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Cardiorenal Med [journal]
- RAS-Mediated Adaptive Mechanisms in Cardiovascular Tissues: Confounding Factors of RAS Blockade Therapy and Alternative Approaches. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Dec; 2(4):268-280.
Since the classic experiments by Tigerstedt and Bergman that established the role of renin in hypertension a century ago, aggressive efforts have been launched to effectively block the renin-angiotensin system (RAS). Blockade of RAS is advocated at multiple levels by direct renin inhibitor, angiotensin-converting enzyme inhibitor and/or angiotensin II type 1 receptor blocker, or aldosterone inhibitor (spironolactone), and has now become part of the standard of care to control hypertension and related metabolic diseases including diabetes. However, recent lessons learned from randomized clinical trials question the wisdom of blocking RAS at multiple levels. In this context, it is highly pertinent that components of RAS are evolutionarily conserved, and novel physiological/adaptive/protective roles for renin and angiotensin-converting enzyme are currently emerging. Angiotensin II, the classical RAS effector peptide responsible for hypertension, hypertrophy, fluid retention and fibrosis, manifests its cardiovascular protective effect when it activates the angiotensin II type 2 receptor. Additionally, angiotensin-converting enzyme 2 and the angiotensin II metabolite Ang-(1-7) that acts through the Mas proto-oncogene constitute the cardiovascular and renal protective branch of RAS. It is conceivable that modulating this vasodilative/anti-inflammatory branch of RAS by activation of the RAS components that constitute this branch may offer a safer long-term treatment strategy to balance RAS activity and achieve homeostasis compared to chronic multilevel RAS inhibition.
- Bone Mineral Density as a Predictor of Atherosclerosis and Arterial Wall Stiffness in Obese African-American Women. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Dec; 2(4):328-334.
Bone demineralization is associated with higher cardiovascular event rates, possibly due to vascular calcification and accelerated atherosclerosis. African-Americans have less bone loss and less calcium content within atherosclerotic plaques. However, whether loss of bone mass is related to atherosclerosis has not been examined in African-Americans. The objective of this study was to evaluate possible associations between bone mineral density (BMD), carotid intimal-medial thickness (CIMT), and arterial stiffness. We studied 100 obese African-American women (BMI: 26.6 ± 6.2; age: 63 ± 14 years) referred for BMD estimation by dual-energy X-ray absorptiometry scan. BMD (g/cm(2)) was obtained at the lumbar spine (L1-L4), femoral neck, and total hip. Arterial stiffness was evaluated by the heart rate-corrected augmentation index (AI@75) and pulse wave velocity (PWV) using applanation tonometry. CIMT was measured by vascular ultrasound. Mean CIMT, AI@75, and PWV were 0.72 ± 0.14 mm, 28.8 ± 9.0%, and 8.9 ± 1.6 m/s, respectively. Mean BMD values at the lumbar spine, femoral neck, and hip were 0.96 ± 0.19, 0.80 ± 0.16, and 0.91 ± 0.17 g/cm(2). Older subjects had higher CIMT (r = 0.61, p < 0.001) and AI@75 (r = 0.42, p < 0.001). There was a significant correlation between AI@75 and CIMT (r = 0.45, p < 0.001). BMD was negatively correlated with AI@75 (lumbar: r = -0.22, p = 0.03; femoral neck: r = -0.24, p = 0.01; hip: r = -0.21, p = 0.03). BMD was unrelated to CIMT (lumbar: r = -0.09, p = 0.42; femoral neck: r = -0.15, p = 0.17; hip: r = -0.13, p = 0.23). On multivariate analysis, age (p < 0.001), hypertension (p = 0.02), and lumbar BMD (p = 0.01, R(2) = 0.30) were independent predictors of increased AI@75 after adjusting for age, height, and cardiovascular risk factors. These findings were unchanged upon substitution of femoral neck BMD (p = 0.05, R(2) = 0.28) into the model. There was a trend with hip BMD (p = 0.06, R(2) = 0.28) in the regression model. Age-matched comparison between normal BMD (n = 25) and osteoporotic patients (n = 34) demonstrated a significant difference in AI@75 (26.6 ± 8.9 vs. 31.6 ± 9.1%, p = 0.04). In summary, women with lower BMD had increased arterial stiffness. There was no relationship between BMD and atherosclerosis. In conclusion, age, hypertension, and BMD are independent predictors of higher arterial stiffness. Vascular changes are related to bone mineral loss, suggesting lower BMD may increase cardiovascular risk in African-Americans.
- Phosphoprotein Phosphatase PP2A Regulation of Insulin Receptor Substrate 1 and Insulin Metabolic Signaling. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Dec; 2(4):308-313.
Insulin (INS) metabolic signaling is important for normal cardiovascular and renal function as well as for exerting the classic actions of INS, such as glucose uptake in skeletal muscle tissue. There is emerging evidence that tyrosine phosphatases as well as protein kinases have important modulating roles in INS metabolic signaling in both cardiovascular and classically INS- sensitive tissues. For example, increases in phosphatase activity may partially explain how angiotensin II and aldosterone attenuate activation of the INS receptor substrate protein 1 (IRS-1)-phosphatidylinositol 3 kinase-protein kinase B pathway, thereby promoting INS resistance. On the other hand, phosphatase activation may also exert beneficial and cardiovascular protective effects in conditions such as overnutrition by blocking serine phosphorylation of IRS-1, thereby improving downstream INS metabolic signaling. Both the beneficial and the detrimental effects exerted by the activation of phosphatases will be covered in this report.
- Comorbid Heart Failure and Renal Impairment: Epidemiology and Management. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Dec; 2(4):281-297.
Heart failure mortality is significantly increased in patients with baseline renal impairment and those with underlying heart failure who subsequently develop renal dysfunction. This accelerated progression occurs independent of the cause or grade of renal dysfunction and baseline risk factors. Recent large prospective databases have highlighted the depth of the current problem, while longitudinal population studies support an increasing disease burden. We have extensively reviewed the epidemiological and therapeutic data among these patients. The evidence points to a progression of heart failure early in renal impairment, even in the albuminuric stage. The data also support poor prescription of prognostic therapies. As renal function is the most important prognostic factor in heart failure, it is important to establish the current understanding of the disease burden and the therapeutic implications.
- The Role of Team-Based Care Involving Pharmacists to Improve Cardiovascular and Renal Outcomes. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Dec; 2(4):243-250.
The number of patients with cardiovascular and kidney disease in the United States continues to grow as the population ages, increasing the demand on the health care system and its providers. Many patients develop chronic conditions in which optimization of care is labor intensive, specifically hypertension, hyperlipidemia, diabetes, heart failure, and chronic kidney disease. Therefore, innovative and collaborative approaches to health care are warranted. Several team-based health care models have evolved and are gaining popularity, including the Patient-Centered Medical Home (PCMH) and Medication Therapy Management (MTM). Team-based care is widely supported in the literature, demonstrating significant improvement in cardiovascular and renal outcomes. This article will review the premises of PCMH and MTM, review the evidence and roles for team-based care specific to cardiovascular and renal outcomes, and introduce fundamentals to implement collaborative practice focusing on pharmacist-provider teams.
- Relationship between Plasma Pentraxin-3, Neutrophil-to-Lymphocyte Ratio, and Atherosclerosis in Renal Transplant Patients. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Dec; 2(4):298-307.
BACKGROUND/AIMS:Atherosclerosis and inflammation are the most important risk factors in the pathogenesis of cardiovascular diseases (CVD) in patients with end-stage renal disease (ESRD). Pentraxin-3 (PTX-3) was shown to predict inflammation and atherosclerosis in ESRD patients. However, the role of renal transplantation (Rtx) in terms of atherogenesis is still unclear. We aimed to investigate the relationship between PTX-3, neutrophil-to-lymphocyte ratio (NLR), and carotid intima-media thickness (CIMT) in Rtx patients and healthy controls.
METHODS:This was a cross-sectional study involving 29 Rtx patients (12 females, 40.1 ± 11.9 years) without overt CVD and 19 healthy subjects (9 females, 36.9 ± 8.9 years), testing the relationship between CIMT, assessed by ultrasonography, and selected biomarkers.
RESULTS:CIMT, PTX-3, and high-sensitivity C-reactive protein (hs-CRP) levels of Rtx patients were found to be significantly higher compared to healthy subjects. CIMT was positively correlated with age, creatinine, uric acid, triglyceride, PTX-3, hs-CRP, and NLR, and negatively correlated with estimated glomerular filtration rate in all participants. In Rtx patients, CIMT was positively correlated with age, BMI, serum phosphorus, low-density lipoprotein, and hs-CRP. The multivariate analysis revealed that hs-CRP was found to be an independent variable of CIMT in Rtx patients.
CONCLUSION:Our data showed that inflammation and atherosclerosis persist in Rtx patients. Serum hs-CRP might be a useful marker to assess these parameters in this population.
- Heart Failure Associated with Metastatic Myocardial Calcification in a Hemodialysis Patient with Progressive Calcification of the Hand. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Dec; 2(4):251-255.
Metastatic myocardial calcification is a frequent cause of heart failure in hemodialysis patients. However, early detection is difficult, often resulting in a poor prognosis. A 47-year-old man with hemodialysis-dependent end-stage renal disease presented with progressive dyspnea. Levels of serum phosphate, calcium, and intact parathyroid hormone were poorly controlled. He developed pain in his right thumb 1 year before presentation, and the pain gradually increased and extended to the entire right hand. Hand radiography 1 month earlier had revealed significant progressive calcification. Echocardiography showed severe, diffuse hypokinesis and pericardial effusion as well as possible anterior myocardial calcification with high echogenicity. Chest computed tomography revealed a severely dilated heart with anterior massive myocardial calcification and a large amount of pericardial effusion, which was not detected on computed tomography performed 20 months earlier. The patient was diagnosed with heart failure associated with metastatic myocardial calcification and died suddenly 2 weeks later. This experience suggests that progressive metastatic calcification of the skin and subcutaneous tissue is useful for predicting myocardial calcification.
- Improved Identification and Antihypertension Pharmacotherapy in Cardiorenal Metabolic Syndrome: Focus on Racial/Ethnic Minorities, Olmesartan Medoxomil, and Combination Therapy. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Dec; 2(4):256-267.
Cardiorenal metabolic syndrome (CRS) is a global health care concern in view of aging in certain populations, increased obesity, changing lifestyles, and its close association with type 2 diabetes mellitus and cardiovascular morbidity and mortality. Determining the appropriate criteria for CRS has been somewhat controversial, and efforts to fully describe and define the syndrome are still ongoing. Nonetheless, improving knowledge of the syndrome among health care professionals will help to identify patients who may require pharmacological and therapeutic lifestyle intervention, particularly with regards to addressing high-normal blood pressure and hypertension. This article reviews current clinical guidelines with a focus on the identification, especially in racial/ethnic minorities, treatment, and associated cardiovascular morbidity and mortality of high blood pressure and hypertension in patients with CRS. Efficacy and outcomes studies that provide insight into the selection of an initial antihypertensive regimen in this population will be discussed. Finally, a brief review of the benefits of olmesartan medoxomil and combination therapy and patient factors in the management of hypertension with CRS will be addressed.
- Obesity and the Cardiorenal Metabolic Syndrome: Therapeutic Modalities and Their Efficacy in Improving Cardiovascular and Renal Risk Factors. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Dec; 2(4):314-327.
The prevalence of obesity has increased rapidly in the United States. Obesity affects about one third of the adult population and, even though it is attributed to excess calorie intake and inadequate physical activity, its etiopathogenesis is much more complex and is an area of active study. Lifestyle modifications (with a focus on increased activity and decreased calorie intake) have modest efficacy in the treatment of obesity. There is a dearth of safe and effective therapeutic modalities to treat obesity. In this review, we discuss the role of different treatment options in the management of obesity and its comorbidities, with a focus on recently approved drugs and the emerging role of bariatric surgery.
- Vitamin D and Parathyroid Hormone Relationships with Urinary Nitric Oxide Metabolites and Plasma Isoprostanes in African-Americans. [JOURNAL ARTICLE]
- Cardiorenal Med 2012 Aug; 2(3):234-242.