopressin. Desmopressin, a synthetic arginine vasopressin analog, has been shown to be an effective replacement therapy in adults with nocturia due to NP. Further studies on the subset of patients with NP syndrome are warranted to maximize benefit from antidiuretic treatment. In addition, a connection between the pathophysiological mechanisms underlying NP and essential hypertension has been suggested, and hypertension has been shown to be a significant risk factor for nocturia, while an association between NP and brain natriuretic peptide levels has also been reported in patients with nocturia. Hypertension is now viewed as a disorder of blood vessels and treatment is directed at the vasculature rather than the blood pressure, with the latter currently serving as a biomarker for arterial injury. Nocturia is thought to be associated with the beginning of this cardiovascular continuum as studies have reported a link between coronary heart disease and nocturia. Therefore, there is an increasing need to elucidate the complex mechanisms implicated in the association between nocturia and hypertension to promote the development of more individualized therapies for the treatment of nocturia.

Topics: Forecasting; Humans; Hypertension; Natriuretic Peptide, Brain; Nocturia; Polyuria; Prevalence; Vascular Diseases; Vascular Stiffness

B-type natriuretic peptide (also known as brain natriuretic peptide or BNP) is a physiologic marker that is often used to assess a patient's global cardiovascular health. BNP is secreted from the ventricular cardiac myocytes in response to stretch that occurs due to increased intravascular volume. PreproBNP is cleaved into BNP and N-terminal proBNP (NT proBNP) to cause diuresis, natriuresis, and vasodilation, and can be measured with a blood laboratory assay test or point-of-care testing. BNP/NT proBNP has been most extensively studied in the diagnosis and management of heart failure, but within the past 5 years, interest has carried over to vascular surgery patients. Studies have demonstrated that elevated levels of BNP/NT-proBNP (typically >100 pg/mL/>300 pg/mL) are associated with major adverse cardiac events at 30 and 180 days. Additional analysis of BNP/NT-proBNP has demonstrated that patients can be classified as very low risk (<19 pg/mL), low risk (<100 pg/mL), intermediate risk (100 to 400 pg/mL), or high risk (>400 pg/mL). BNP/NT-proBNP in the low- and very-low-risk groups suggests patients are unlikely to have a major adverse cardiac event. An elevated BNP/NT-proBNP, excluding those with reasons for abnormal values, suggests the need for additional risk stratification and medical risk factor optimization. A preoperative measure of BNP or NT-proBNP affords an easy and rapid opportunity to individually and objectively quantify perioperative cardiovascular risk. Recent studies have also identified other biomarkers, none superior to BNP or NT-proBNP, but that, when used concomitantly, aid in further stratifying perioperative risk and will likely be the focus of future investigations.

Topics: Biomarkers; Humans; Natriuretic Peptide, Brain; Patient Selection; Peptide Fragments; Predictive Value of Tests; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome; Up-Regulation; Vascular Diseases; Vascular Surgical Procedures

Vitamin K insufficiency is common and linked to an increased risk of cardiovascular disease and osteoporotic fractures. The aim of this study was to examine whether daily supplementation with oral vitamin K could improve vascular health and physical function in older people with established vascular disease.. A double blind, randomised, placebo-controlled trial. Participants aged ≤ 70 years with a history of vascular disease were randomised to receive 6 months of daily oral 100mcg vitamin K2 (MK7 subtype) or matching placebo with outcomes measured at 0, 3 and 6 months. The primary outcome was between-group difference in endothelial function assessed using flow-mediated dilatation of the brachial artery at 6 months. Secondary outcomes included carotid-radial pulse wave velocity, augmentation index, blood pressure, carotid intima-media thickness, C-reactive protein, B-type natriuretic peptide, cholesterol and desphospho-uncarboxylated matrix Gla protein levels. Handgrip strength and the Short Physical Performance Battery assessed physical function, while postural sway was measured using a 3-dimensional force platform.. 80 participants were randomised, mean age 77 (SD 5) years; 44/80 were male. Vitamin K levels rose in the intervention arm compared to placebo (+48 pg/ml vs -6 pg/ml, p=0.03) at 6 months. Desphospho-uncarboxylated Matrix Gla protein levels fell in the intervention group compared to placebo at 6 months (-130 [SD 117] pmol/L vs +13 [SD 180] pmol/L, p<0.001). No change was seen in endothelial function (between group difference -0.3% [95%CI -1.3 to 0.8], p=0.62). A modest, non-significant improvement in pulse wave velocity was seen in the vitamin K group (-0.8m/s [95%CI -1.8 to 0.3], p=0.15) while all other vascular and physical function outcomes unchanged.. Six months of vitamin K2 supplementation did not improve markers of vascular health or physical function in older patients with vascular disease.

Topics: Aged; Biomarkers; Blood Pressure; Brachial Artery; C-Reactive Protein; Carotid Intima-Media Thickness; Cholesterol; Dietary Supplements; Double-Blind Method; Female; Hand Strength; Humans; Male; Natriuretic Peptide, Brain; Pulse Wave Analysis; Treatment Failure; Vascular Diseases; Vitamin K

Inflammation, coagulation activation, endothelial dysfunction and subclinical vascular disease are cross-sectionally associated with frailty. Cardiac-specific biomarkers are less-well characterised. We assessed associations between these and frailty, in men with, and without, cardiovascular disease (CVD).. Cross-sectional analysis of 1096 men without, and 303 with, CVD, aged 71-92, from the British Regional Heart Study. Multinominal logistic regression was performed to examine the associations between frailty status (robust/pre-frail/frail) and, separately, C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), D-dimer, von Willebrand factor (vWF), high-sensitivity cardiac troponin-T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) (all natural log-transformed), and, in men without CVD, carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), adjusted for age, renal function, BMI, social class, smoking, polypharmacy, cognition, multimorbidity and systolic blood pressure. Explanatory variables with p < 0.05 were carried forward into mutually-adjusted analysis.. In men without CVD, higher CRP, IL-6, vWF, tPA, hs-cTnT, NT-proBNP, cfPWV, and lower DC were significantly associated with frailty; mutually-adjusted, log IL-6 (OR for frailty = 2.02, 95%CI 1.38-2.95), log hs-cTnT (OR = 1.95, 95%CI 1.24-3.05) and DC (OR = 0.92, 95%CI 0.86-0.99) retained associations. In men with CVD, higher CRP, IL-6, and hs-cTnT, but not vWF, tPA, NT-proBNP or D-dimer, were significantly associated with frailty; mutually-adjusted, log hs-cTnT (OR 3.82, 95%CI 1.84-7.95) retained a significant association.. In older men, biomarkers of myocardial injury are associated with frailty. Inflammation is associated with frailty in men without CVD. Carotid artery stiffness is associated with frailty in men without CVD, independently of these biomarkers.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Frailty; Humans; Inflammation; Interleukin-6; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pulse Wave Analysis; Risk Factors; Tissue Plasminogen Activator; Troponin T; Vascular Diseases; von Willebrand Factor

The Canadian Cardiovascular Society 2016 guidelines recommend pre-operative measurement of brain natriuretic peptide (BNP) to risk-stratify patients for a 30-day composite outcome of death, myocardial infarction, or asymptomatic myocardial injury after noncardiac surgery (MINS). Whether this practice affects outcomes is unclear. The aim of this study was to examine the clinical utility of brain natriuretic peptide and myocardial injury after noncardiac surgery.. Analysis of a prospectively maintained database identified all elective open vascular surgery cases at an academic teaching hospital from January 2015 to December 2018. Pre-operative BNP values were available from June 2018 onward after becoming institutionally mandated. Co-morbidities were also collected to stratify patients using the Revised Cardiac Risk Index. The composite outcome of 30-day mortality, myocardial infarction, or MINS was determined.. Prior to BNP becoming an institutionally required test, data was available from 1176 open cases. The 30-day mortality was 1.3% (15/1176) and post-operative myocardial infarction rate was 2.3% (27/1176). BNP measurements were collected in 91 consecutive patients. Ten patients (11%) experienced the composite outcome of mortality, myocardial infarction, or MINS. Elevated BNP was associated with increased odds of the composite outcome (P = 0.04), but not with mortality or myocardial infarction. Revised Cardiac Risk Index score was not predictive of outcomes. The majority of patients who qualified for the composite outcome experienced only an asymptomatic troponin rise (80%). Two patients met the universal definition of myocardial infarction, one of whom died. No other deaths occurred within 30 days. Detection of MINS did not result in any significant changes to patient management.. Elevated BNP correlates with increased MINS. An asymptomatic troponin rise is the most commonly observed event, with unclear clinical implications. BNP may over-estimate surgical risk. Further studies on the long-term outcomes of patients with elevated BNP and MINS are required before widely adopting this strategy in vascular surgery patients.

Topics: Aged; Biomarkers; Female; Heart Injuries; Humans; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Troponin; Vascular Diseases; Vascular Surgical Procedures

Chronic rejection induces the occurrence of orthotopic allograft transplantation (OAT) vasculopathy, which results in failure of the donor organ. Numerous studies have demonstrated that in addition to regulating blood sugar homeostasis, dipeptidyl peptidase-4 (DPP-4) inhibitors can also provide efficacious therapeutic and protective effects against cardiovascular diseases. However, their effects on OAT-induced vasculopathy remain unknown. Thus, the aim of this study was to investigate the direct effects of sitagliptin on OAT vasculopathy in vivo and in vitro.. The PVG/Seac rat thoracic aorta graft to ACI/NKyo rat abdominal aorta model was used to explore the effects of sitagliptin on vasculopathy. Human endothelial progenitor cells (EPCs) were used to investigate the possible underlying mechanisms.. We demonstrated that sitagliptin decreases vasculopathy in OAT ACI/NKyo rats. Treatment with sitagliptin decreased BNP and HMGB1 levels, increased GLP-1 activity and stromal cell-derived factor 1α (SDF-1α) expression, elevated the number of circulating EPCs, and improved the differentiation possibility of mononuclear cells to EPCs ex vivo. However, in vitro studies showed that recombinant B-type natriuretic peptide (BNP) and high mobility group box 1 (HMGB1) impaired EPC function, whereas these phenomena were reversed by glucagon-like peptide 1 (GLP-1) receptor agonist treatment.. We suggest that the mechanisms underlying sitagliptin-mediated inhibition of OAT vasculopathy probably occur through a direct increase in GLP-1 activity. In addition to the GLP-1-dependent pathway, sitagliptin may regulate SDF-1α levels and EPC function to reduce OAT-induced vascular injury. This study may provide new prevention and treatment strategies for DPP-4 inhibitors in chronic rejection-induced vasculopathy.

Topics: Animals; Aorta, Thoracic; Chemokine CXCL12; Dipeptidyl-Peptidase IV Inhibitors; Endothelial Progenitor Cells; Glucagon-Like Peptide 1; HMGB1 Protein; Hypoglycemic Agents; Male; Natriuretic Peptide, Brain; Rats; Rats, Inbred ACI; Sitagliptin Phosphate; Transplantation, Homologous; Vascular Diseases

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac dysfunction and has been linked to various indices of large vessel disease. However, it remains unclear whether NT-proBNP also relates to microvascular damage. In a community-dwelling population, we studied the association between NT-proBNP and retinal microvascular damage.. From the population-based Rotterdam Study, we included 8437 participants (mean age 64.1 years and 59% women) without a history of cardiovascular disease, with NT-proBNP data and gradable retinal images. NT-proBNP serum levels were measured using an immunoassay. Retinopathy signs, that is, exudates, microaneurysms, cotton wool spots, and dot/blot hemorrhages, present on fundus photographs were graded in the total study population; retinal vascular calibers, that is, arteriolar and venular calibers, were semiautomatically measured in a subsample (n=2763) of the study population. We conducted cross-sectional analyses on the association between NT-proBNP and retinal microvascular damage using logistic and linear regression models, adjusting for age, sex, and cardiovascular risk factors. We found that NT-proBNP was associated with the presence of retinopathy (adjusted odds ratio [95% confidence interval] per SD increase in natural log-transformed NT-proBNP: 1.14 [1.03-1.27]). We also found that higher NT-proBNP was associated with narrower arteriolar calibers (adjusted mean difference in arteriolar caliber per SD increase in natural log-transformed NT-proBNP: -0.89 µm [-1.54 to -0.24]). This association remained unchanged after excluding participants with retinopathy signs.. In participants free of clinical cardiovascular disease, higher levels of NT-proBNP are associated with retinal microvascular damage, suggesting a potential role for NT-proBNP as marker for small vessel disease.

Topics: Aged; Arterioles; Biomarkers; Cross-Sectional Studies; Female; Humans; Immunoassay; Linear Models; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Odds Ratio; Peptide Fragments; Photography; Predictive Value of Tests; Retinal Diseases; Risk Assessment; Risk Factors; Up-Regulation; Vascular Diseases; Venules

Identification of patients at high risk for perioperative cardiac events (POCE) is clinically important. This study aimed to determine whether preoperative measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict POCE, and compared its predictive value with that of conventional cardiac risk factors and stress thallium scans in patients undergoing vascular surgery.. Patients scheduled for non-cardiac vascular surgery were prospectively enrolled. Clinical risk factors were identified, and NT-proBNP levels and stress thallium scans were obtained. POCE was the composite of acute myocardial infarction, congestive heart failure including acute pulmonary edema, and primary cardiac death within 5 days after surgery. A modified Revised Cardiac Risk Index (RCRI) was proposed and compared with NT-proBNP; a positive result for ischemia and a significant perfusion defect (≥ 3 walls, moderate to severely decreased, reversible perfusion defect) on the thallium scan were added to the RCRI.. A total of 365 patients (91% males) with a mean age of 67 years had a median NT-proBNP level of 105.1 pg/mL (range of quartile, 50.9 to 301.9). POCE occurred in 49 (13.4%) patients. After adjustment for confounders, an NT-proBNP level of > 302 pg/mL (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.1 to 10.3; p < 0.001) and a high risk by the modified RCRI (OR, 3.9; 95% CI, 1.6 to 9.3; p = 0.002) were independent predictors for POCE. Comparison of the area under the curves for predicting POCE showed no statistical differences between NT-proBNP and RCRI.. Preoperative measurement of NT-proBNP provides information useful for prediction of POCE as a single parameter in high-risk patients undergoing noncardiac vascular surgery.

Topics: Aged; Biomarkers; Chi-Square Distribution; Elective Surgical Procedures; Female; Heart Diseases; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Preoperative Period; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Sensitivity and Specificity; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Vascular Diseases; Vascular Surgical Procedures

High PTH levels have been reported in patients with chronic heart failure (CHF). Similarly, its levels increase with aging and are related to impaired survival in elderly adults. However, its relationship with neuroendocrine activation and endothelial dysfunction in CHF has not been previously studied. Seventy-three CHF males with New York Heart Association (NYHA) classes II and III and 20 control subjects aged ≥ 55 yr were recruited. PTH, 25-hydroxyvitamin D [25(OH)D], N-terminal pro-brain natriuretic peptide (NT-pro-BNP), adiponectin, and osteoprotegerin were measured. Endothelial function (brachial flow mediated dilation), echocardiography, physical performance, and quality of life were assessed, as well. CHF patients had markedly increased serum PTH (77 ± 33 vs 40 ± 11 pg/ml, p<0.0001), NT-pro-BNP [1809 (2742) vs 67 (74) pg/ml, p<0.0001], adiponectin (17 ± 9 vs 10 ± 2 μg/ml, p<0.0001), osteoprotegerin, whereas 25(OH)D levels were decreased compared to controls. Increased PTH is positively correlated with NTpro- BNP (r=0.399, p<0.0001), adiponectin (r=0.398, p<0.0001), and osteoprotegerin, whereas negatively with 25(OH)D in CHF patients. Additionally, increased serum PTH was associated with endothelial dysfunction, echocardiographic variables of heart failure progression, impaired physical performance, and deteriorated quality of life. In a multivariate linear regression analysis, increased serum PTH was independently associated with neuroendocrine activation (NT-pro-BNP, adiponectin) and endothelial dysfunction in elderly CHF men (R2=0.455). Additionally, demonstrated relations with other well-established variables of heart failure severity suggest the potential role of serum PTH in the pathogenesis and non-invasive monitoring of heart failure progression. Future studies are needed to evaluate the predictive value of serum PTH for clinical outcomes as well as beneficial potential of PTH suppression in CHF patients.

Topics: Adiponectin; Aged; Chronic Disease; Endothelium, Vascular; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurosecretory Systems; Osteoprotegerin; Parathyroid Hormone; Peptide Fragments; ROC Curve; Vascular Diseases; Vitamin D

Recent interest has focussed on the role of biomarkers to predict outcome in patients undergoing major vascular surgery. We wished to determine if pre- and postoperative N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels could predict all-cause mortality (ACM; primary aim) and major adverse cardiac event (MACE) (secondary aim) in the medium-term follow-up in patients who have undergone elective major vascular surgery.. Patients who underwent major elective vascular surgery (n = 136) were followed up for up to 2 years. ACM and first MACE episode were identified from the case notes and the patient management system database of the hospital intranet.. One patient was lost to follow-up. In the mean follow-up of 654 days, 27 (20%) died and 23 (17%) patients suffered a MACE. Receiver operator curve (ROC) analysis showed that a pre-operative NT-pro-BNP level with a cut-off of 359 pg ml(-1) had a sensitivity and specificity of 73% each (area under the curve (AUC) 80%, p < 0.001) in predicting ACM and sensitivity of 74% and specificity of 71% (AUC 75%, p < 0.001) to detect a MACE. The overall 2-year survival rate was 84%, 93% in the <359 pg ml(-1) group and 68% in the ≥359 pg ml(-1) group (p < 0.001). Following multivariate analysis, pre-operative NT-pro-BNP at a value of ≥359 pg ml(-1) remained an independent predictor of ACM (odds ratio 3.6 (confidence interval (CI): 1.6-8.1), p = 0.002) Postoperative NT-pro-BNP was a predictor of mortality but not a MACE.. This study has shown that pre-operative NT-pro-BNP is an independent predictor of ACM and MACE on medium-term follow-up.

Topics: Aged; Aged, 80 and over; Biomarkers; Cause of Death; Female; Follow-Up Studies; Heart Diseases; Humans; Immunoenzyme Techniques; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; ROC Curve; Survival Rate; Time Factors; United Kingdom; Vascular Diseases; Vascular Surgical Procedures

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).. 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.. LDF-derived parameters of skin microcirculation are related to echocardiographic, but not biochemical, indices of HF.

Topics: Adrenergic beta-Antagonists; Aged; Biomarkers; Echocardiography; Female; Heart Failure; Humans; Laser-Doppler Flowmetry; Male; Microcirculation; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Skin; Stroke Volume; Vascular Diseases; Ventricular Dysfunction, Left

Re-stenosis or remodeling of coronary and peripheral arteries remains a major complication following balloon-angioplasty or stenting. This study was designed to investigate the effect of nesiritide, a recombinant B-type natriuretic peptide (BNP), on vascular remodeling following balloon-induced endothelial injuries. Twenty-eight male New Zealand rabbits were divided into nesiritide-treated (0.1 mg/kg/day, sc, for 4 weeks, n = 10), saline-treated control (n = 10) and sham-operated groups (n = 8). In the nesiritide and control groups, a balloon catheter was inserted to the right iliac artery to induce injuries. Vascular endothelial growth factor (VEGF) was measured by immunohistochemistry. The area under internal elastic membrane of the arterial wall (643.2 ± 134.1 vs 493.7 ± 139.3 µm(2), p < 0.05) and the area under external elastic membrane (1495.1 ± 204.9 vs 1265.9 ± 232.6 µm(2), p < 0.05) in the nesiritide group were greater than those in the control group, but were smaller than those in the sham-operated group (p < 0.05). The stenosis ratio was lower in the nesiritide group than in the control group (18.7 ± 7.7% vs 38.0 ± 8.3%, p < 0.01). Importantly, the VEGF expression rate was significantly lower in the nesiritide group than in the control group (42.2 ± 8.8% vs 56.1 ± 13.1%, p < 0.05), while there were no signs of VEGF expression in the non-injured arteries of the three groups. In conclusion, nesiritide treatment reduces the stenosis of the rabbit iliac artery following balloon-induced endothelial injuries probably by decreasing VEGF expression.

Topics: Angioplasty, Balloon; Animals; Blood Vessels; Constriction, Pathologic; Drug Evaluation, Preclinical; Endothelium, Vascular; Iliac Artery; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Rabbits; Recombinant Proteins; Vascular Diseases; Vascular Endothelial Growth Factor A

Decreased vitamin D serum levels have been recently related to arterial stiffening and vascular calcifications in haemodialysis (HD) patients, but the pathophysiology of this association is not yet clear. The aim of this study was to evaluate the relationship between vascular calcifications, cardiovascular risk factors [including brain natriuretic peptide (BNP), pulse pressure (PP) and left ventricular mass index] and 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D3] serum levels.. We performed a cross-sectional study with 223 prevalent HD patients, 48% females, 27% diabetics, with the mean age of 62.7 +/- 15.3 years and the mean HD time of 42.9 +/- 39.3 months. Forty-seven percent of the patients were taking active forms of vitamin D.. Serum levels of [25(OH)D3] were low (21.6 +/- 12.2 ng/mL) and negatively correlated with age (r = -0.31, P < 0.001), diabetes mellitus (DM) (r = -0.20, P = 0.004), C-reactive protein (r = -0.25, P < 0.001), log(10) BNP (r = -0.22, P = 0.002), PP > 65 mmHg (r = -0.21, P = 0.003) and vascular calcifications (r = -0.26, P < 0.001). Levels of [25(OH)D3] were positively correlated with [1,25(OH)(2)D3] (r = 0.25, P < 0.001) and albumin (r = 0.23, P = 0.001). On multivariate analysis, levels of [25(OH)D3] were independently associated with DM (P < 0.001), lower albumin levels (P = 0.003), higher BNP values (P = 0.005), PP > 65 mmHg (P = 0.006) and a higher vascular calcification score (>or= 3) (P = 0.002).. These results suggest that lower levels of [25(OH)D3] are a cardiovascular risk marker in HD patients, since they are strongly associated with higher BNP levels, increased PP and with the presence of vascular calcifications. The exact role of [25(OH)D3] deficiency on cardiovascular morbi-mortality needs to be clarified in large randomized controlled trials.

Topics: Aged; Calcifediol; Calcinosis; Calcitriol; Cardiovascular Diseases; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Risk Factors; Vascular Diseases; Vitamin D Deficiency

There is increasing evidence that vascular disease contributes to cognitive impairment and dementia. Clarification of the role of vascular risk factors in dementia is important because most are modifiable, in contrast to other risk factors such as age and genetics.. In 451 patients with mental illness we have investigated three biochemical markers related to vascular disease, total plasma homocysteine (tHcy), cystatin C, and N-terminal-pro brain natriuretic peptide (NT-proBNP), and their association with vascular disease, diagnoses, and brain imaging findings (CT).. Plasma tHcy, serum cystatin C, and serum NT-proBNP showed significantly increased frequencies of elevated levels in patients with vascular disease, in patients with a pathological CT finding indicating cerebrovascular disease, and in patients above 75 years of age.. It is possible that the control of conventional vascular risk factors and therapy could be guided by the level of plasma tHcy, serum cystatin C, and serum NT-proBNP. Patients with an elevation of any of these three parameters could be selected for a lower target level of risk factors such as blood pressure, hyperlipidemia etc. than conventional target levels.

Topics: Aged; Aged, 80 and over; Brain; Cystatin C; Cystatins; Dementia; Depression; Female; Humans; Hyperhomocysteinemia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Tomography, X-Ray Computed; Vascular Diseases

Topics: Animals; Atrial Natriuretic Factor; Cardiac Output; Head-Down Tilt; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Vascular Diseases; Vascular Resistance; Vasoconstriction; Veins; Weightlessness Simulation

The purpose of this work was to assess the prognostic role of glomerular filtration rate (GFR) and NT-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality end points in the vascular population.. The GFR and NT-proBNP have been shown to predict mortality end points in free-living and limited vascular populations, independent of traditional risk factors. However, their prognostic power in an unrestricted vascular population is poorly understood.. A total of 412 subjects from a vascular cohort with a history of either peripheral arterial disease (PAD) and/or other cardiovascular disease (CVD) were included in this prospective cohort analysis and followed for an average of 6.7 years. Outcome variables were all-cause mortality, ischemic heart disease (IHD) mortality, and any cardiovascular mortality. The prognostic roles of GFR and NT-proBNP levels were determined using multivariate survival analysis.. Higher GFR (per 10 ml/min/1.73 m2) was significantly protective for all-cause mortality (hazard ratio [HR] 0.81, p < 0.001), IHD mortality (HR 0.82, p = 0.008), and CVD mortality (HR 0.84, p = 0.005). Conversely, NT-proBNP was not a significant predictor of any mortality end point. The GFR showed the strongest association in subjects with a history of other CVD. Although NT-proBNP did not demonstrate a significant prognostic role in any of the subgroups, the data were suggestive for patients with PAD alone.. Glomerular filtration rate was a robust predictor of all-cause, IHD, and cardiovascular mortality in the vascular population, particularly in those with a history of other CVD, while NT-proBNP showed a suggestive association limited to the group with PAD only. These findings suggest that these markers must be selectively applied in the vascular population for greatest clinical utility.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Cohort Studies; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Survival Rate; Vascular Diseases

There is a high frequency of elevated plasma total homocysteine (tHcy) concentrations in elderly patients with mental disorders. Psychogeriatric patients with a history of vascular disease exhibit a significantly higher plasma tHcy concentration than patients without vascular disease.. The main reason for the present study is to further investigate the association between plasma tHcy concentration and vascular disease in psychogeriatric patients. We therefore investigated 152 psychogeriatric patients and determined plasma tHcy and its most important determinants (serum folate and serum cobalamin, serum cystatin C and serum creatinine). The patients were divided into two groups according to the presence of vascular disease. Eighty-seven patients had concomitant vascular disease. We also analysed the natriuretic peptide N-terminal pro brain natriuretic peptide (NT-proBNP) and protein S-100B in serum. NT-proBNP is a marker for congestive heart failure, whereas protein S-100B is a marker for brain damage.. The plasma tHcy concentration is elevated in the presence of dementia or vascular disease in psychogeriatric patients. The presence of dementia or vascular disease is also associated with higher age, renal impairment and lower serum folate concentration than in patients without dementia or vascular disease. Furthermore, we observed elevated serum concentrations of NT-proBNP in patients with dementia or vascular disease as a sign of poorer cardiovascular status. Likewise, protein S-100B concentrations were elevated in patients with dementia or vascular disease, possibly indicating brain damage in these groups of patients.. The high frequency of comorbidity of vascular disease and mental illness indicates a possibility to prevent and treat psychogeriatric disease by actively counteracting vascular disease in patients with psychogeriatric symptoms. Routine determination of NT-proBNP is valuable for obtaining information about cardiovascular status.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Creatinine; Cystatin C; Cystatins; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein S; Vascular Diseases; Vitamin B 12

Increased levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP) are associated with left ventricular dysfunction (LVD) and left ventricular hypertrophy (LVH), but the relation of NT-proBNP to ambulatory blood pressure (ABP) and hypertensive target organ damage in high-risk patients with peripheral arterial disease (PAD) has not been studied. We hypothesized that NT-proBNP levels were increased in patients with PAD in comparison to a matched control group and that levels of NT-proBNP were related to ABP.. Blood samples were analysed for NT-proBNP in 103 males with PAD and 96 age- and sex-matched controls. Ninety-eight PAD patients performed ABP monitoring and 99 underwent Tc-99m Sestamibi myocardial perfusion SPECT.. NT-proBNP was significantly increased in PAD patients compared with controls [median (interquartiles)] 167(76, 418) vs 68(38, 142) pg/ml, p<0.001. Plasma levels of NT-proBNP correlated positively to systolic blood pressure (SBP), pulse pressure (PP), night-day ratio of SBP and showed the strongest correlation to average night PP (r=0.42, p<0.001). In multiple regression analysis, night PP remained independently related to NT-proBNP.. NT-proBNP levels are markedly increased in PAD patients compared to age-matched controls. Night PP is related to NT-proBNP levels independently of other variables highlighting the importance of ambulatory PP as a cardiovascular risk factor. Measurement of NT-proBNP could be indicated in PAD patients for further risk stratification.

Topics: Aged; Arteries; Blood Pressure; Electrocardiography; Female; Heart; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Vascular Diseases

Primary prevention of cardiovascular disease has been aimed at risk factor identification and treatment without efforts to document early cardiovascular disease. The objective of the current study is to screen individuals with vascular and cardiac tests aimed at identifying early abnormalities likely to progress and to measure risk contributors susceptible to therapy.. A center was established for comprehensive screening of an asymptomatic population with 10 tests designed to detect early vascular and cardiac abnormalities and blood tests to identify potential targets for risk contributor intervention. The first 396 individuals screened in the center have been analyzed.. Using a scoring system from 0 (no disease) to 20 (advanced disease), 49% of the population exhibited scores of > or =5 and 39% exhibited scores of > or =6. These scores appear indicative of early disease mandating initiation of or change in medical therapy, which was recommended to the individuals screened and to their primary care physicians.. The screening tests utilized are effective in uncovering unsuspected early cardiovascular disease in which targeted treatment could be effective in reducing the incidence of cardiovascular events in susceptible individuals. Documentation of the sensitivity and specificity of this approach requires longitudinal study.

Topics: Adult; Aged; Arteries; Atrial Natriuretic Factor; Biomarkers; Blood Pressure Determination; Echocardiography; Elasticity; Electrocardiography; Female; Fundus Oculi; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Sex Factors; Systole; Vascular Diseases; Ventricular Dysfunction, Left

Lysophosphatidylcholine (LPC), a major atherogenic lysophospholipid contained in oxidized low-density lipoprotein (ox-LDL), induces endothelial dysfunction. Recent studies showed that natriuretic peptides (NPs) have antiatherogenic properties by inhibiting vascular smooth-muscle cell proliferation, but their effects on endothelial cells are little known. We examined whether atrial and brain NPs (ANP and BNP) have a protecting action against LPC-induced endothelial dysfunction. LPC (10 microM) significantly inhibited thrombin (0.001-1 U/ml)-induced endothelium-dependent relaxation without affecting endothelium-independent relaxation to sodium nitroprusside in isolated porcine coronary arteries. The impaired endothelium-dependent relaxation induced by LPC was prevented by treatment with ANP or BNP (i microM). In cultured bovine aortic endothelial cells (BAECs), LPC (10 microM) significantly attenuated bradykinin (1 microM)-stimulated nitric oxide (NO) release; however, this was prevented by ANP and BNP. Because LPC-induced endothelial dysfunction has been shown to be mediated at least in part by activation of the protein kinase C (PKC)-dependent signaling pathway, we also examined the effects of ANP and BNP on LPC-induced modulation of PKC activities in BAECs. LPC (10 microM) significantly stimulated PKC activity in BAECs. However, ANP or BNP significantly inhibited LPC (10 microM)-induced PKC activation. In conclusion, ANP and BNP protected endothelial cells from LPC-induced dysfunction in both isolated coronary arteries and cultured ECs. The mechanism appears to be at least in part related to the inhibition of LPC-induced PKC activation by NPs. These new actions of ANP and BNP against lysolipid-induced endothelial cytotoxicity may partly account for antiatherogenic properties of NPs.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Atrial Natriuretic Factor; Cattle; Coronary Vessels; Dinoprost; Endothelium, Vascular; Enzyme Activation; In Vitro Techniques; Lysophosphatidylcholines; Muscle Relaxation; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Nitrates; Nitric Oxide; Nitrites; Protein Kinase C; Signal Transduction; Swine; Vascular Diseases