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Chapter 19. Cardiovascular Disease in Chronic Kidney Disease
Nadia Zalunardo, MD, FRCPC; Adeera Levin, MD, FRCPC
Zalunardo N, Levin A. Zalunardo N, & Levin A Zalunardo, Nadia, and Adeera Levin.Chapter 19. Cardiovascular Disease in Chronic Kidney Disease. In: Lerma EV, Berns JS, Nissenson AR. Lerma E.V., & Berns J.S., & Nissenson A.R.(Eds.),Eds. Edgar V. Lerma, et al.eds. CURRENT Diagnosis & Treatment: Nephrology & Hypertension. McGraw Hill; 2009. Accessed January 29, 2023. https://accessmedicine.mhmedical.com/content.aspx?bookid=372&sectionid=39961156
Zalunardo N, Levin A. Zalunardo N, & Levin A Zalunardo, Nadia, and Adeera Levin. (2009). Chapter 19. cardiovascular disease in chronic kidney disease. Lerma EV, Berns JS, Nissenson AR. Lerma E.V., & Berns J.S., & Nissenson A.R.(Eds.),Eds. Edgar V. Lerma, et al. CURRENT Diagnosis & Treatment: Nephrology & Hypertension. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=372&sectionid=39961156
Zalunardo N, Levin A. Zalunardo N, & Levin A Zalunardo, Nadia, and Adeera Levin. "Chapter 19. Cardiovascular Disease in Chronic Kidney Disease." CURRENT Diagnosis & Treatment: Nephrology & Hypertension Lerma EV, Berns JS, Nissenson AR. Lerma E.V., & Berns J.S., & Nissenson A.R.(Eds.),Eds. Edgar V. Lerma, et al. McGraw Hill, 2009, https://accessmedicine.mhmedical.com/content.aspx?bookid=372&sectionid=39961156.
Cardiovascular disease (CVD) is highly prevalent among patients with chronic kidney disease (CKD) and is the most common cause of death in this population.
The manifestations of CVD in CKD are variable and include left ventricular hypertrophy, ischemic heart disease, heart failure, and peripheral vascular disease.
Traditional and nontraditional (or "uremia-related") cardiac risk factors are common in CKD.
Clinicians should maintain a high index of suspicion for the presence of CVD in patients with CKD, even when the presentation is atypical.
An aggressive approach to diagnosis and treatment of CVD is recommended in patients with CKD.
CVD is highly prevalent among patients with CKD and is the most common cause of death in this population. Importantly, patients with impaired kidney function are more likely to die than to progress to end-stage renal disease (ESRD) requiring renal replacement therapy and those who do reach dialysis have a staggering mortality rate of about 20% per year. In dialysis patients of all ages, the mortality rate from CVD far exceeds that observed in the general population (Figure 19–1). Dialysis has the greatest impact on younger patients, whose mortality rate from CVD is more than 100 times greater than that of their counterparts with normal kidney function.
Cardiovascular disease mortality for patients on dialysis, by age, gender, and race, in comparison to the general population. (Reproduced with permission from Foley RN et al: The clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32:S112.)
The burden of CVD begins to accumulate long before patients reach ESRD. For example, left ventricular (LV) hypertrophy (LVH) increases in prevalence with declining renal function and is present in 75% of patients beginning dialysis treatment. Ischemic heart disease (IHD) and heart failure also develop early, and are present in 40% and 35% of incident dialysis patients, respectively. Recent publications have demonstrated a profound impact of a reduced glomerular filtration rate (GFR) below 60 mL/minute on cardiovascular event rates.
In recent years both the National Kidney Foundation (NKF) and the American Heart Association (AHA) have recommended that patients with CKD be placed in the highest risk group for the development of CVD. However, while recognition of their high-risk status has improved, evidence from clinical trials evaluating the benefit of interventions aimed at reducing CVD risk in the CKD population is still largely lacking.
Recommendations by the NKF for the evaluation and treatment of CVD in dialysis patients were published in April 2005. The key to these guidelines is the recommendation that an aggressive approach to diagnosis and treatment is warranted in patients with ESRD due to the high risk of CVD in this patient group.
The spectrum of CVD in CKD is wide, and includes abnormalities of the heart and blood vessels, such as LVH, congestive heart failure (CHF), valvular heart disease, pericarditis, cardiac arrhythmias, IHD, and peripheral vascular disease (PVD). Those disorders that are most common and account for the majority of the morbidity and mortality in patients with CKD will be the focus of this chapter: LVH, IHD, heart failure, and PVD. In this chapter, the term CKD is used generically to refer to patients with all degrees of kidney dysfunction, including those on dialysis. Comments pertaining to a particular subgroup of patients (for example, predialysis patients or ESRD patients) are specified as such.
Go AS et al: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296. [PubMed: 15385656]
Keith DS et al: Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004;164:659. [PubMed: 15037495]
Kidney Disease Outcomes Quality Initiative (K/DOQI) Group: K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005;45(4 Suppl 3):S16. [PubMed: 15806502]
Manjunath G et al: Level of kidney function as a risk factor for cardiovascular outcomes in the elderly. Kidney Int 2003;63:1121. [PubMed: 12631096]
Sarnak MJ et al: American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;108:2154. [PubMed: 14581387]
Cardiovascular Risk Factors in Chronic Kidney Disease
Traditional and nontraditional risk factors have been discussed in the literature as contributors to the high rate of CVD in CKD (Table 19–1). Certainly, traditional cardiac risk factors are highly prevalent in these patients. These include advanced age, diabetes mellitus, hypertension, low high-density lipoprotein (HDL), and LVH. However, the complexity of the relationship between some traditional cardiovascular risk factors and overall mortality in ESRD must be appreciated. For example, a "reverse epidemiology" or "U-shaped" mortality curve has been observed whereby ESRD patients with low cholesterol and low blood pressure paradoxically have an increased mortality. This increase in mortality is hypothesized to reflect underlying malnutrition and/or inflammation (in the case of low cholesterol) and advanced cardiomyopathy (in the case of low blood pressure). Thus, the benefits of strategies traditionally used to combat CVD in the general population, such as lowering of cholesterol and blood pressure, may be questioned in the setting of kidney disease.
Table 19–1. Traditional and Nontraditional Cardiovascular Risk Factors in Chronic Kidney Disease.
Traditional risk factors
Nontraditional factors
Older age
Albuminuria
Lipoprotein (a) and apo (a) isoforms
Higher LDL cholesterol
Lipoprotein remnants
Lower HDL cholesterol
Abnormal calcium/phosphate metabolism
Extracellular fluid volume overload
Physical inactivity
Electrolyte imbalance
Family history of cardiovascular disease
Inflammation (C-reactive protein)
Left ventricular hypertrophy
Thrombogenic factors
Altered nitric oxide/endothelin balance
LDL, low-density lipoprotein; HDL, high-density lipoprotein.
Reproduced with permission from Sarnak MJ et al: American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;108:2154.
Furthermore, there is accumulating evidence that a reduced GFR per se is an independent risk factor for CVD. It may be that lower GFR is associated with, or marks for, nontraditional or "uremic" risk factors. These nontraditional risk factors, outlined in Table 19–1, include anemia, abnormalities of calcium and phosphate metabolism, inflammation, prothrombotic factors, oxidative stress, and perhaps also hyperhomocysteinemia, and elevated levels of lipoprotein (a). However, despite strong associations between these factors and CVD in epidemiologic studies, a causal relationship has not been proven, nor have interventional studies been conducted that demonstrate changes in outcomes with treatment of these abnormalities.
In patients with residual kidney function (ie, those not yet on dialysis), the issue of proteinuria and cardiovascular risk merits specific comment. First, microalbuminuria is associated with an increased risk of cardiovascular events in both diabetic and nondiabetic subjects, even in the absence of renal insufficiency. While patients with microalbuminuria often have an increased prevalence of traditional cardiac risk factors, it is also thought that microalbuminuria may be a marker of generalized endothelial dysfunction or inflammation. Second, individuals with the nephrotic syndrome are known to have an increased risk of myocardial infarction (MI). Among the potential explanations for this are that hyperlipidemia, hypercoagulability, and hypertension are common in the nephrotic syndrome and these may contribute to the increased risk of IHD. In addition, recent publications describe clear associations between proteinuria and increased rates of CVD at all levels of kidney dysfunction.
Given the documented burden of CVD in CKD, the association with adverse outcomes in patients where the two coexist, and the biologically plausible explanations as to the impact of traditional and nontraditional risk factors in CKD populations, it is important for the practicing clinician to understand the complexity of this area, what is known and where gaps in our knowledge base exist.
The work performed by the LV in each cardiac cycle is equal to the product of the ventricular pressure and stroke volume. In kidney disease, the work of the LV is increased due to both pressure and volume overload. Hypertension, arteriosclerosis, and aortic stenosis contribute to pressure overload, while volume overload occurs as a result of factors such as anemia, increased extracellular fluid volume, and the presence of arteriovenous fistulas. These and potentially other factors, such as hyperparathyroidism and the "uremic milieu," contribute to the development of LVH, an independent risk factor for mortality in all CKD patients, independent of dialysis status.
The LVH that occurs intitially as an adaptive response to physiologic stimuli (pressure or volume) eventually becomes maladaptive. At the cellular level, the metabolically active myocytes begin to experience an energy deficit, partly due to ischemia, resulting in cell death. In addition, cardiac fibroblasts proliferate, expanding the extracellular matrix of the myocardium and causing myocardial fibrosis. From a functional point of view, the hypertrophied ventricle becomes stiff, impairing relaxation and resulting primarily in diastolic dysfunction, at least initially. These changes may partially explain the high prevalence of heart failure in this patient group.
Heart failure is common in CKD and is present in about one-third of incident dialysis patients. Patients may have systolic dysfunction, diastolic dysfunction, or both. The pathogenesis of heart failure is multifactorial with contributions from LVH, IHD, valvular heart disease, and other abnormalities specific to the uremic state such as chronic extracellular fluid volume expansion, disturbances in divalent ion metabolism, anemia, and the presence of arteriovenous (AV) fistulas.
Vascular Disease: Atherosclerosis and Arteriosclerosis
There are two general types of arterial vascular disease in CKD: Atherosclerosis and arteriosclerosis. Atherosclerosis is a disease of the intima and is characterized by plaques and vessel occlusion. The most common vessels affected are the medium-sized arteries, such as the coronary, femoral, and carotid arteries. There are many contributors to atherosclerosis, including the high prevalence of cardiac risk factors such as advanced age, dyslipidemia, hypertension, and the metabolic syndrome.
Patients with CKD also have a high prevalence of arteriosclerosis, or stiffening of the arteries; this may occur in the presence or absence of significant atherosclerosis. Although it normally occurs with aging, the process appears to be accelerated in kidney disease. The intima and media of the large, elastic arteries such as the aorta and the common carotid are affected in particular. The vessel wall is remodeled and becomes thickened and stiff, reducing compliance. These stiff vessels contribute to hemodynamic changes, including an increase in systolic blood pressure, a decrease in diastolic blood pressure, and as a result, a widened pulse pressure and increased pulse wave velocity. The raised systolic blood pressure increases LV afterload and contributes to the development of LVH, while the reduced diastolic pressure compromises coronary artery perfusion and contributes to myocardial ischemia. Recent data from both dialysis and predialysis patients have confirmed the association among an elevated pulse pressure, a clinical manifestation of arterial stiffness, and adverse outcomes.
A contributor to the arterial stiffening in kidney disease that has recently been given some attention is calcification of the intimal and medial layers of these vessels. It has been observed that this calcification is a key feature of the arterial disease in CKD, especially in ESRD. The calcification is more extensive and is observed much earlier in ESRD than in the general population. Abnormalities of bone mineral metabolism, including elevations in serum phosphorus, calcium, and calcium × phosphorus product, among other factors, are intimately involved in promoting vascular calcification.
This unique contribution of specific factors to arterial calcification and measured arterial stiffness, in conjunction with anemia (also common in CKD), may explain in part the high prevalence of CVD in CKD patients.
Giachelli CM: Vascular calcification: in vitro evidence for the role of inorganic phosphate. J Am Soc Nephrol 2003;14(9 Suppl 4):S300. [PubMed: 12939385]
Giachelli CM: Vascular calcification mechanisms. J Am Soc Nephrol 2004;15:2959. [PubMed: 15579497]
London GM: Cardiovascular calcifications in uremic patients: clinical impact on cardiovascular function. J Am Soc Nephrol 2003;14(Suppl 4):S305. [PubMed: 12939386]
London GM: Cardiovascular disease in chronic renal failure: pathophysiologic aspects. Semin Dial 2003;16:85. [PubMed: 12641870]
Moe SM et al: Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels. Kidney Int 2003;63:1003. [PubMed: 12631081]
LVH may be asymptomatic or patients may present with diastolic dysfunction, which is discussed in further detail in the next section.
On physical examination, hypertension is common. Particular attention should be paid to the pulse pressure as a surrogate measure of arterial stiffness, where "normal values" are <40–60 mm Hg. Precordial palpation may reveal a left ventricular heave and a sustained and diffuse cardiac apical impulse. On auscultation, a fourth heart sound may be heard.
Due to the lack of sensitivity of symptoms and physical examination findings, echocardiography is usually used for diagnosis and clinical follow-up of patients with LVH.
Heart failure may occur as a result of systolic dysfunction, diastolic dysfunction, or both. It may be asymptomatic or patients may present with shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, reduced exercise tolerance, and progressive extracellular fluid volume expansion. In addition, patients with LV dysfunction on hemodialysis often tolerate dialysis treatments poorly and episodes of intradialytic hypotension may occur.
On physical examination, the signs of heart failure include pulmonary vascular congestion such as jugular venous distention and crackles due to pulmonary edema. LVH is the most common cause of diastolic dysfunction in CKD and these patients would be expected to have the cardiac findings discussed under that section. However, findings in patients with predominantly systolic heart failure include cardiomegaly, manifested by an inferiorly and laterally displaced apical pulsation, and the presence of a third heart sound on auscultation.
Due to the insensitivity of the physical examination, echocardiography is usually used for the diagnosis of heart failure. In addition to evaluating left ventricular function and geometry, echocardiography also has the advantage of providing other useful information, such as the presence of valvular heart disease, which may also contribute to left ventricular dysfunction.
The main symptom of cardiac ischemia is angina, which may be accompanied by symptoms of CHF. In CKD, the high proportion of patients with a concomitant diagnosis of diabetes mellitus means that atypical presentations of cardiac ischemia, such as shortness of breath without chest pain, may occur. In addition, patients with CKD may experience episodes of silent cardiac ischemia. For example, asymptomatic ST segment depression has been observed during hemodialysis treatments.
Findings on physical examination of acute cardiac ischemia may be relatively few. Signs of left and/or right heart failure may be observed depending on the size and location of the vascular territory affected. In general, the diagnosis of an acute coronary syndrome (ACS) relies on laboratory findings, including serial cardiac enzyme determinations and an electrocardiogram (ECG).
In the CKD population, a number of factors may interfere with the timely diagnosis of IHD, including diabetes, atypical presentations, and the relative lack of utility of specific tests in dialysis patients. Thus, a high index of suspicion in patients at high CVD risk is imperative.
PVD, also a result of the atherosclerotic process, is common in CKD. The symptoms and signs depend on the vascular territory affected. Carotid artery disease causes neurologic changes during a transient ischemic attack or stroke. When the arteries supplying the lower extremities are affected, intermittent claudication with exertion may result. However, given the poor tolerance to exercise in the CKD population in general, this symptom probably lacks sensitivity. Chronic ischemia of the legs results in skin changes, hair loss, and muscle atrophy. Other signs include pallor, reduced or absent pulses, and bruits. Without treatment, skin ulceration and gangrene can occur when ischemia becomes critical.
The key to the diagnosis of PVD is serial assessment of peripheral arterial function through clinical examination and laboratory investigations. Reluctance to evaluate PVD in a timely manner may have led to an increase in morbidity and mortality in this particular cohort of patients.
Laboratory Findings
Cardiac Troponins
Troponins comprise part of the contractile apparatus of myocytes in both cardiac and skeletal muscle. They consist of three subunits: Troponin C, troponin T, and troponin I. While cardiac and skeletal troponin C are identical, cardiac troponin T (cTnT) and I (cTnI) are encoded by genes different from their skeletal counterparts, and the molecules are also different. The assays currently in use for detection of cTnT and cTnI are specific for troponin released from the heart muscle. They are also highly sensitive to even small amounts of myocardial damage. The degree of troponin elevation in patients presenting with a suspected ACS provides important prognostic information, even in the presence of renal dysfunction. For these reasons, cTnT and cTnI are the preferred markers for the diagnosis of acute cardiac injury.
Interpretation of cardiac troponin concentration in the setting of ESRD is complicated by the fact that the levels, particularly of cTnT, may be elevated in apparently asymptomatic individuals. The reasons for elevations in troponin in the absence of cardiac symptoms and the significance of the levels are still debated, but the finding of an elevated troponin concentration in a patient with ESRD cannot necessarily be dismissed as a false-positive result even if unaccompanied by cardiac symptoms.
What is even less clear is why asymptomatic troponin elevations in ESRD are observed more frequently with cTnT than with cTnI. Proposed explanations for this include differences in release patterns from damaged cardiac myocytes, circulating half-life, and dialyzability, in addition to the particular characteristics of the assays themselves.
Despite these controversies and uncertainties, patients with renal failure suspected of having an ACS should be followed with serial cardiac troponin assessments. A troponin level rising over time suggests an acute injury, especially if accompanied by other cardiac symptoms or ECG changes. A positive but unchanging level may not indicate acute damage, but it has prognostic implications in ESRD patients nonetheless. On the other hand, obtaining serial "normal" or "negative" results has an excellent negative predictive value and is therefore useful for excluding an ACS.
Cardiac Imaging Studies
All patients suspected of having an ACS should be evaluated with an ECG. However, the interpretation can be complicated by preexisting abnormalities on the baseline tracing. In the absence of acute cardiac ischemia, ST-T segment morphology can be altered by LVH, electrolyte disturbances, and medications such as digoxin. In a patient presenting with possible cardiac ischemia, obtaining an old ECG for comparison can be extremely helpful. Aside from abnormalities of the baseline study, ischemic changes are expected to have an appearance the same as in individuals without kidney disease.
Exercise Treadmill Testing
In screening for coronary artery disease (CAD), detection of exercise-induced ischemia with exercise treadmill testing is of limited utility in renal failure. Patients are often unable to attain their target heart rate for reasons that include poor exercise tolerance, autonomic neuropathy, and use of medications that impair the chronotropic response to exercise, such as β-blockers and calcium channel blockers. Abnormalities of the resting ECG further compromise the sensitivity and specificity of this test. For these reasons, pharmacologic stress testing is generally preferred in renal failure.
Two-dimensional echocardiography has multiple uses in the renal failure population. It can be used to assess for abnormalities of cardiac structure, such as LVH and valvular heart disease, and also provides a good estimate of systolic and diastolic LV function. Ideally, patients on dialysis should be as close to their estimated dry weight as possible at the time of this study or at least have studies performed at the same time in their dialysis cycle for comparison purposes.
Dobutamine stress echocardiography (DSE) can be used as a noninvasive screening test for ischemic heart disease. Studies in the renal failure population are limited in number and comparisons between studies are difficult because of inconsistencies in methodology. Overall, DSE appears to be a useful, but imperfect, screening test for CAD in CKD.
Nuclear Scintigraphy
Nuclear scintigraphy has uses similar to echocardiography in patients with kidney disease: Assessment of ventricular function, screening for CAD, and prediction of future cardiac events.
To screen for myocardial ischemia, a radionuclide is injected and fixed or reversible perfusion defects are detected by comparing cardiac single-photon emission computed tomography (SPECT) images at rest and following stress (exercise or pharmacologic). Dipyridamole is a pharmacologic agent that acts by blocking the cellular reuptake of adenosine, thereby increasing its levels and causing vasodilation. In patients with markedly impaired kidney function, baseline levels of adenosine are increased, thus a reduced vasodilatory response to exogenously administered dipyridamole may occur, thereby potentially producing a false-negative result.
Several studies have evaluated the use of nuclear scintigraphy in patients with renal failure; however, the reported results are variable, likely due to inconsistencies in methodology. Like DSE, nuclear scintigraphy appears to be a moderately useful but suboptimal screening test for CAD in this group of patients.
Both thallium scintigraphy and DSE have prognostic implications in the renal failure population. In a recent meta-analysis of these myocardial perfusion studies for stratifying cardiac risk among patients with ESRD who were candidates for kidney or kidney–pancreas transplantation, compared to patients with negative test results, patients with positive tests had a relative risk of myocardial infarction of 2.73 and of cardiac death of 2.92 following transplantation.
Currently, there is no literature to guide the choice between nuclear scintigraphy and DSE in screening for CAD in CKD, as there are no studies directly comparing the two modalities. Therefore, it is reasonable to consider local expertise, availability, and cost to guide test selection.
Computerized Tomography Scanning
Electron beam computerized tomography (EBCT) and helical CT scanning methods can be used to assess the degree of coronary artery calcification (CAC). In the general population, where calcification occurs in the intima in association with atherosclerotic deposits, CAC scores have been found to correlate with angiographic plaque burden and to predict future cardiac events. However, their utility in CKD populations is less clear.
Vascular calcification of both the intimal and medical layers is common in renal failure. The CAC scores of ESRD patients in particular are often several times greater than those found in the general population. However, CT scanning cannot distinguish between intimal and medial calcification, and there are conflicting reports as to whether there is a correlation between CAC scores and atherosclerotic plaque burden. Furthermore, while data demonstrate an association between higher CAC scores and mortality in ESRD, debate still exists as to the utility of this test in routine clinical care or as an endpoint in clinical trials. Until the appropriate long-term and interventional studies are undertaken, CT scanning is not recommended as a screen for CAD in the CKD population.
Percutaneous Coronary Angiography
While IHD is most commonly a result of atherosclerotic CAD, a substantial proportion of patients with CKD experience cardiac ischemia without significant coronary artery stenosis. It is likely that these patients, particularly those with LVH, have microvascular insufficiency that limits myocardial perfusion and causes ischemia.
The gold standard for diagnosis of CAD is angiography; however, the cost and the potential for morbidity make it impractical as a screening test. In general, it is reserved for patients whose noninvasive screening tests are positive, those who present with an ACS, or those with known CAD who have developed recurrent symptoms despite optimal management.
In predialysis patients, angiography may worsen renal function by causing contrast nephropathy or cholesterol embolization. Invasive examinations should be undertaken only after careful consideration of their necessity, and whether the results will alter patient management. Contrast nephropathy generally produces a transient and reversible decline in renal function and in the modern era, with low osmolality contrast dyes, improved technology, and some evidence of renoprotective effects of specific agents, the risk may be lower than previously described. On the other hand, the decline in renal function caused by cholesterol emboli is usually permanent and can render patients with earlier stages of CKD dialysis dependent.
In general, the initial approach to investigating PVD is with noninvasive testing, as is done in the general population. An ankle–brachial index (ABI)(at rest plus or minus postexercise) is a simple test that can be performed in the physician's office to confirm the suspicion of PVD. An ABI of <0.90 suggests PVD and further investigations with segmental limb pressures, plethysmography, and various ultrasound techniques or magnetic resonance angiography are indicated.
Conventional angiography is generally performed in patients with significant ischemia as part of the workup for a revascularization procedure in suitable candidates.
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LVH is an independent predictor of morbidity and mortality in patients with ESRD. LV growth begins early in CKD and is associated with a number of potentially modifiable risk factors, such as anemia and hypertension. Partial regression of LVH has been associated with reduced mortality in observational studies, but randomized studies have yet to convincingly demonstrate this. It may be that primary prevention of LVH by earlier treatment of risk factors is a better approach; however, there is a paucity of randomized data supporting this as well. The following sections will outline the current evidence for the prevention and treatment of LVH with a focus on treatment of anemia and hypertension.
In observational studies, declining hemoglobin, particularly <10–11 g/dL, is associated with the development of LVH and increased cardiovascular mortality. Uncontrolled studies have also shown that treatment of anemia is associated with partial regression of LVH and reduced mortality. Unfortunately, the data available from randomized controlled trials are less convincing. Although quality of life and exercise capacity certainly improve, there is no conclusive evidence that hemoglobin levels >10–11 g/dL improve LVH and other important clinical outcomes such as cardiovascular events and mortality.
Early randomized trials focused on the progression of LV structural abnormalities in the ESRD population with preexisting asymptomatic cardiac disease. The findings suggest that normalization of hemoglobin does not lead to regression of established LVH; however, prevention of LV dilation may occur with normalization of hemoglobin.
The predialysis population has also been evaluated for changes in cardiac dimensions with treatment of anemia. At the end of the 2-year follow-up period in the major study in this regard, there was no difference between the two groups with respect to the primary outcome, change in LVMI. It has been hypothesized that perhaps the development and progression of LVH were not clearly affected because the actual observed difference in hemoglobin between the two groups was relatively small. However, another study with a similar design demonstrated similar findings: A lack of change in LVMI with control of hemoglobin and other parameters. Additional clinical trials are ongoing to further explore the effects of various degrees of anemia correction on cardiac structure in CKD patients not yet on dialysis.
In the general population with essential hypertension, lowering blood pressure is associated with a regression of LVH. A meta-analysis evaluating the relative efficacy of various antihypertensive agents found that the reduction in LVMI was greatest with angiotensin II receptor blockers (ARBs), followed by angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. Diuretics and β-blockers were least effective. In addition, it has recently been shown that ARBs can reduce the myocardial fibrosis observed in LVH, indicating that these medications have a direct effect on the myocardium, beyond their ability to lower blood pressure.
Data are limited in kidney disease, but some small studies support regression of LVH when hypertension is treated with pharmacologic inhibition of the rennin–angiotensin–aldosterone system (RAAS), although this has not been an entirely consistent finding. In most studies, it is difficult to ascertain how much of the effect is due to blood pressure reduction per se and how much is related to a specific effect of RAAS blockade. Nonetheless, because of the clinical and basic science evidence demonstrating that ACE inhibitors and ARBs are associated with delay of progression of kidney disease and fibrotic processes as well as other cardiovascular benefits, they are recommended as first-line antihypertensives in the CKD population.
Finally, blood pressure control has been associated with regression of LVH in observational studies of hemodialysis patients receiving either nocturnal or short daily hemodialysis compared to standard three times weekly hemodialysis.
Primary Prevention
There have been few randomized controlled trials conducted in the CKD population addressing primary prevention of ischemic heart disease. In addition, elevated serum creatinine is often a criterion for exclusion from interventional studies of the general population, which further contributes to the scarcity of data in patients with kidney disease. Nonetheless, given that CKD patients are in the highest risk group for development of CVD, it seems reasonable to apply the same general treatment recommendations applied for other patients at similar CV risk. This includes lifestyle modification, such as smoking cessation, exercise, and maintenance of ideal body weight. Glycemic control in diabetic patients and treatment of hypertension to a target blood pressure of <130/80 mm Hg (<140/90 mm Hg predialysis in hemodialysis patients) are also recommended by the Kidney Disease Outcomes Quality Initiative (K/DOQI) group for CV risk reduction in CKD.
Aspirin has been recommended for primary prevention of myocardial infarction in the general population when CVD risk is high. However, these recommendations are based on the CV benefits outweighing the risk of major (intracranial or gastrointestinal) bleeding events. Although individuals with CKD have a propensity for bleeding, in the recently published First United Kingdom Heart and Renal Protection (UK-HARP-1) Study only an increased risk of minor, not major, bleeding episodes was observed with use of low-dose aspirin in CKD. However, patients with severe renal failure, who would be expected to be at highest risk of bleeding complications, represented a minority of patients in this study. Well-conducted clinical trials in heterogeneous populations of both dialysis and predialysis populations need to be conducted before aspirin can be adopted into clinical practice on a routine basis.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) appear to be safe and effective in reducing LDL cholesterol levels in renal failure; however, the evidence regarding their benefit in CKD populations is conflicting, particularly in primary prevention of CVD.
From subgroup and post hoc analyses, it appears that statin therapy may be of benefit in primary prevention in patients with mild to moderate CKD. While these analyses are encouraging, it is difficult to draw firm conclusions without corroborative data from well-designed prospective studies.
In fact, one prospective randomized trial of statin therapy for primary prevention of CVD in kidney transplant recipients yielded somewhat less optimistic results with the use of Lescol in renal transplant patients.
Data from ongoing prospective trials should help to clarify the question of whether statin use is of benefit in primary prevention of CVD in CKD. Until data from these studies become available, recommendations for treatment of dyslipidemia are taken from trials performed in the general population and summarized in K/DOQI guidelines for the treatment of dyslipidemias. As for other very high risk patients, treatment to a target LDL of <100 mg/dL (2.59 mmol/L) is recommended. The potential benefit of even further reductions in LDL levels has not yet been evaluated in CKD.
Although there are some reports that CKD increases the risk of statin toxicity, recently published studies do not confirm this. An initial dose reduction is generally recommended in severe renal failure (creatinine clearance <10 mL/minute) and caution is required in renal transplant recipients given the potential for drug interactions that may result in increased toxicity.
CKD patients presenting with an ACS should be managed in the same way as the general population, recognizing that patients with severe renal insufficiency have generally been excluded from most trials of therapy. There are some important caveats with respect to the use of low-molecular-weight heparin (LMWH) and GPIIb-IIIa antagonists in CKD. Unlike unfractionated heparin, the clearance of LMWH is primarily renal, therefore elimination is slower and less predictable, and bleeding complications may be increased. Thus, unfractionated heparin is generally preferred in patients with significant renal insufficiency. There are some reports of an increased risk of bleeding with the use of GPIIb-IIIa antagonists; however, their use is still generally recommended in appropriate individuals. Dose adjustments may be necessary for some of the preparations as their excretion is partially renal.
Because of a lack of evidence specific to the renal failure population, patients with CKD should receive the same secondary prevention measures employed in the general population. This includes lifestyle modification (smoking cessation, exercise, and maintenance of ideal body weight), aspirin, β-blockers, statins, ACE inhibitors, and revascularization procedures in suitable candidates.
Anemia can contribute to exercise-induced ischemia and exacerbation of angina in CKD. The target hemoglobin currently recommended by K/DOQI is 11–12 g/dL in patients with IHD. While there may be theoretical benefits to achieving a "normal" hemoglobin level, one well-known prospective randomized study in hemodialysis patients with a history of IHD or CHF showed that a more normal hematocrit (˜40%) was associated with an increased risk of nonfatal MI and death compared to the group with a lower target hematocrit (˜30%).
Coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is sometimes necessary in suitable candidates with CAD. When CKD patients are compared to the general population with CAD, patients with renal failure are more likely to experience postprocedure hemorrhagic complications, and they have higher rates of in-hospital mortality as well as poorer long-term survival with both PCI and CABG. In addition, PCI restenosis rates appear to be increased with angioplasty alone, but are likely improved if accompanied by stenting. The role of drug-eluting stents in renal failure is not yet well known. Finally, while there are no prospective randomized studies guiding the choice of revascularization method in CKD, a retrospective analysis of data from the United States Renal Data System (USRDS) favors CABG over PCI in dialysis patients, particularly in those with diabetes. Ideally, prospective studies are needed to answer this question.
In general, the decision for revascularization must be individualized and assessed on a case-by-case basis. Unfortunately, current decision making often reflects a pervasive therapeutic nihilism on the part of the general medical community toward patients with renal failure, which may lead to a postponement of testing and interventions and ultimately adversely impact the long-term outcomes of this group of patients.
The two variants of heart failure, diastolic and systolic, can coexist in patients with CKD. Those CKD patients with predominantly diastolic heart failure often have significant LVH. In this case, attention should be focused on potentially modifiable contributing factors, which include hypertension and anemia.
Systolic heart failure has been studied extensively in the general population, but much less so in CKD patients. Thus studies in the general population are the only basis upon which to guide treatment in CKD. Salt restriction and diuresis are the mainstays of therapy to attain euvolemia. While loop diuretics are the diuretics of choice, a thiazide may be added to potentiate diuresis in resistant patients. Drug dose modification is often necessary in those with GFR <60 mL/minute. The dose of loop diuretics must often be increased while medications that rely on renal excretion, including certain β-blockers (eg, atenolol) and digoxin, require a dose reduction. Close follow-up is required for potentially dangerous complications that may be more common in CKD, such as hyperkalemia with the use of ACE inhibitors, ARBs, or aldosterone antagonists, and cardiac toxicity with digoxin. In addition, sotalol has been recognized as a particularly problematic antiarrythmic in CKD patients and should probably be avoided.
While patients with CKD are underrepresented in studies of heart failure, recent observational studies seem to indicate that patients with CHF and mild to moderate CKD derive a mortality benefit from medications including ACE inhibitors and β-blockers.
Finally, while correction of anemia to a target of 11–12 g/dL is important, current evidence suggests that further normalization of hemoglobin may be associated with adverse outcomes, at least in hemodialysis patients with CHF.
PVD is a significant source of morbidity in CKD patients. The medical management of PVD generally focuses on treatment of cardiovascular risk factors such as sedentary lifestyle, smoking, diabetes, hypertension, and dyslipidemia. Revascularization, either with percutaneous intervention or with bypass surgery, is often required and amputations are common.
Given that calcification is a key feature of the vascular pathology of CKD, attempts to reduce this should theoretically be of benefit in attenuating the progression of vascular disease. This is currently an area of active research. Perhaps rigorous attention to bone mineral metabolism and maintenance of appropriate levels of serum calcium, phosphorus, and parathyroid hormone through judicious use of calcium and non-calcium-containing phosphate binders, vitamin D, and calcimimetics will attenuate the progression of vascular calcification and improve clinical outcomes in CKD.
Baigent C et al: Study of Heart and Renal Protection (SHARP). Kidney Int Suppl 2003;84:S207. [PubMed: 12694346]
Baigent C et al: First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. Am J Kidney Dis 2005;45:473. [PubMed: 15754269]
Ciulla MM et al: Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: results of a randomized trial. Circulation 2004;110:552. [PubMed: 15277331]
Coletta AP et al: Clinical trials update from the European Society of Cardiology Heart Failure meeting: SHAPE, BRING-UP 2 VAS, COLA II, FOSDIAL, BETACAR, CASINO and meta-analysis of cardiac resynchronisation therapy. Eur J Heart Failure 2004;6:673. [PubMed: 15302018]
Frank H et al: Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients. Kidney Int 2004;66:832. [PubMed: 15253740]
Furuland H et al: A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients. Nephrol Dial Transplant 2003;18:353. [PubMed: 12543892]
Holdaas H et al: Assessment of Lescol in Renal Transplantation (ALERT) Study Investigators. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003;361:2024. [PubMed: 12814712]
Kidney Disease Outcomes Quality Initiative (K/DOQI) Group: K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis 2003;41(4 Suppl 3):S1. [PubMed: 12671933]
Kidney Disease Outcomes Quality Initiative (K/DOQI): K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004;43(5 Suppl 1):S1. [PubMed: 15114537]
McAlister FA et al: Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study. Circulation 2004;109:1004. [PubMed: 14769700]
McMahon LP et al: Slimheart Investigators Group. Development, prevention, and potential reversal of left ventricular hypertrophy in chronic kidney disease. J Am Soc Nephrol 2004;15:1640. [PubMed: 15153576]
Pinkau T et al: Coronary revascularization in patients with renal insufficiency: restenosis rate and cardiovascular outcomes. Am J Kidney Dis 2004;44:627. [PubMed: 15384013]
Roger SD et al: Effects of early and late intervention with epoetin alpha on left ventricular mass among patients with chronic kidney disease (stage 3 or 4): results of a randomized clinical trial. J Am Soc Nephrol 2004;15:148. [PubMed: 14694167]
Suzuki H et al: Comparison of the effects of angiotensin receptor antagonist, angiotensin converting enzyme inhibitor, and their combination on regression of left ventricular hypertrophy of diabetes type 2 patients on recent onset hemodialysis therapy. Ther Apher Dial 2004;8:320. [PubMed: 15274684]
Tonelli M et al: Veterans' Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) Investigators. Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency. Kidney Int 2004;66:1123. [PubMed: 15327407]
Tonelli M et al: Effect of pravastatin on cardiovascular events in people with chronic kidney disease. Circulation 2004;110:1557. [PubMed: 15364796]
Wanner C et al: Deutsche Diabetes-Dialyse-Studie (4D) Study Group. Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis (4D study): demographic and baseline characteristics. Kidney Blood Press Res 2004;27:259. [PubMed: 15316128]
The prognosis for CKD patients with CVD is uniformly poor. The mortality rate of dialysis patients is an astounding 20% per year, with CVD representing the most common cause. LVH is an independent risk factor for mortality in ESRD. Declining GFR is associated with increased mortality following an acute myocardial infarction. In a recent study, patients with an estimated GFR >75 mL/minute had a 3-year mortality rate from MI of 14% compared to almost 46% in patients with an estimated GFR <45 mL/minute. The outcome for patients with CHF and/or PVD in conjunction with lower GFR is also much worse than that observed in the general population.
The evidence base for treating CVD in CKD is far from complete. However, it now appears that patients with concurrent CKD and CVD likely benefit from many of the interventions implemented in individuals with CVD alone. In addition, most of these interventions can be used safely with appropriate monitoring in the CKD setting. Nonetheless, it has been consistently demonstrated that patients with CKD are less likely to receive these potentially beneficial therapies than their counterparts with normal kidney function. This has been termed "therapeutic nihilism" by some and may represent a further contribution to the poor outcomes observed with CVD in CKD.
In summary, CVD in patients with CKD is prevalent, and is likely due to a combination of both traditional and nontraditional risk factors. These factors are present to variable extents and for varying durations over the lifespan of patients with reduced GFR, and their effects are likely multiplicative rather than additive. Current data describing methods of investigation and treatment fail to give adequate direction to physicians caring for patients throughout the entire spectrum of CKD. Nonetheless, this chapter attempts to synthesize the current state of knowledge, identify gaps in the evidence base, and describe reasonable strategies based on the data available.
Given the increasing recognition of CKD as a risk factor for CVD, ongoing trials will need to explore more completely the mechanisms by which lower GFR or dialysis therapies impact the natural history of CVD. Therapeutic strategies will then be evaluated in the context of a more complete understanding of the complexity of this disease.
Anavekar NS et al: Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 2004;351:1285. [PubMed: 15385655]


text:
The Observer endorses Blais-Shewit
Observer Editorial Board | Monday, February 6, 2017
When polls open Wednesday morning, the Notre Dame student body will be faced with a difficult decision between two highly qualified student government tickets — juniors Becca Blais and Sibonay Shewit and juniors Rohit Fonseca and Daniela Narimatsu. Both teams developed thoughtful and considerate platforms that addressed the concerns and needs of the student body.
The Observer Editorial Board interviewed each ticket over the weekend and — having considered the priorities and plans of each ticket — voted to endorse Blais-Shewit.
The Blais-Shewit platform dreams big — perhaps too big at points — but overall has done an excellent job of assessing the current needs of the Notre Dame student body. Their commitment to the notion of "flipping the model" of student government — that is, bringing student government to the students instead of requiring students to come to student government with their concerns — is clear, as much of their platform is derived from ideas they have received from the student body itself. They pledge to "represent every student," and while this sometimes leads to too many unattainable ideas, they demonstrate a passion for understanding the student body. The Blais-Shewit ticket also boasts a remarkable and prominent amount of student government experience — particularly as Blais currently serves as student body vice president and Shewit served as secretary and later chief of staff for the Ricketts-Ruelas administration — and it is evident they have a concrete grasp on its inner workings. The focus on clear and tangible goals is a large part of what makes the Blais-Shewit ticket stand out, and while the two have ambitious plans for the coming year, the fact that they have a wide range of well-defined and formulated ideas is encouraging.
However, our endorsement comes with several reservations about the ticket. While Blais and Shewit have a thorough platform addressing the varied needs of the student body, we have some concerns about its feasibility. Although most individual items on the ticket's platform are achievable in their own right, the more than 100 individual goals Blais and Shewit put forward on their platform present perhaps too gargantuan a task to accomplish in one term. We are concerned the team may be taking on too much, which could distract and detract from some of their larger goals. More to the point, we fear this ambition could lead to should-be achievable objectives failing due to resources being spread too thin.
Additionally, some ideas on the Blais-Shewit platform — for example, "ensuring all campus buildings are 100 percent handicap accessible, and fight for necessary changes for those that are not" — are simply not attainable. Last spring, The Observer found nearly half of all dorms on campus were not wheelchair accessible, and fixing all of them would require significant funding and construction to add elevators and ramps. Likewise, decreasing the number of tests given between Thanksgiving and finals week and extending Flex Points to Eddy Street stores seem both unlikely and beyond the scope of what student government can reasonably achieve. While we appreciate the ticket's attempt to address a wide variety of issues, we found the scope of the ticket's platform misleading in terms of what they could realistically expect to accomplish.
A few ideas have also made a repeat appearance from Blais's campaign last year with current student body president Corey Robinson, leading us to question why they weren't achieved this year and whether it is feasible to achieve them in the coming year. Specifically, part of Blais' platform last year focused especially on getting Sexual Assault Nurse Examiners (SANE) in St. Liam's. However, it has yet to be achieved and has landed back on the Blais-Shewit agenda this year. While Robinson and Blais made progress on implementing this initiative in the past year, we still have doubts about whether it will come to fruition this time around.
On the other hand, the Fonseca-Narimatsu ticket takes the opposite approach of focusing almost exclusively on what they can reasonably hope to accomplish in one year with existing resources and shying away from offering many new ideas — ultimately limiting themselves in their goals and plans. For example, in addressing sexual assault — a key issue on campus — they failed to provide any new ideas to tackle the problem, and pledged to work with the University to make public the results of the Campus Climate Survey — results which are already made public. Other initiatives put forward by the ticket focus solely on education about available resources, which is certainly helpful, but left us wondering what more could be done.
We did appreciate the team's commitment to improving mental health awareness on campus: Their plans to work with the McDonald Center for Student Well-Being and to promote Irish State of Mind Week demonstrated a dedication to the mental health of the student body, an issue we take seriously. Further, their combined experience throughout a variety of student government committees and other organizations is an asset to their understanding of the Notre Dame student body, but we felt it did not stack up against that of the Blais-Shewit ticket.
While the Fonseca-Narimatsu ticket proposes an interesting idea with the concept of RouND Tables — a regular campus event giving students from different perspectives and groups a forum to discuss divisive tops — we had concerns about both its implementation and the ultimate goal. The plan as is does not address how the ticket plans to attract active participants, particularly those who are not already politically active and vocal on campus, and a large-group discussion may not be the best forum for discussing some of the issues they had in mind.
Finally, we also took notice of each ticket's priorities. Blais and Shewit made it clear both in their platform and the student body debate Monday night that sexual assault and student safety are their primary concerns, whereas Fonseca and Narimatsu, though they do address both safety and sexual assault in their platforms, chose the need for civil discourse as the campaign's primary pillar. While we as a newspaper staff appreciate the need for civil discourse as well, we consider student safety and sexual assault issues that need immediate attention and focus.
So, despite our reservations, the Editorial Board felt most of Blais and Shewit's ideas were sound, pertinent and likely to have a positive impact on the student body. Furthermore, the Blais-Shewit ticket attempts to truly make progress on issues that matter to students, instead of just accepting things as they are.
Tags: blais-shewit, fonseca-narimatsu, Student government, Student government elections
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The Observer endorses Olivia LaMagna and Rohan Andresen
Saturday afternoon, The Observer Editorial Board interviewed the three tickets campaigning for student body...
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redpajama_set_name: RedPajamaCommonCrawl


Park at the 20 car White Oak Trail parking area on Weakley Hollow Rd.
This hike has some of the most spectacular waterfalls in the Shenandoah National Park. Combining two out-and-back hikes, White Oak Canyon & Cedar Run, this loop starts at the bottom of the valley and cuts over near the top of the ridge. With five major falls, numerous smaller cascades and pools, this circuit hike is one of the best.
Begin up the blue blazed White Oak Canyon (WOC) Trail, at the top of the upper parking area next to the SNP ranger station. Shortly cross a steel footbridge, then arrive at the intersection of the Cedar Run Trail that will be your return route. Stay straight on the WOC Trail as it winds to the right, then crosses another steel footbridge over WOC Run.
Follow the blue blazed trail on the right side of WOC Run reaching the WOC/Cedar Run Connector Trail in 0.6 miles. Stay straight on the right side of WOC Run for another 0.7 miles, cross a small stream, then arrive the base of the first set of major falls.
The trail will now make several switchbacks as the grade gets steeper, then reaches the second set of falls in 0.6 miles. Again, the trail will switchback several times, then become less steep, and arrive at a concrete marker for the base of the main WOC falls. To see the falls from the base, follow the side trail straight for 100 yards. Continue uphill on the WOC Trail as it steeply climbs the last 0.1 miles to the main WOC falls overlook.
Continuing uphill from the main overlook, and shortly arrive at the yellow blazed Bridge Path Trail that comes in from the right. Stay straight, then cross WOC Run in another 40 yards at the horse rail. If WOC Run is high, continue up the right side of WOC Run and cross a footbridge in 120 yards.
After crossing the run follow the wide yellow blazed WOC Fire Road/Horse Trail. In 1.6 miles the WOC Fire Road/Horse Trail will veer right. Stay left on the narrower yellow blazed trail, marked on a concrete post as "Horse Tr To Big Meadows". In 0.6 miles the horse trail intersects the blue blazed Cedar Run Trail.
Turn left downhill on the blue blazed Cedar Run Trail, then in 1.3 miles cross Cedar Run. In 0.2 miles after crossing Cedar Run reach the top set of main falls at Halfmile Cliff known as "The Slide". 60 yards below the main falls is a pool where Cedar Run passes through a narrow gorge.
Continue downward on the Cedar Run Trail for 0.5 miles where the blue blazed trail makes a sharp left to cross Cedar Run for the last time. After crossing Cedar Run follow the trail for 0.3 miles to the intersection of the WOC/Cedar Run Connector Trail. Turn right downhill on the Cedar Run Trail towards RT600, and in 0.4 miles arrive back at the WOC Trail intersection. Turn right, re-cross the steal footbridge, and arrive back at the parking area.
Parking lot was at 10:15am when we arrived. We ended up parking at the private overflow lot and paid the guy $10. There were two cars there at the lot when we arrived. So you might luck out with a free spot before 10. This like old rag now where you have to pay $10 to park in the overflow lot.
There's no White Oak Canyon loop on the free map so we ended up hiking all the way up and down the Appalachian trail back to Cedar Run instead of taking the shortcut across using the fire road to Cedar Run. Wife was not too happy about my poor research on this hike.
The water were strong and high during our hike. We had to wade over the river at multiple places. Our hiking boots were wet from it. We should have taken it off.
The views were pretty nice but I enjoyed the waterfalls on the cedar run side more.
I hadn't hiked the full circuit in a long time, having done a bunch of WOC out-and-backs with the family and dog. I hiked the full circuit for the first time 40 years ago and I wanted to see if I still had it in me. The WOC falls and rock tumbles were spectacular because of all the recent rains. As previous reviewers have stated, the Cedar Run trail was very rocky, steep and difficult and not as well maintained as the WOC trail. I would characterize it as a "primitive trail" for about 2 miles of the descent. The two Cedar Run crossings were challenging due to the high water. I took off my shoes and stumbled and slipped across one crossing and found a fallen tree to use for the second crossing. If you want to do the full circuit I would recommend going up the Cedar Run trail and coming down the White Oak Canyon trail. Having said, that it was a great hike and, yes, I still had it in me.
Did this with Boy Scouts with full packs. This is a challenging circuit hike and would not recommend for young scouts, i.e., less than 14 and not with full packs. Beautiful hike, but do it as a day hike with light packs.
Make no mistake about it, this is a great hike. Scenery is tremendous. Today there was a fog/mist storm on the ridge that blanketed the mountain to create a neat affect. Love it.
However, be aware that going down Cedar Run! At stretches I was fighting for every step. Between boulders, rocks and roots, on the steep incline, the going was slow. Good balance is must.
Next time I will do an out and back on White Oak.
My friend and I hiked this today. The falls are spectacular!! We took our dogs and they loved it, too. We hiked counterclockwise up the WOC trail, saw all the beautiful falls (which, btw, are abundant, deep, and flowing wildly, because of all the rains), crossed the falls via the bridge and continued on the Fire Rd. This was the only part, at the time, that seemed a bit boring to me. But, boy oh boy, by the time we'd hit the Cedar Run trail, we were begging to be back on the Fire Rd. The going was tough coming down. Wear your waterproof hiking boots and watch your steps carefully. Also, take a bathing suit, water shoes, and a picnic. About half way down we had a hard time finding the trail marking. My friend finally found it....across a huge section of falls, clear on the other side. We waded across very carefully. It was not an easy feat with two dogs. We continued the long hike down over rough rocks and boulders. In order to reach the parking lot we had to cross the falls again, in even deeper water! Yes, it was strenuous coming down, but, wow, SO worth it. This has become one of my favorite hikes ever. Do it now before the water lowers! You'll be so glad you did.
Waterfalls, waterfalls, waterfalls! This has to be the most spectacular waterfall hike in Shenandoah National Park. With three sets of falls on the way up White Oak Canyon and three smaller falls heading down Cedar Run, this circuit is among the mid-Atlantic's most popular. Lots of company on the trail.
Usually, the ideal time for this hike is in early spring, but with the rain we've had in the last month, all the falls were near their best. The wildlife was also out; we came across several black snakes, this guy (vid) was a local celebrity with hikers on Saturday, and we also saw a juvenile black bear on the trail.


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redpajama_set_name: RedPajamaGithub


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Conservative Victory on AP US History Framework? Not So Fast
Dr. Susan Berry
Last week, Danniel Henninger, deputy editor of The Wall Street Journal's editorial page, cited recent changes the College Board made to the Advanced Placement U.S. History (APUSH) framework as a "victory" for conservatives. Experts on the framework, however, think that is quite a stretch.
Henninger asserts in his editorial that the College Board – which is led by its president, David Coleman, known to many as the "architect" of the Common Core Standards – has ditched its left-wing bias in its APUSH framework as a result of conservative backlash, an outcome Henninger describes as "an important political event."
In May of 2014, Breitbart News contributors Jane Robbins, senior fellow of American Principles Project, and retired APUSH teacher Larry Krieger wrote about the College Board's replacement of the traditional framework with one in which "George Washington gets one brief mention; other founders, such as Benjamin Franklin and James Madison, none."
"The Declaration of Independence is referred to in passing in one clause of one sentence," they continued. "The redesigned Framework inculcates a consistently negative view of American history by highlighting oppressors and exploiters while ignoring the dreamers and innovators who built our country."
As Henninger aptly describes, the College Board's APUSH framework "read like a left-wing dream. Obsession with identity, gender, class, crimes against the American Indian and the sins of capitalism suffused the proposed guidelines for teachers of AP American history."
However, Henninger seems overwhelmed with the changes made this year by Coleman's team.
"The College Board delivered on its promise," he writes. "The new guidelines, which convey an understanding of American history to thousands of high-school students, are about as balanced as one could hope for."
His announcement that the left-wing "tilt" in the guidelines has "vanished," and that the rewritten framework is now "almost a model of political fair-mindedness," is very much an overstatement to those who have been warning Americans about the dangers of liberal indoctrination of the nation's young people and its consequences for the nation itself.
As Henninger notes, Stanley Kurtz, senior fellow at the Ethics and Public Policy Center and contributing editor to National Review Online, has pressed for competition to the College Board, which has enjoyed a monopoly on the APUSH. Fears over calls for other testing companies to come up with an APUSH framework likely have led the College Board to make some changes that can be perceived as having responded to the conservative outcry.
Kurtz tells Breitbart News that while he agrees the APUSH battle is one of the few that has put the left on the defensive, the left-wing "tilt" of the framework has not "vanished."
"I emphatically disagree that the recently revised AP U.S. history framework is a true victory for conservatives," Kurtz states. "Yes, the College Board has removed the most biased phrases from the framework, and even thrown in a brief good word or two about the free enterprise system. But the changes are largely cosmetic."
Kurtz continues:
The framework remains focused on trendy leftist themes like gender identity and environmentalism, rather than traditional themes like military or diplomatic history. More important, AP U.S. history textbooks and course syllabi have already been conformed to the controversial 2014 framework. There are no plans to change them again. Even if there were, there are really no significant changes to be made since the new framework simply removes a few controversial statements and does not insert fundamentally new themes. The real intentions of the College Board are revealed by the brand new AP European history framework, which shares all the leftist biases of the original 2014 AP U.S. history framework.
Similarly, Peter Wood, president of the National Association of Scholars (NAS), explains that while he understands some want to declare a "conservative victory," he views whatever changes the College Board made only as "a battle won in a long war."
"The College Board played this beautifully," Wood tells Breitbart News, and continues:
It made lots of conspicuous concessions of the sort that would persuade many smart, observant people that APUSH had been restored to mainstream ideas and good historical judgments. Dan Henninger is not alone in declaring it a conservative victory. There are also liberal and centrist academic historians (e.g. KC Johnson) who are breathing a big sigh of relief. And it is telling that historians who are on the radical left are upset that their 2014 APUSH victory has been snatched back.
Wood said he spoke to Coleman before the College Board released its latest APUSH revision.
"I want to give credit where credit is due," he said, adding,
The College Board went through the whole 2014 document and attempted to scrub the political tendentious phrases, the silly identity-politics-style posturing, the sneers directed at conservatives and traditionalists, and the wild imbalance between favored progressive themes and disfavored traditional themes.
"But, unfortunately, there is a lot more to fixing the problem than this," Wood asserts, citing, as Kurtz did, the problem that the standards are part of a larger initiative that includes the AP examinations, the textbooks, and teacher instruction.
"None of those other things have been changed," Wood emphasizes. "That means the students taking APUSH are going to be tested on the 2014 standards. The new 2015 standards are, at least for the next several years, window-dressing."
The problem is not much different from what has taken place with the Common Core standards initiative, and the method is likely one that Coleman borrowed from his experience in developing the nationalized reform, one that has grown tremendously unpopular even while it remains ingrained in public school classrooms.
Proponents of the Common Core initiative frequently demean its opponents, arguing Common Core is "just standards" and nothing more. In fact, the Common Core is far more than standards: it includes federally funded tests aligned with the standards, expensive textbooks and instructional materials, teacher training and rigid guidelines, massive student data collection, and teacher evaluation based on student performance on the tests aligned with the standards.
In states where the Common Core "standards" have been "repealed," replacement standards are often little more than carbon copies or "rebrands" of Common Core. Similarly, some states, like Wisconsin, allow school districts to choose whatever standards they like – except that the required state standardized test is still aligned to the Common Core, making it highly unlikely that school districts would change out their entire curriculum and textbooks for other standards when their students will still be assessed based on the Common Core test.
How can Coleman and the College Board, then, really wipe far-left ideology out of the APUSH when the examinations students take, their textbooks, and the training their teachers receive still are operating under it?
"The only lasting solution to this problem is the creation of a company, advised by top traditionalist scholars, that can compete directly with the College Board," argues Kurtz. "The College Board is desperately afraid of such competition, and such changes as it has made are only efforts to avoid that threat."
"If we make the mistake of prematurely declaring victory, we will kill off the chance to restore true intellectual competition and local choice to education," he adds. "And once the College Board is secure in its monopoly, it will be completely in the control of the leftist professors who already advise it and determine its basic direction."
EducationPoliticsAdvanced Placement U.S. HistoryCollege BoardCommon CoreCommon Core rebrandCommon Core testsDavid Colemanliberal indoctrinationStanley Kurtz


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Q: The best XMLEditor available I am using an old version of Altova's XMLSpy and it often freezes. Do you know an alternative XMLEditor (free or not, web or windows) that I could use to write XML documents based on a XSD file?

A: I can recommend Oxygen XML Editor.

A: I love XML Spy too, even if it is pricey.
I can also recommend Liquid XML.
http://www.liquid-technologies.com/

A: I still love XMLSpy. But Microsoft's XML notepad isn't half bad.

A: Definitely Altova's XMLSpy - It's the best around!
Plus, if you have a support and maintenance package from them, you get free updates (they realease a new version/service pack 3-4 times per year with new features).

A: I use Emacs with PSGML mode, and it does the job quite nicely. Setting things up and getting it all working can be challenging, but Emacs is widely used, very robust, and (with the right expertise) quite extensible. Plus, both Emacs and the PSGML mode package are open source.

redpajama_set_name: RedPajamaStackExchange


text:
Il Progetto Crisalide (Chrysalis Project) è un programma eugenetico segreto dell'universo fantascientifico di Star Trek. È iniziato nel 1960, condotto da un gruppo di genetisti e di biochimici al fine di creare una super-razza, i Potenziati, che avrebbe dovuto dominare l'intero pianeta Terra.

Il progetto
Il Progetto Crisalide era una consorzio privato che godeva di piena autonomia da ogni forma di controllo da parte delle autorità di governo.

Il suo quartier generale si trovava nel deserto di Thar, nascosto sotto le rovine di un'antica fortezza di Rajput.
Grazie alla sua ubicazione, il progetto poté proseguire nel più completo isolamento e la sua esistenza non venne mai conosciuta dagli umani, neppure quando a causa di esso scoppiarono le Guerre Eugenetiche.

Gli scopi
Gli scienziati credevano che creando embrioni umani geneticamente superiori il mondo sarebbe diventato migliore.
Tuttavia un mondo migliore richiedeva che vi vivessero anche individui migliori.
Essi pensavano infatti che individui come Albert Einstein o Martin Luther King fossero il prodotto dell'ambiente e dell'ereditarietà: da qui la necessità della manipolazione genetica, che avrebbe fatto scomparire per sempre mali come le guerre, la povertà, le malattie.

Per ottenere questo, tuttavia, occorreva che una nuova umanità, il cui programma genetico contenuto nel DNA sarebbe stato potenziato, prendesse possesso della Terra.

L'ingegneria genetica
La scienza tradizionale asseriva che fosse possibile clonare un ovocita solo due volte prima che esso diventasse inutilizzabile.

Usando tecniche riproduttive molto al di sopra degli standard del tempo, la dottoressa Sarina Kaur, direttrice del progetto, riuscì invece a clonare molte volte uno stesso ovocita.

Il processo iniziava stimolando una "super ovulazione" nelle donne volontarie (comprese le stesse scienziate che lavoravano al progetto). Gli ovociti così ottenuti venivano quindi trattati introducendo frammenti di DNA specializzato, quindi venivano ottenute più copie di uno stesso ovocita.
In seguito gli ovociti venivano fecondati artificialmente e tenuti in incubatrice ad una temperatura di 37 °C.
Poco dopo la fecondazione gli embrioni venivano esaminati per scoprire eventuali difetti o anomalie genetiche; gli embrioni non utilizzabili venivano scartati.

Questo trattamento era finalizzato ad ottenere miglioramenti nel metabolismo, nell'intelligenza, nel sistema respiratorio e cardiaco e nella muscolatura. Essi riuscirono a creare così una nuova specie: i Potenziati.

I Potenziati

Ora si trattava di consegnare il pianeta ai superuomini.
Per far ciò gli scienziati iniziarono a compiere studi sulla guerra biologica.
Il loro intento era quello di liberare sulla Terra uno streptococco modificato geneticamente, capace di divorare i tessuti molli dell'organismo in brevissimo tempo.

Per infettare l'intero globo si procurarono dei missili ICBM equipaggiati con testate bionucleari.

Essi tuttavia non avevano fatto i conti col fatto che, come scrisse uno degli scienziati aderenti al Progetto Crisalide prima di essere assassinato da un Potenziato, "Una capacità maggiore crea anche un'ambizione maggiore": i Potenziati iniziarono a combattersi tra loro per avere il dominio assoluto sulla Terra, provocando sia le guerre eugenetiche (1992-1996) sia la terza guerra mondiale nel 2026.

La fine del progetto
Benché il conflitto fosse ormai terminato, l'umanità continuò ad avere paura degli esseri geneticamente modificati fino al XXIV secolo.

Nel XXI secolo la Terra mise al bando l'ingegneria genetica in quanto anti-umana, ad eccezione della riparazione delle malattie genetiche gravi.
Tuttavia nel 2130 il genetista Arik Soong rubò alcuni degli embrioni conservati alla Cold Station 12.
L'intento di Soong era lo stesso dei suoi predecessori: migliorare l'umanità eliminando le malattie.
Soong però era convinto di riuscire ad evitare che i Potenziati si comportassero come i loro predecessori avevano fatto.
Il suo piano però fallì miseramente: la natura aggressiva dei Potenziati prese ancora una volta il predominio ed essi iniziarono ancora una volta ad incitare gli umani alla guerra provocando nuovi eccidi di massa.

La missione dell'astronave Enterprise di dare la caccia e distruggere i superuomini rimasti portò all'uccisione dei Potenziati e alla distruzione della maggior parte degli embrioni clonati. (Star Trek: Enterprise: Terra di confine, Stazione 12, I Potenziati).
Alcuni embrioni però caddero nelle mani dei Klingon che, credendo che gli umani stessero cercando di migliorare la loro specie nell'intento di conquistare l'impero Klingon, tentarono di usare il DNA ricavato dagli embrioni per fare la stessa cosa.
Il risultato finale fu la mutazione di un virus altamente contagioso che causò forti cambiamenti
nell'aspetto fisico, nella struttura biologica e nella personalità di molti Klingon (Star Trek: Enterprise: Il virus letale, Divergenze).
Si pensa che alcuni gruppi abbiano conservato le conoscenze riguardanti il modo di migliorare le razze attraverso l'ingegneria genetica e che queste siano ancora reperibili al mercato nero.

Organizzazioni di Star Trek
Organizzazioni segrete immaginarie
Star Trek: Enterprise

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