Biomarkers and echocardiographic predictors of myocardial dysfunction in patients with hypertension.

The study aimed to identify early echocardiographic and circulating biomarkers of heart failure (HF) in hypertensive patients with normal resting echocardiography. Echocardiography at rest and during exercise, and selected biomarkers were assessed in control group, dyspnea group, and HF group. On exercise dyspnea patients had lower early diastolic (E') and systolic (S') mitral annular velocity (12.8 ± 1.0 vs 14.9 ± 3.0 cm/sec and 9.3 ± 2.0 vs 10.9 ± 2.0 cm/sec, respectively), and higher E/E' ratio compared to control group (6.7 ± 1.0 vs 5.9 ± 1.0) (p < 0.05 for all comparisons). The level of N-terminal propeptide of procollagen type III (PIIINP) was significantly higher in dyspnea group than in controls (p = 0.01). Control and dyspnea patients had lower levels of cardiotrophin-1, cystatin C, syndecan-4, and N terminal-probrain natriuretic peptide than HF patients (all p ≤ 0.01). In multivariate analysis PIIINP (unadjusted odds ratio [OR] = 8.2, 95% confidence interval [Cl] 1.7-40.6; p = 0.001; adjusted OR = 8.7; 95%CI: 1.5-48.3; p = 0.001) and E/E' ratio on exercise (unadjusted OR = 1.8, 95%CI: 0.8-4.0; p = 0.033; adjusted OR = 2.0; 95%CI: 0.8-4.8; p = 0.012) were the only factors significantly associated with the presence of dyspnea. PIIINP is the first early biomarker for the HF development in patients with HA and normal resting echocardiography. Exertional echocardiography may indicate patients with incipient HF with preserved ejection fraction.

Heart function disturbances in chronic kidney disease - echocardiographic indices.

INTRODUCTION: In chronic kidney disease (CKD) patients left ventricular (LV) diastolic dysfunction occurs frequently and is associated with heart failure (HF) and higher mortality. Left ventricular systolic dysfunction is associated with coronary artery disease (CAD) and is a major determinant of prognosis. The aim of this study was to assess indices of LV diastolic dysfunction in CKD patients. MATERIAL AND METHODS: Study included 118 CKD patients. All patients underwent transthoracic echocardiography. Diastolic function based on E and A, E/A ratio and pulmonary vein flow velocities as well as EF%, deceleration time, RA, LA volume were assessed. In dialysis patients examination was carried out before and after dialysis. RESULTS: In CKD patients the stage of renal failure was associated with the significant increase in LV mass (268.0 ±47.6 CKD I/II vs. 432.7 ±122.4 CKD V/dialysis, p < 0.0001), systolic LV (37.3 ±4.5 vs. 51.2 ±8.9, p < 0.0001) and diastolic LV (CKD I-II 44.7 ±4.1 vs. CKD III 48.5 ±6.7 vs. CKD IV 47.1 ±5.6; p = 0.004) dimensions and in the size of the LA (40.4 ±2.0 vs. 41.9 ±2.7 vs. 42.3 ±3.2 vs. 44.8 ±3.1; p < 0.0001). The increase the E/E' ratio between groups of patients (6.7 ±1.5 vs. 8.9 ±2.4 vs. 11.5 ±4.0 vs. 13.5 ±5.0; p < 0.0001) was seen in this study. The reduction in deceleration time (247.2 ±34.5 in CKD I/II vs. 197.4 ±61.0 in CKD IV, p = 0.0005) along with the decrease in estimated glomerular filtration rate was also observed in this study. CONCLUSIONS: Early identification of factors involved is necessary to prevent this devastating process. Many indexes of contractility are used and each of them has imperfections. It seems that TVI, E, E/A and E/E' are good instruments for the early detection of left ventricular hypertrophy and diastolic dysfunction.

The risk of atherosclerosis in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is becoming a serious health problem; the number of people with impaired renal function is rapidly rising, especially in industrialized countries. A major complication of CKD is cardiovascular disease. Accelerated atherosclerosis has been observed in early stages of renal dysfunction. The purpose of this study was to examine the relationship between the degree of renal insufficiency and both the prevalence and intensity of coronary artery disease (assessed on the basis of number of vessels with stenosis). METHODS: 446 individuals with both serum creatinine >120 µmol/l (men) or >96 µmol/l (women) and acute coronary syndrome were included in the study. All patients included in this analysis underwent urgent coronarography. Data concerning glomerular filtration rate (GFR), number of vessels with stenosis, hypertension, lipid disorders, creatinine concentration, C-reactive protein, glucose and lipid profile were analyzed. RESULTS: This study confirmed that moderate to severe renal impairment is associated with accelerated atherosclerosis. Moreover, patients with GFR values below 60 ml/min/1.73 m(2) are predisposed to accelerated, multivessel cardiovascular disease. CONCLUSIONS: GFR seems to be an independent risk factor for multivessel cardiovascular disease. Due to the fact that patients with renal dysfunction are at high risk of cardiovascular events, they should obtain optimal treatment resulting not only in kidney protection but also in the elimination of cardiovascular risk factors.

Statin therapy and new-onset diabetes: molecular mechanisms and clinical relevance.

Despite positive effects on the plasma lipid profile and vascular events, statin use is associated with various side effects. Among these, statins might cause a disruption of a number of regulatory pathways including insulin signaling. This may affect insulin sensitivity, pancreatic beta-cell function and adipokine secretion. The statin-associated risk of new-onset diabetes (NOD) appears to be a dose-dependent class effect. It still remains unclear whether statin treatment is associated with increased risk of NOD in the general population or if there are groups of individuals at particular risk. However, according to the available data it seems that cardiovascular (CV) benefits in high-risk individuals strongly favor statin therapy since it outweighs other risks. Whether statins should be used for primary prevention among patients with a relatively low baseline CV risk is still questionable, however the results of primary prevention trials have shown reductions in mortality in this population. Thus, there is a need for randomized, placebo-controlled statin studies with carefully selected groups of patients and NOD as a key end point in order to resolve queries concerning this issue.

Metabolic syndrome and renal disease.

The metabolic syndrome (MetS) is a cluster of risk factors including insulin resistance, dyslipidemia and hypertension which are also relevant for the development of chronic kidney disease (CKD). It has proven difficult to elucidate whether the renal dysfunction in MetS is due to the MetS itself or the individual risk factors. For example, obesity - which is also part of the MetS - may enhance the risk of renal dysfunction development probably through mechanisms associated with renal hyperfiltration, hyperperfusion and focal glomerulosclerosis. Insulin resistance also promotes kidney disease by worsening renal hemodynamics. In patients with MetS, tubular atrophy, interstitial fibrosis, and arteriolar sclerosis indicating the presence of vascular damage, have also been described. As yet, there has been little evidence that preventing or treating symptoms of the MetS protects patients from renal impairment.

Acute coronary syndromes in patients with chronic kidney disease.

Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality. The available data suggest that efforts to reduce mortality in the CKD population should be focused on treatment and prevention of, among others, coronary artery disease and congestive heart failure. Accelerated atherosclerosis present in CKD patients also leads to a decline in renal function. Definite data concerning the treatment of heart failure in CKD patients are lacking, because patients with significant renal impairment have mostly been excluded from randomized studies. Nevertheless, it seems that CKD patients should receive similar cardiovascular treatment to that used in patients with normal kidney function, but the doses of drugs ought to be titrated to achieve an optimal effect while avoiding adverse events. Several studies have also shown that despite the high risk, in patients with acute coronary syndrome (ACS), revascularization procedures in patients with CKD appear to be advantageous in the long run and are therefore justified. However, large clinical trials are needed to confirm the benefits and to identify possible disadvantages associated with various methods of treatment.

Treatment of non-ST-elevation myocardial infarction and ST-elevation myocardial infarction in patients with chronic kidney disease.

Renal dysfunction is frequent in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Chronic kidney disease (CKD) is associated with very poor prognosis and is an independent predictor of early and late mortality and major bleeding in patients with NSTE-ACS. Patients with NSTE-ACS and CKD are still rarely treated according to guidelines. Medical registers reveal that patients with CKD are usually treated with too high doses of antithrombotics, especially anticoagulants and inhibitors of platelet glycoprotein (GP) IIb/IIIa receptors, and therefore they are more prone to bleeding. Drugs which are excreted mainly or exclusively by the kidney should be administered in a reduced dose or discontinued in patients with CKD. These drugs include enoxaparin, fondaparinux, bivalirudin, and small molecule inhibitors of GP IIb/IIIa inhibitors. In long-term treatment of patients after myocardial infarction, anti-platelet therapy, lipid-lowering therapy and ß-blockers are used. Chronic kidney disease patients before qualification for coronary interventions should be carefully selected in order to avoid their use in the group of patients who could not benefit from such procedures. This paper presents schemes of non-ST and ST-segment elevation myocardial infarction treatment in CKD patients in accordance with the current recommendations of the European Society of Cardiology (ESC).

Prevention of sudden cardiac death in patients with chronic kidney disease.

Cardiovascular deaths account for about 40% of all deaths of patients with chronic kidney disease (CKD), particularly those on dialysis, while sudden cardiac death (SCD) might be responsible for as many as 60% of SCD in patients undergoing dialysis. Studies have demonstrated a number of factors occurring in hemodialysis (HD) that could lead to cardiac arrhythmias. Patients with CKD undergoing HD are at high risk of ventricular arrhythmia and SCD since changes associated with renal failure and hemodialysis-related disorders overlap. Antiarrhythmic therapy is much more difficult in patients with CKD, but the general principles are similar to those in patients with normal renal function - at first, the cause of arrhythmias should be found and eliminated. Also the choice of therapy is narrowed due to the altered pharmacokinetics of many drugs resulting from renal failure, neurotoxicity of certain drugs and their complex interactions. Cardiac pacing in elderly patients is a common method of treatment. Assessment of patients' prognosis is important when deciding whether to implant complex devices. There are reports concerning greater risk of surgical complications, which depends also on the extent of the surgical site. The decision concerning implantation of a pacing system in patients with CKD should be made on the basis of individual assessment of the patient.

An update on biomarkers of heart failure in hypertensive patients.

Biomarkers should have high sensitivity, specificity, reproducibility, be cost-effective, and provide incremental predictive or diagnostic utility over standard risk factors or tests. Despite numerous studies investigating biomarkers in heart failure (HF), there are only a few that predict HF in hypertensive patients. This article summarizes data from numerous studies concerning possible biomarkers of HF in hypertensive patients such as: serum uric acid (SUA), interleukins, monocyte chemoattractant protein one (MCP-1), cardiotrophin-1 (CT-1), carboxy-terminal propeptide of procollagen type I (PICP), type I collagen telopeptide (CITP) and N-terminal propeptide of type III procollagen (PIIINP), metalloproteinases (MMPs), B-type natriuretic peptide (BNP) and its derivatives, glycoprotein CA125 and cystatin C. Early detection of patients of increased risk of hypertensive heart disease may result in early implementation of effective preventive strategies. Therefore, there is need to identify newer biomarkers, if they can improve risk prediction, identifying patients, in which earlier or more aggressive intervention will improve clinical outcomes.

Statins in patients with chronic kidney disease: why, who and when?

IMPORTANCE OF THE FIELD: Patients with end-stage renal disease are at high risk of developing cardiovascular disease, which is characterized by early onset and rapid progression of atherosclerosis. Some analyses of large clinical trials have revealed that statins might reduce all-cause mortality and cardiovascular (CV) events in patients with chronic kidney disease (CKD). Preliminary studies have also suggested that they can reduce contrast-induced nephropathy (CIN) and the rate of loss of kidney function. However, the results concerning the efficacy and safety of statin therapy in patients with CKD, especially in those on renal replacement therapy, are still controversial. AREAS COVERED IN THIS REVIEW: This review contains data on the atherosclerotic risk in patients with CKD; the role of statins in the reduction of CV risk in patients with CKD; the role of CIN; the effects of statins on retarding the progression of CKD; and the efficacy of statin therapy in CKD, dialysis and renal-transplant patients. We searched using the electronic databases [MEDLINE (1966 - June 2010), EMBASE and SCOPUS (1965 - June 2010), DARE (1966 - June 2010)]. Additionally, abstracts from national and international cardiovascular meetings were studied. Where necessary, the relevant authors of these studies were contacted to obtain further data. The main data search terms were: 'statin/statins', 'dialysis', 'dyslipidemia', 'hemodialysis', 'kidney disease', 'microalbuminuria', 'clinical trials', and 'renal impairment'. WHAT THE READER WILL GAIN: Readers will be acquainted with results of clinical trials, including the most recent ones (e.g., PLANETE I and II), and will be able to draw their own conclusions concerning the use of statins in CKD patients on the basis of the results of the studies presented and to compare them with the authors' suggestions presented in this review. TAKE HOME MESSAGE: Although the results of trials are conflicting, it is suggested that the benefits of statin use outweigh the drawbacks in patients with early-stage CKD, when the benefits can be effectively predicted. However, available large randomized clinical trials suggest a lack of efficacy in patients on renal replacement therapy.

The role of polyphenols in cardiovascular disease.

Epidemiological studies suggest that diets rich in polyphenols may be associated with reduced incidence of cardiovascular disorders (mainly coronary heart disease and myocardial infarction). However, the mechanisms explaining this correlation have not been fully elucidated. Current evidence suggests that polyphenols, acting at the molecular level, improve endothelial function and inhibit platelet aggregation. In view of their antithrombotic, anti-inflammatory, and anti-aggregative properties, these compounds may play a roles in the prevention and treatment of cardiovascular disease.

The role of Toll-like receptors in renal diseases.

Toll-like receptors (TLRs) have a key role in innate immunity. These receptors recognize both pathogen-associated molecular patterns and molecules that are released from damaged tissue. TLRs mediate signal transduction pathways through the activation of transcription factors that regulate the expression of proinflammatory cytokines and chemokines and are required for the development of adaptive immune responses. TLRs might have an important role in the pathogenesis of renal diseases: their exaggerated activation is associated with ischemic kidney damage, acute kidney injury, end-stage renal failure, acute tubulointerstitial nephritis, acute renal transplant rejection and delayed allograft function. As the results of previous studies concerning the role of TLRs in renal diseases are conflicting, further work is needed to determine the exact role of these receptors and to evaluate strategies to prevent TLR-mediated local inflammation. This Review discusses the evidence supporting a role for TLRs in contrasting bacterial infections and in causing or aggravating renal conditions when TLR activation leads to a harmful inflammatory response.

The role of polymorphisms within paraoxonases (192 Gln/Arg in PON1 and 311Ser/Cys in PON2) in the modulation of cardiovascular risk: a pilot study.

Paraoxonases (PONs) may exert anti-atherogenic action by reducing lipid peroxidation. We evaluated the influence of 2 polymorphisms within PON1 (192 Gln/ Arg) and PON2 (311 Ser/Cys) genes in 407 young Poles: 273 patients who experienced a first myocardial infarction (MI) under the age of 45 (study group) and 134 healthy volunteers (control group) with a HEART Score < or =2 (low risk). Paraoxonase 1 polymorphism 192Gln/Arg influenced the risk of premature MI (P = .0054). A positive family history of coronary artery disease (CAD) was associated with the 192Arg allele (P = .0107). The association between PON1 genotype (192 Gln/Arg) and low-density lipoprotein cholesterol (LDL-C) (P = .036) levels was also observed. However, we did not find any relationship between polymorphism 311Ser/Cys and CAD risk (P = .418). PON1 polymorphism 192Gln/Arg influenced the risk of premature MI. The association between PON1 genotype (192 Gln/Arg) and serum LDL-C levels may be explained by PON participation in reverse cholesterol transport.

Genetic determinants of cardiovascular disease: the renin-angiotensin-aldosterone system, paraoxonases, endothelin-1, nitric oxide synthase and adrenergic receptors.

Apart from conventional risk factors such as cigarette smoking, obesity, hypertension, diabetes mellitus, hypercholesterolemia, physical inactivity and metabolic syndrome, a family history of coronary artery disease (CAD) seems to be important, especially in young people. Among the genes that may potentially influence the onset and the progression of CAD, there are those controlling the following: renin-angiotensin-aldosterone system (RAAS), adrenergic receptors, paraoxonases, endothelin and nitric oxide synthase. They may modulate the risk of disease onset, as well as its progression and patient prognosis. The unravelling of genetic determinants of CAD may be the first step towards a better understanding of the pathological process involved, the early identification of those at risk and individualizing treatment.

Is polymorphism within eNOS gene associated with the late onset of myocardial infarction? A pilot study.

INTRODUCTION: Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is a potent vasodilator. Several polymorphisms in the eNOS gene have been described, some of them being linked with the increased risk of cardiovascular disease, coronary heart disease (CHD), and coronary spasm. METHODS AND RESULTS: We studied 3 polymorphisms within the gene of eNOS (-786T/C, G10T, and 894 G/T) in patients with their first myocardial infarction (MI) younger than 45 years and in healthy volunteers. We found the relation between the occurrence of eNOS 894G allele and the Gensini score, which describes the severity of CHD (P = .020). CONCLUSIONS: The fact that first clinical manifestation of MI occurred in G carriers when the atherosclerotic plaque was much more advanced than in T carriers may suggest that wild-type genotype provided a better compensatory mechanisms due to NO synthesis and/or release. The polymorphisms within eNOS gene G10T, 894G/T, and -786T/C were not associated with the increased risk of MI.

Role and significance of statins in the treatment of hypertensive patients.

BACKGROUND: Statins are the first-line drug therapy in the treatment of hypercholesterolemia. The beneficial clinical impact of statins on the cardiovascular system results not only from their lipid-lowering action but also from other effects. Recently, it has been suggested that statins can reduce blood pressure, especially in hypertensive patients. AIM: The role of the hypotensive action of statins and other mechanisms which reduce cardiovascular risk in hypertensive patients are discussed in this review. METHODS: Electronic databases searched were [MEDLINE (1966 - February 2009), EMBASE and SCOPUS (1965 - February 2009), DARE (1966 -- February 2009)]. Additionally, abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. The main data search terms were: blood pressure, hypertension, hypercholesterolemia and statins. FINDINGS: At present, it is difficult to unequivocally assess the impact of statins on blood pressure. However, according to most authors, the impact of statins on the decrease in BP is slight, but significant, especially among patients with hypertension.