Hypertension, left ventricular hypertrophy and chronic kidney disease.

Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease. LVH in CKD patients has generally a negative prognostic value, because it represents an independent risk factor for the development of arrhythmias, sudden death, heart failure and ischemic heart disease. LVH in CKD patients is secondary to both pressure and volume overload. Pressure overload is secondary to preexisting hypertension, but also to a loss of elasticity of the vessels and to vascular calcifications, leading to augmented pulse pressure. Anemia and the retention of sodium and water secondary to decreased renal function are responsible for volume overload, determining a hyperdynamic state. In particular, the correction of anemia with erythropoietin in CKD patients is advantageous, since it determines LVH reduction. Other risk factors for LVH in CKD patients are documented: some are specific to CKD, as mineral metabolism disorders (hypocalcemia, hyperphosphatemia, low serum vitamin D levels and secondary hyperparathyroidism), others are non-traditional, such as increased asymmetric dimethylarginine, oxidative stress, hyperhomocysteinemia and endothelial dysfunction that, in turn, accelerates the process of atherogenesis, triggers the inflammation and pro-thrombotic state of the glomerular and the vascular endothelium and aggravates the process of both CKD and LVH.

Beta-erythropoietin effects on ventricular remodeling, left and right systolic function, pulmonary pressure, and hospitalizations in patients affected with heart failure and anemia.

Anemia in heart failure is related to advanced New York Heart Association classes, severe systolic dysfunction, and reduced exercise tolerance. Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its' correction with erythropoietin (EPO) on cardiac structure and function. The present study examines, in patients with advanced CHF and anemia, the effects of beta-EPO on left ventricular volumes, left ventricular ejection fraction (LVEF), left and right longitudinal function mitral anular plane systolic excursion (MAPSE), tricuspid anular plane excursion (TAPSE), and pulmonary artery pressures in 58 patients during 1-year follow-up in a double-blind controlled study of correction of anemia with subcutaneous beta-EPO. Echocardiographic evaluation, B-Type natriuretic peptide (BNP) levels, and hematological parameters are reported at 4 and 12 months. The patients in group A after 4 months of follow-up period demonstrated an increase in LVEF and MAPSE (P < 0.05 and P < 0.01, respectively) with left ventricular systolic volume reduction (P < 0.02) with respect to baseline and controls. After 12 months, results regarding left ventricular systolic volume LVEF and MAPSE persisted (P < 0.001). In addition, TAPSE increased and pulmonary artery pressures fell significantly in group A (P < 0.01). All these changes occurred together with a significant BNP reduction and significant hemoglobin increase in the treated group. Therefore, we revealed a reduced hospitalization rate in treated patients with respect to the controls (25% in treated vs. 54% in controls). In patients with anemia and CHF, correction of anemia with beta-EPO and oral iron over 1 year leads to an improvement in left and right ventricular systolic function by reducing cardiac remodeling, BNP levels, and hospitalization rate.

Osteoprotegerin and B-type natriuretic peptide in non-ST elevation acute coronary syndromes: relation to coronary artery narrowing and plaques number.

BACKGROUND: To analyse osteoprotegerin (OPG), and B-type natriuretic peptide (BNP) levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. OPG has been found in several tissues, including the cardiovascular system, BNP is selectively produced by myocardial cells. METHODS: 178 consecutive patients were classified in three groups: stable angina (SA), unstable angina/non-ST elevation myocardial infarction (NSTE-ACS) and control group, measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-, 2- , 3- or 4- vessels disease), and to the stenoses degree by Duke Jeopardy score. RESULTS: OPG levels were higher in patients respect to controls (p<0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients with NSTE-ACS had higher OPG level with respect to SA patients (11.8+/-7.1 pmol/l p<0.001). A positive relation was found between OPG levels and number of coronary plaques by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with NSTE-ACS respect to controls and SA patients (p<0.001). Besides, BNP was significantly higher in multivessels vs 1-vessel disease (p<0.001). CONCLUSIONS: Patients with NSTE-ACS show high OPG levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the coronary disease progression. BNP is also increased during NSTE-ACS and more associated to coronary narrowing.

Prevalence of risk factors, coronary and systemic atherosclerosis in abdominal aortic aneurysm: comparison with high cardiovascular risk population.

BACKGROUND: Abdominal aortic aneurysm (AAA) is considered a manifestation of atherosclerosis, however there are epidemiologic, biochemical, and structural differences between occlusive atherosclerosis and AAA. The pathogenesis of AAA involves several factors, first of all destruction of collagen and elastin in the aortic wall. Classical risk factors may influence the evolution and development of AAA, though no consistent association has been found. Aims of the study were to evaluate associations between risk factors and to establish the prevalence of carotid, peripheral vascular and coronary atherosclerosis in patients with AAA. METHODS: We studied 98 patients with AAA (Group 1) awaiting surgery compared with high cardiovascular risk population having two or more risk factors (n=82 Group 2). We evaluated traditional risk factors and we studied by eco-doppler and echocardiography the presence of carotid peripheral and coronaric atherosclerosis in two groups. RESULTS: We found a higher incidence of AAA in males (p < 0.01). The prevalence of infrarenal AAA was significantly higher than suprarenal AAA (81 vs. 17 p < 0.001). No differences in total cholesterol (199 +/- 20 vs. 197 +/- 25 mg/dl), low-density lipoprotein (142 +/- 16 vs. 140 +/- 18 mg/dl), triglycerides (138 +/- 45 vs. 144 +/- 56 mg/dl), glycemia (119 +/- 15 vs. 122 +/- 20 mg/dl), and fibrinogen (388 +/- 154 vs. 362 +/- 92 mg/dl) were found between groups. We demonstrated significant differences for cigarette smoking (p < 0.002), systolic and diastolic blood pressure (150 +/- 15 vs. 143 +/- 14 mmHg and 88 +/- 6 vs. 85 +/- 7 mmHg, p < 0.0001 and p < 0.05, respectively) and high sensititivity C reactive protein (2.8 +/- 1.3 vs. 1.3 +/- 0.7 mg/dl, p < 0.001). High-density lipoprotein (HDL) cholesterol levels were significant greater in Group 1 than Group 2 (p < 0.003). Subgroups of patients with AAA and luminal thrombus showed higher fibrinogen levels (564 +/- 235 vs. 341 +/- 83 mg/dl, p < 0.001) and lower HDL than in controls (46.6 +/- 6.5 vs. 52.1 +/- 7.8 mg/dl, p < 0.01). We did not find any difference in body mass index, or prevalence of coronary and peripheral atherosclerosis between groups. Conversely, we found higher prevalence of carotid atherosclerosis in Group 2 (9% vs. 25%, p < 0.004). CONCLUSION: Our AAA patients had fewer and different risk factors respect to patients with atherosclerosis. Only elevated blood pressure, C reactive protein, and smoking showed a significant association with AAA. Atherosclerosis in other arterial districts did not differ respect to subjects with high cardiovascular risk. Our results confirm the hypothesis that AAA and atherosclerosis are two different pathological entities with different risk profiles.

Coronary artery-pulmonary artery fistula: case report.

BACKGROUND: Coronary artery fistulas are rare congenital or acquired coronary artery anomalies that can originate from any of the three major coronary arteries and drain in all the cardiac chambers and great vessels. CASE PRESENTATION: An 11-year-old boy was referred for evaluation of an exertional dyspnoea. He reported recent history of few episodes of shortness of breath associated with moderate entity physical activity. At physical examination a mild continuous murmur could be heard mainly at the level of the second intercostal space of the left parasternal area. A transthoracic echocardiogram showed a continuous flow at color Doppler analysis in the high parasternal short axis view, originating from a small entry site on the wall of the main pulmonary artery. A selective left coronary angiography revealed a fistula connecting the proximal portion of the left anterior descending coronary artery with the main pulmonary artery. CONCLUSION: A combination like the one described in the present case is unusual since fistulas originate from the left coronary artery in about 35% of cases and drainage into the pulmonary artery occurs in only 17%.

Relation of plasma brain natriuretic peptide levels in non-ST-elevation coronary disease and preserved systolic function to number of narrowed coronary arteries.

Elevated plasma brain natriuretic peptide (BNP) levels have been described in patients with acute myocardial infarction and left ventricular dysfunction. The aim of the present study was to evaluate circulating BNP levels in patients with coronary artery disease without ST-segment elevation acute myocardial infarction and preserved systolic function and to evaluate the BNP levels in relation to the number of involved coronary vessels. We studied 88 patients with coronary artery disease: group 1 had stable angina, group 2 had unstable angina (UA), group 3 had non-Q-wave myocardial infarction (NSTEMI), and group 0 consisted of 15 healthy subjects. All recruited subjects underwent angiographic examination and echocardiographic evaluation. No patients had heart failure, previous myocardial infarction, or electrocardiographic ST elevation. A significant increase in BNP levels was observed in the UA and NSTEMI groups compared with the stable angina group (stable angina 31.3 pg/ml, UA 147.3 pg/ml, NSTEMI, 165.8 pg/ml, p <0.01), and no differences were found between the UA and NSTEMI groups. Analysis of BNP in relation to the number of involved vessels showed significantly higher BNP levels in patients with 3- than in those with 1- or 2-vessel disease (1 to 45.2, 2 to 127.3, and 3 to 220.8 pg/ml, respectively, p <0.05 and p <0.0001, 3 vs 1- and 2-vessel disease, p = 0.01, respectively). Patients with left anterior descending stenosis had higher BNP levels than those with stenosis in other areas (150.8 vs 52.2 pg/ml, p <0.01). In conclusion, circulating BNP levels appeared elevated in patients with acute coronary syndromes with diffuse coronary involvement, even in the absence of systolic dysfunction or heart failure. BNP was also associated with multivessel disease and left anterior descending involvement.

Brain natriuretic peptide levels during cardiac reperfusion: comparison between percutaneous coronary angioplasty and aorto-coronaric bypass.

BACKGROUND: Several studies have documented brain natriuretic peptide (BNP) behavior during cardiac ischemia and after myocardial necrosis. Peptide levels have been shown to be increased during acute phase of cardiac ischemia and during late ventricular remodelling; however, there are fewer data about hormone levels during percutaneous transluminal coronary angioplasty (PTCA) and aorto-coronaric by pass (CABG). METHODS: Aim of this study was to investigate plasma BNP during acute or sub-acute myocardial ischemia in patients undergoing to PTCA or CABG, taking blood samples before and after both procedures. We studied 59 consecutive subjects, 25 submitted to coronary by-pass and 34 submitted to coronary angioplasty. Blood BNP levels were measured the day before intervention and after 3, 7 and 90 days from the procedures. RESULTS: Peptide levels were significantly different just before intervention (GABG group 118.7+/-81 pg/ml vs. PTCA group 34.8+/-15 pg/ml, p<0.01). This difference was increased after 3 days (CABG group 403.2+/-185 pg/ml vs. PTCA group 105.3+/-56 pg/ml, p<0.0001) and after 7 days (CABG group 252.2+/-93 pg/ml vs. PTCA group 69.8+/-36 pg/ml, p<0.00001). These results trend to converge after 90 days (CABG group +/-93 pg/ml vs. PTCA group +/-36 pg/ml, p<0.05). CONCLUSIONS: Plasma BNP shows a different behavior during and after different myocardial reperfusion procedures. PTCA causes only mild and temporary elevation of peptide levels, otherwise CABG demonstrates a more enhancing of BNP release not only in early phase but also after one week; increased levels tend to return towards the reference range after few weeks from cardiac surgery.

Natriuretic peptides in heart failure: where we are, where we are going.

Tremendous advances have been made in understanding the pathophysiology and treatment of congestive heart failure (CHF). However, diagnosis still remains difficult, even with a comprehensive physical examination. Symptoms such as dyspnea are non-specific and poorly sensitive indicators for early CHF that can be largely undetected. The discovery of natriuretic peptides (BNP) as diagnostic biomarkers has been one of the most critical advances for heart failure diagnosis. Therefore, both B-type and N-terminal pro-B-type have potential role in the diagnosis of heart failure, as well as in prognostic risk assessment. A single determination of BNP at any time during the progression of chronic HF provides a clinically useful tool for risk stratification. The hypothesis that repeated measurements might carry prognostic information beyond a single measure was confirmed in different settings. One of the main interests is given to the values of repeated determinations for monitoring progression of disease, and for the evaluation of the clinical effects of medical therapy. Nevertheless, despite thousands of papers describing their potential utility, current guidelines have not endorsed the highest level of recommendation for their use, in part, because the application in clinical practice is often limited for the absence of well codified cut off. Recently, European guidelines emphasized the role of natriuretic peptides as potential laboratory markers. In the near future, algorithm building will take into consideration clinical and echocardiographic parameters as well as NP measurements, and this may lead to a correct diagnosis and identification of patients at high risk. The purpose of this review is to discuss the clinical approaches and future applications of natriuretic peptides in heart failure and coronary disease.

Anemia correction by erythropoietin reduces BNP levels, hospitalization rate, and NYHA class in patients with cardio-renal anemia syndrome.

Little is known about the effect of anemia correction with erythropoietin (EPO) on B-type natriuretic peptide (BNP) levels, NYHA class, and hospitalization rate. The aim of the study was to investigate, in patients with cardio-renal anemia syndrome, the effects of EPO on hemochrome and renal function parameters and BNP levels. We also analyzed the effect of EPO therapy on hospitalization rate and NYHA class after 12 months in comparison with a population undergoing to standard therapy. We performed a randomized double-blind controlled study of correction of the anemia with subcutaneous α (group A n = 13) or ß (group B n = 14) EPO for 12 months in addition to standard therapy with oral iron in 27 subjects. Control group (n = 25 patients) received only oral iron. Significant increase in hemoglobin (Hb), hematocrit (Hct), and red blood cells (RBC) were revealed in EPO groups at 12 months; Hb, group A 12.3 ± 0.6; group B 11.7 ± 0.8; control group 10.6 ± 0.5 g/dl P < 0.0001; Hct group A 34.2 ± 2.3, group B 34 ± 2, control group 32.3 ± 1.8% P < 0.01; RBC, group A 3.9 ± 0.2, group B 3.8 ± 0.2, control group 3.3 ± 0.2, (P < 0.0001). Plasma BNP levels in EPO groups were significantly reduced after 12 months (group A: 335 ± 138 vs. group B: 449 ± 274 pg/ml control group 582 ± 209 pg/ml (P < 0.01). After 12 months of treatment, hospitalization rate and NYHA class were reduced in EPO groups with respect to control group (P < 0.05). Finally, an inverse correlation was observed between BNP and Hb levels in EPO Groups (r = -0.70 P < 0.001). EPO treatment reduces BNP levels and hospitalization rate in patients with cardio-renal anemia syndrome. The correction of anemia by EPO treatment appears able to improve clinical outcome in this subset of patients with heart failure.

B-type natriuretic peptide levels predict extent and severity of coronary disease in non-ST elevation coronary syndromes and normal left ventricular systolic function.

BACKGROUND: B-type natriuretic peptide (BNP) has been used recently as a biological marker in patients with coronary artery disease (CAD) with ST-elevation, as well as without ST-elevation. BNP is able to predict systolic dysfunction, adding new prognostic information to existing traditional markers. However is not known if there is a relation between the quantity of BNP levels and the severity of coronary artery disease. METHODS: This study compared B-type natriuretic peptide (BNP) levels in patients with stable angina (SA) and acute coronary syndromes (ACS) without ST-elevation in relation to angiographic lesions using TIMI and Gensini Scores. We studied 282 patients with CAD without ST elevation and preserved systolic function. BNP samples were measured in all recruited patients within 24 hours of hospitalization. RESULTS: BNP values were progressively increased in relation to the severity of diagnosis: SA (52.6±49.4 pg/mL ) UA (243.3±212 pg/mL) NSTE-ACS (421.7±334 pg/mL) (p<0.0001 and p<0.007 respectively). No statistically significant difference was observed between patients with SA and controls (21.2±6.8 pg/mL). The analysis of BNP levels in relation to the number of involved vessels demonstrated significantly increased levels in patients with multivessel disease compared to patients with 1 or 2 vessel disease (1-86.2±46.3 pg/mL; 2-127±297 pg/mL; 3-295±318 pg/mL; 4-297±347 pg/mL p<0.001 and p<0.003). Evaluation of BNP using Gensini Score showed a strong relation between BNP and coronary disease extension (r=0.38 p<0.0001).This trend was maintained in all CAD groups (SA=r 0.54; UA r=0.36 NSTE-ACS r=0.28). CONCLUSIONS: Circulating BNP levels appear elevated in ACS with diffuse coronary involvement, even in the absence of systolic dysfunction. BNP is also associated with multi-vessel disease and the extension of coronary disease.

Osteoprotegerin and B-type natriuretic peptide in acute coronary syndromes with preserved systolic function: relation to coronary artery disease extension.

OBJECTIVES: To analyze Osteoprotegerin (OPG), and BNP plasma levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. METHODS: 155 CAD patients were classified in four groups: stable angina (SA n=42), unstable angina (UA n=35) non-ST elevation myocardial infarction (NSTEMI n=45) and control group (n=33), measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-,2-,3 or more vessels disease), and to the stenoses degree by Duke Jeopardy score. RESULTS: OPG levels were higher in patients with CAD respect to controls (p<0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients with UA and NSTEMI had higher OPG level with respect to SA patients (12.2+/-7.8 and 11.6+/-6.1 respectively pmol/l p<0.001). A positive relation was found between OPG levels and coronary plaques extension by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with UA/NSTEMI respect to controls and SA patients (p<0.001). Besides, BNP was significantly higher in patients with multi-vessels vs 1-vessel disease (p<0.001). CONCLUSIONS: Patients with UA and NSTEMI show high OPG and BNP levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the CAD progression.

Circumferential versus longitudinal systolic function in patients with hypertension: a nonlinear relation.

BACKGROUND: Depressed circumferential midwall performance and impaired left ventricular (LV) longitudinal function are both early markers of LV systolic dysfunction in patients with hypertension. The relation between midwall and longitudinal indices in these patients has never been analyzed. METHODS: In 126 patients with hypertension, midwall fractional shortening (mFS), stress-corrected mFS, M-mode left atrioventricular plane displacement, and tissue Doppler-derived peak mitral annular systolic velocity were determined. RESULTS: Regression analysis showed that the relations of midwall indices to atrioventricular plane displacement and mitral annular systolic velocity were all nonlinear. Reductions in atrioventricular plane displacement or mitral annular systolic velocity within their higher ranges corresponded to relatively smaller decreases in mFS and stress-corrected mFS. Relative wall thickness was the strongest determinant of the relative efficiency of circumferential and longitudinal LV contraction. CONCLUSION: The relation between circumferential midwall and longitudinal function in patients with hypertension is nonlinear and dependent on LV geometry. In these patients, systolic impairment occurs earlier in longitudinal than circumferential performance.

Left ventricular diastolic function improvement by carvedilol therapy in advanced heart failure.

Carvedilol treatment in chronic heart failure (CHF) patients has been demonstrated to reduce mortality by improving cardiac systolic function and reducing left ventricular adverse remodeling. However, the effects of the drug on left ventricular (LV) filling are less studied. In this study we evaluated early and long-term diastolic cardiac modifications by an echo-Doppler method during carvedilol therapy in patients with advanced CHF and pseudonormal or restrictive filling pattern. We studied 58 patients with severe but stable CHF (39 in class NYHA III and 19 in IV) having systolic and diastolic dysfunction caused by idiopathic or ischemic cardiomyopathy. Thirty-two patients were randomized to receive previous treatment plus carvedilol (group 1) and 26 continued standard therapy (group 2). In all subjects we evaluated LV volumes, LV mass, LV ejection fraction (EF), and the following transmitral filling parameters: early wave (E), atrial wave (A), E/A ratio, deceleration time (DT), and isovolumetric releasing time (IVRT). After 4 months of therapy, the carvedilol group showed a significant increase of A wave (P < 0.001), DT (P < 0.0001), IVRT (P < 0.0001), and a significant reduction of E/A ratio (P < 0.0005) with respect to group 2. Further improvement was observed at 12 months (A P < 0.0005; DT P < 0.00002; IVRT P < 0.000004; E/A P < 0.0008), although an E wave reduction was observed in group 1 with respect to controls (P < 0.001). Moreover, after 1 year of follow-up a reduction of systolic volume (P < 0.001) and pulmonary pressure (P < 0.0001) and consequent increase of EF (P < 0.001) was observed in the carvedilol group. Carvedilol treatment improved diastolic function in CHF with severe diastolic and systolic impairment at early time, converting a restrictive or pseudonormal filling pattern into an altered pattern. These changes remained significant after 1 year of therapy together with improvement in systolic function.