Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secondary hyperparathyroidism (HPT) is a common complication of chronic kidney disease (CKD) and a frequent cause of clinically significant bone disease. Soft-tissue and vascular calcification, cardiovascular disease, and calcific uremic arteriolopathy (CUA) are additional serious consequences of the disorder that may contribute directly to cardiovascular morbidity and mortality in patients with CKD. Less widely appreciated manifestations include neurological disturbances, hematological abnormalities, and endocrine dysfunction. Secondary HPT arises from alterations in calcium, phosphorus, and vitamin D metabolism that develop early in the course of CKD and become more pronounced as kidney function declines. Treatment is often delayed, however, until the disease is well established. Current therapeutic strategies rely largely on the use of vitamin D sterols to diminish excess parathyroid hormone (PTH) synthesis and to lower serum or plasma PTH levels, but their use is often confounded by increases in serum calcium and phosphorus concentrations, changes that can aggravate soft-tissue and vascular calcification. As such, there is a need for new therapeutic interventions that can effectively lower serum or plasma PTH levels without producing untoward side effects. The current review summarizes the diverse manifestations of secondary HPT in patients with CKD. The consequences of inadequately controlled secondary HPT and the adverse effects of selected therapeutic interventions for the disorder on vascular calcification and cardiovascular disease in those with CKD are discussed.
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PMID:The consequences of uncontrolled secondary hyperparathyroidism and its treatment in chronic kidney disease. 1514 47

The reduction of cardiovascular disease risk in kidney failure involves treatment of modifiable risk factors and provision of proven interventions to patients with established disease. Volume status management is key to blood pressure control. Statins are the agents of choice for the treatment of dyslipidemia. Target hemoglobin levels should be achieved using intravenous iron and erythropoietic agents. Combinations of calcium and noncalcium-containing phosphorus binders and vitamin D and its analogues should be used to attain target parathyroid hormone, phosphorus, and calcium phosphorus product levels. beta Blockers and aspirin are recommended in patients with ischemic heart disease and angiotensin-converting enzyme inhibitors (or angiotensin II receptor blockers), and beta blockers are recommended in patients with heart failure with reduced ejection fraction. In patients who require revascularization, studies suggest a survival benefit of coronary artery bypass graft surgery over percutaneous transluminal coronary angioplasty and coronary artery stenting.
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PMID:Treating the Patient with Kidney Failure to Reduce Cardiovascular Disease Risk. 1521 21

Mortality rates in ESRD are unacceptably high. Disorders of mineral metabolism (hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism) are potentially modifiable. For determining associations among disorders of mineral metabolism, mortality, and morbidity in hemodialysis patients, data on 40,538 hemodialysis patients with at least one determination of serum phosphorus and calcium during the last 3 mo of 1997 were analyzed. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum phosphorus, calcium, calcium x phosphorus product, and intact parathyroid hormone (PTH) using proportional hazards regression. Also determined was whether disorders of mineral metabolism were associated with all-cause, cardiovascular, infection-related, fracture-related, and vascular access-related hospitalization. After adjustment for case mix and laboratory variables, serum phosphorus concentrations >5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and >/=9.0 mg/dl). Higher adjusted serum calcium concentrations were also associated with an increased risk of death, even when examined within narrow ranges of serum phosphorus. Moderate to severe hyperparathyroidism (PTH concentrations >/=600 pg/ml) was associated with an increase in the relative risk of death, whereas more modest increases in PTH were not. When examined collectively, the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperphosphatemia. Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients.
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PMID:Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. 1528 7

Patients with end-stage renal disease have markedly increased risk for death from cardiovascular disease. Renal failure is associated with multiple metabolic and endocrinologic abnormalities, and these alterations are involved in advanced atherosclerosis and high cardiovascular risk. Increased insulin resistance index by homeostasis model assessment (HOMA-IR), a simple index of insulin resistance, was an independent predictor of cardiovascular mortality in nondiabetic patients on maintenance hemodialysis. Renal failure impairs lipoprotein metabolism leading to the atherogenic lipoprotein profile characterized by increased triglyceride-rich remnant lipoproteins such as intermediate-density lipoprotein, an independent factor of increased aortic stiffness. Non-high-density lipoprotein cholesterol, the sum of cholesterol of intermediate-density lipoprotein and other apoB-containing lipoproteins, is an independent factor associated with increased arterial thickness and a predictor of cardiovascular death in hemodialysis patients. The risk for cardiovascular death in hemodialysis patients is associated closely with hypertension and malnutrition, but not with obesity. The constellation of insulin resistance, dyslipidemia, hypertension, and malnutrition in renal failure suggests the presence of another type of metabolic syndrome promoting cardiovascular disease. In addition, vitamin D deficiency and abnormalities in calcium, phosphate, and parathyroid hormone levels increase the death risk from cardiovascular disease in renal failure. It is expected that treatment of these metabolic and endocrinologic alterations would improve the survival of patients with renal failure.
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PMID:Roles of metabolic and endocrinological alterations in atherosclerosis and cardiovascular disease in renal failure: another form of metabolic syndrome. 1549 Apr 3

Cardiovascular disease in association with coronary artery calcification (CAC) is the leading cause of death in patients with end-stage renal disease (ESRD). The evaluation of CAC has been performed by electron beam CT scan. The purpose of the present study was to assess CAC using multi-detector spiral CT (MDCT) and to evaluate contributors to CAC in these patients. Fifty-three patients on chronic hemodialysis participated in this study. Their mean age was 61.0+/-9.6 years, and the mean duration of dialysis therapy was 6.7+/-5.4 years. We used an automatic device to measure arterial pulse wave velocity (PWV) as an index of arterial wall stiffness. The aortic calcification index (ACI) was quantified morphometrically by CT scan. The CAC score correlated positively with ACI score (r =0.863, p <0.0001). Linear regression analysis indicated that the CAC scores correlated positively with age (r =0.406, p =0.0023), C-reactive protein (r =0.38, p =0.0047) and PWV (r =0.303, p =0.0271). Stepwise regression analysis indicated that ACI (beta-coefficient=0.862, p <0.0001) and arterial PWV (beta-coefficient=0.303, p <0.0001) were independently associated with CAC score. The mean CAC score of patients with cardiac events (2,568.5+/-2,575.1 mm3) was significantly higher than that (258.0+/-409.2 mm3) of patients without cardiac events. In conclusion, our results showed clearly that assessment of CAC score using MDCT may be predictive for detecting the presence of coronary artery disease. CAC is indirectly associated with increased arterial stiffness and the extent of aortic calcification in hemodialysis patients. We did not find a significant correlation between CAC score and parameters of mineral metabolism, including serum levels of calcium, phosphorus and parathyroid hormone. A longitudinal prospective study is required to assess the predictive value of this technique in determining cardiac events in large numbers of hemodialysis patients.
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PMID:Assessment of coronary artery calcification in hemodialysis patients using multi-detector spiral CT scan. 1549 70

Vitamin D3 plays a key role in regulating calcium and mineral homeostasis in support of normal development and maintenance of bone. The classic effects of vitamin D3 include promoting absorption of dietary calcium in the gut and, through its actions as a steroid endocrine hormone, regulating the synthesis and secretion of parathyroid hormone. The effects of the vitamin D3 system are mediated through the highly regulated generation of the potent, active metabolite 1,25-dihydroxyvitamin D3 (calcitriol). Vitamin D3 exerts its effects through the vitamin D3 receptor (VDR), a ligand-activated nuclear receptor expressed in a wide array of tissue and cell types. Studies performed in mice rendered deficient for VDR suggest that calcitriol and VDR may inhibit the renin-angiotensin system and reduce blood pressure in the long-term. Clinical studies suggest that administration of vitamin D3 analogs produces differential benefit with regards to mortality in dialysis patients; other studies suggest that vitamin D3 analogs may provide cardiovascular benefit in both dialysis and nondialysis patients. This paper reviews clinical and preclinical studies, which suggest that vitamin D3 analogs may provide therapeutic utility in the treatment of cardiovascular disease independent of those mechanisms typically associated with the vitamin D3 endocrine system.
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PMID:Vitamin D analogs: novel therapeutic agents for cardiovascular disease? 1550 49

The most important step in calcium homeostasis is the regulation of parathyroid hormone (PTH) secretion. The discovery and characterization of the calcium sensing receptor (CaR) of the parathyroid cell has led to a better understanding not only of the physiology of the parathyroid glands, but also of the development of hyperparathyroidism. Drugs acting on CaR can now be designed to treat hyperparathyroidism and osteoporosis. The workshop on primary hyperparathyroidism held at the National Institutes of Health in 2002 has recommended new guidelines for the treatment of asymptomatic hyperparathyroidism. Controversy still exists regarding the treatment of patients with non-classical symptoms, such as weakness, fatigue and depression. Primary hyperparathyroidism as a risk factor for cardiovascular disease and mortality is also debated. Improved techniques for the preoperative localization of pathological parathyroid glands have led to a shift in surgical strategy: surgeons abandon the traditional bilateral neck exploration in favor of a more limited approach. This change of strategy has not been based on the results of prospective randomized studies and the long term results are not known.
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PMID:Primary hyperparathyroidism. Update on pathophysiology, clinical presentation and surgical treatment. 1565 69

Animal studies suggest that calcium-phosphorus homeostatic abnormalities cause cardiovascular disease in uremia; few observational studies in humans have explored this. Associations in the retrospective United States Renal Data System Waves 1, 3, and 4 Study of 14,829 patients who were on hemodialysis on December 31, 1993, were examined. Mean age and duration of renal replacement therapy were 60.0 and 3.2 yr, respectively; 40.7% had diabetes. Quintiles (Q(1) to Q(5)) of (albumin-adjusted) calcium were </=8.7, 8.8 to 9.2, 9.3 to 9.6, 9.7 to 10.2, and >10.2 mg/dl; phosphorus, </=4.4, 4.5 to 5.3, 5.4 to 6.3, 6.4 to 7.5, and >7.5 mg/dl; calcium-phosphorus product, </=40.9, 41.0 to 50.1, 50.2 to 59.2, 59.3 to 71.0, and >71.0 mg(2)/dl(2); and parathyroid hormone (PTH), </=37, 38 to 99, 100 to 210, 211 to 480, and >480 pg/ml. Higher calcium levels were associated with fatal or nonfatal cardiovascular events (adjusted hazards ratio, 1.08 for Q(5), versus Q(1)) and all-cause mortality (Q(2), 1.07; Q(4), 1.11; Q(5), 1.14). Phosphorus levels were associated with cardiovascular events (Q(2), 1.06; Q(3), 1.13; Q(4), 1.14; Q(5), 1.25) and mortality (Q(4), 1.10; Q(5), 1.19), calcium-phosphorus product was associated with cardiovascular events (Q(3), 1.09; Q(4), 1.14; Q(5), 1.24) and mortality (Q(4), 1.09; Q(5), 1.19), and PTH levels were associated with cardiovascular events (Q(5), 1.12) and mortality (Q(5), 1.17). Despite limitations (including retrospective design; noncurrent study era; and lack of serial calcium, phosphorus, and PTH measurements), this study suggests that disorders of calcium homeostasis are associated with fatal and nonfatal cardiovascular events and all-cause mortality in hemodialysis patients.
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PMID:Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: the USRDS waves 1, 3, and 4 study. 1587 82

Vitamin D3 is modified by vitamin D3-25-hydroxylase in the liver, and 25-hydroxyvitamin D3-1alpha-hydroxylase in the kidney, to form the active metabolite, 1,25-dihydroxyvitamin D3. Chronic kidney disease (CKD) is characterized by reduced synthesis of 1,25-dibydroxyvitamin D3, inadequate renal phosphate clearance and calcium imbalance, secondary hyperparathyroidism (SHPT) and bone disease. CKD patients encounter a much higher risk of cardiovascular disease (CVD) than the general public. The cardiovascular risk factors for CKD patients include conventional factors such as age, gender, hypertension, diabetes, dyslipidemia and smoking, and non-conventional factors, such as anemia, uremia, reduced vascular compliance, inflammation and various hormonal factors. Several vitamin D analogs are currently available for the treatment of SHPT, and recent clinical data show that these analogs provide survival benefit for CKD patients in the order of paricalcitol > calcitriol > no vitamin D analog, independent of parathyroid hormone and calcium. Moreover, the survival benefit seems to be associated with cardiovascular causes. The observations made from these clinical studies raised intriguing questions about the involvement of the vitamin D receptor locus (VDR) in the cardiovascular system. This review discusses recent data regarding the role of vitamin D and its analogs in the CVD associated with CKD.
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PMID:Cardiovascular disease in chronic kidney failure: is there a role for vitamin D analogs? 1581

Patients with primary hyperparathyroidism (PHPT) have increased risk of cardiovascular disease. For patients undergoing preoperative parathyroid imaging with 99mTc-sestamibi single photon emission computed tomography (SPECT), we combined cervical SPECT and gated cardiac SPECT to achieve information about the localization of parathyroid adenomas, myocardial perfusion, and the left ventricular ejection fraction (LVEF) at rest. A series of 22 patients with PHPT and no history of myocardial infarction or angina pectoris were recruited consecutively. At 60 minutes after injection of 700 MBq 99mTc-sestamibi, SPECT of the neck and gated myocardial perfusion SPECT were performed at the same time. All of the patients who underwent parathyroidectomy had the parathyroid adenoma localized as predicted from the SPECT. Five patients (23%) had myocardial perfusion defects extending more than 15% (range 15-25%), and they had higher plasma parathyroid hormone levels (p = 0.03), and lower LVEF (p = 0.007) than patients without perfusion defects. We suggest that patients with hyperparathyroidism and suspected cardiovascular disease can undergo 99mTc-sestamibi parathyroid SPECT simultaneously with gated myocardial perfusion SPECT to obtain information about the resting perfusion status and cardiac systolic function. The results from myocardial perfusion SPECT can lead to initiation of cardiovascular treatment and eventually perioperative precautions.
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PMID:Myocardial perfusion defects and the left ventricular ejection fraction disclosed by scintigraphy in patients with primary hyperparathyroidism. 1595 36


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