Ilaria Quatrini

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.

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.

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.

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.

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.

Plasma brain natriuretic peptide levels in coronary heart disease with preserved systolic function

Abstract.We evaluated the circulating levels of brain natriuretic peptide (BNP) in stable angina, unstable angina, and myocardial infarction relating hormone levels to extension of coronary disease and number of vessels involved after angiographic examination. We studied 86 patients consecutively undergoing angiographic coronary examination and echocardiographic evaluation for coronary heart disease. These included 15 control subjects (group 0), 21 with stable angina (group I), 26 with unstable angina (group II), and 24 with non-Q myocardial infarction (group III). Patients with heart failure, a history of myocardial infarction, or recent myocardial damage with electrocardiographic S-T elevation were excluded. BNP levels in patients with unstable angina and myocardial infarction were significantly increased with respect to the group with stable angina (P<0.01). There were no differences between the groups with unstable angina and myocardial infarction. Analysis of peptide levels in relation to the number of involved vessels demonstrated a significant increase in patients with three-vessel disease compared with subjects with one or two vessels involved (P<0.03); among subjects with mono-vessel disease, patients with left descendent anterior stenosis had a moremarked BNP elevation than subjects with stenosis in other regions (P<0.01). Hence, BNP levels appear to be elevated in coronary disease, especially in acute coronary syndromes, even in the absence of systolic dysfunction. BNP levels also seem to be related to the severity of coronary atherosclerosis and number of vessels involved. BNP could prove a novel marker for risk stratification, not only in heart failure but also in coronary heart disease.

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.

Coronary artery-pulmonary artery fistula: case report

BackgroundCoronary 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 presentationAn 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.ConclusionA 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%.

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.