Long-standing Hypertension Research Articles

Caseous calcification of the mitral annulus

A 71-year-old woman with long-standing hypertension was referred for cardiological evaluation because of dyspnea on exertion, orthopnea, and orthostatic dizziness. On physical examination, a /6 systolic murmur was heard at the apex of the heart. She had no clinical signs of heart failure. There were no pulmonary rales. Transthoracic echocardiography showed pronounced concentric hypertrophy of the left ventricle with normal ejection fraction. Additionally, a large tumor attached to the posterior mitral annulus causing impairment of transmitral left ventricular inflow was visible. This tumor moved the mitral leaflet apparatus more anteriorly toward the left ventricular outflow tract resulting in systolic anterior motion (SAM) of the mitral valve leaflets with variable left ventricular outflow tract obstruction of up to 50 mm Hg. The diagnosis of caseous calcification of the mitral annulus was made (fig. 1). The patient underwent surgical resection of the tumor. The wall of the tumor was incised, a toothpaste-like mass was evacuated from a slightly calcified coat (fig. 2A), and the wall of the collapsed tumor was adapted with a running suture. The normal morphology and competence of the mitral valve could be preserved. Grossly, the lesion consisted of gray-white to yellow necrotic debris, resembling caseous

Insulin-like growth factor-1 elevated in hypertensive patients

Insulin-like growth factor-1 (IGF-1) is a single-chain peptide, which shares structural homology with pro-insulin. The majority of circulating IGF-1 originates in the liver and is regulated mainly by growth hormone (GH)(hypophysis-hepatic axis) but also by insulin and nutritional intake. GH and IGF-1 exert opposite effects on glucose metabolism. In the pathophysiology of essential hypertension there are structural changes that modify the wall-to-lumen ratio, termed vascular remodelling. Once endothelial dysfunction is established, smooth muscle cell proliferation ensues. Vascular hypertrophy associated with hypertension can also lead to the closure of small vessels and could therefore contribute to the increased vascular resistance in long-standing hypertension. Several growth factors such as FGF, TGF-b, and PDGF play an important role in this process. It is yet unknown if IGF-1 contributes in the same way. To evaluate circulating IGF-1 levels in a non selected population of hypertensive patients treated with antihypertensive drugs. To correlate them with systolic and diastolic blood pressure levels obtained by ambulatory blood pressure monitoring (ABPM). Study population: N=30 hypertensive patients, aged 38 to 77 years (60+-11), 15 males, 15 females, 14 type 2 diabetics. Anthropometric parameters: BMI (Kg/m2), waist circumference (cm). Biochemical parameters: Glycaemia, insulinaemia (uU/mL) - Immunometric assay. Immulite. DPC, insulin resistance (IR)(HOMA). HbA1c by HPLC. IGF-1 (ng/ml): 100 t kit. RIA: Nichols Institute Diagnostic. Hemodynamic parameters: 24-hour ABPM (90207spacelabs): systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP). Statistical analysis: Chi-square, linear regression. IGF-1 levels did not correlate with age, gender, type 2 diabetes mellitus, insulinaemia, IR, or HbA1c. There was an excellent correlation between IGF-1 and average DBP (r=0.4; p=0.019). The hypophysis-hepatic axis could contribute to blood pressure control. This phenomenon is not related to insulin resistance.

Myocardial Antioxidant Status in Chronic Alcoholism

Excessive ethanol intake is one of the most frequent causes of acquired dilated cardiomyopathy in developed countries. The pathogenesis is multifactorial, with the antioxidant imbalance of cardiac muscle being a potential factor. The current study evaluates myocardial antioxidant status in ethanol consumers and its relation to cardiac damage. The authors assessed superoxide dismutase, glutathione peroxidase, and glutathione reductase enzyme activities as well as the total antioxidant status capacity in myocardial samples obtained from organ donors with sudden death of traumatic or neurological origin. They studied 23 high-dose chronic alcohol consumers, 27 individuals with long-standing hypertension, and 11 healthy controls. Cardiomyopathy was defined according to standard functional and histological criteria. Patients with dilated cardiomyopathy, either of alcoholic or hypertensive origin, showed increased myocardial superoxide dismutase activities compared with patients without cardiomyopathy (p < 0.001, both) and controls (p < 0.05, both). Total antioxidant status capacity and the activity of glutathione peroxidase and glutathione reductase enzymes were similar in all groups. Superoxide dismutase activity was related to the presence of cardiac enlargement and the degree of cardiac histological damage. The amount and type of alcoholic beverages as well as the nutritional status of the patients were not related to myocardial antioxidant activity. The presence of dilated cardiomyopathy, of either alcoholic or hypertensive origin, is related to an increase in myocardial superoxide dismutase activity.

Left Heart Failure With a Normal Ejection Fraction: Identification of Different Pathophysiologic Mechanisms

Background Although heart failure with a normal ejection fraction (HFNEF) is a clinically heterogeneous syndrome, a single pathophysiologic mechanism, diastolic dysfunction, is often ascribed to explain this condition. In view of the clinical heterogeneity of these patients, we hypothesized that subgroups of HFNEF patients may have different underlying pathophysiologic mechanisms. Methods and Results Freehand 3-dimensional echocardiography was used to measure left ventricular end-systolic and end-diastolic volumes in 99 asymptomatic normal controls and 2 groups with chronic heart failure: 35 patients with normal ejection fraction with longstanding hypertension (hypertensive HFNEF) and 11 patients with hypertrophic cardiomyopathy without a history of hypertension (nonhypertensive HFNEF). These data, combined with cuff sphygmomanometry and Doppler estimates of LV end-diastolic pressure (EDP) yielded estimated pressure-volume loops and slope (E es,sb) of the end-systolic pressure-volume relationship, a load independent index of chamber contractility. Nonhypertensive HFNEF patients required high EDPs (21 ± 2 versus 15 ± 3 mm Hg in normals, P < .0001) to achieve normal EDVs (98 ± 25 versus 95 ± 21 mL in normals, P = NS). Although systolic function (E es,sb) did not differ from normal, systolic blood pressure was lower than normal in these patients (114 ± 10 versus 124 ± 14 mm Hg in normals, P < .05). Hypertensive HFNEF patients also had increased EDP (20 ± 2 mm Hg), but this was observed at higher than normal EDVs (118 ± 29 mL, P < .05). Among patients with hypertensive HFNEF, 2 subgroups emerged, 1 with a high E es,sb (4.23 ± 0.54 versus 2.1 ± 0.7 mm Hg/mL) and 1 with normal E es,sb (2.31 ± 0.51 mm Hg/mL). The former group was composed of elderly women with small body size (body surface area 1.7 ± 0.2 versus 1.9 ± 0.2 m 2, P = .02) who had concentrically remodeled ventricles and low stroke volumes. The latter group was more diverse in age, body size, and included patients of both genders with increases in ventricular volumes, stroke volume, and mass consistent with a volume overload state. Conclusion Although HFNEF is commonly thought of as being the result of a single hemodynamic mechanism, these data indicate that subgroups exist with distinctly different underlying pathophysiologies.

Use of Skin Grafting to Demonstrate Tolerance Before Kidney Transplantation Without Immunosuppression in the Recipient of a Previous Bone Marrow Transplant

Chronic renal insufficiency is a rare complication of bone marrow transplantation (BMT), occurring in 0.8% to 9.5% (1, 2) of patients and may be of sufficient severity to require renal replacement therapy. When BMT has been used as treatment for hematologic malignancy, an immune-mediated graft-versus-leukemia effect may be needed to maintain remission because systemic immunosuppression after cadaveric renal transplantation could cause risk of relapse of leukemia. The ideal kidney donor would be the same individual who donated the bone marrow. The recipient’s immune system could be identical or chimeric with that of the donor. It is difficult to be certain that 100% of the recipient immune system has been eradicated, and a small residual could proliferate to reject a donated kidney. Ethically, to submit a live donor to nephrectomy, a high level of assurance of success is needed. We present a case in which tolerance using a skin graft was demonstrated before successful kidney transplantation without immunosuppression in a BMT recipient. A 64-year-old male was referred for assessment of chronic renal insufficiency in January 2001. Four years previously, he had had chronic myeloid leukemia (CML) treated successfully with an allogenic BMT from his human leukocyte antigen (HLA)-identical (HLA-A, B, and DR only tested) sister. Two episodes of graft-versus-host-disease (GvHD) were treated with short courses of steroids and cyclosporine. In April 2001, relapse of CML was diagnosed on the basis of break-point cluster region Ableson leukemia transcripts found by polymerase chain reaction in peripheral blood and by 11 of 200 cells being of recipient (male) origin on bone-marrow examination. The relapse was successfully treated with donor lymphocyte infusion. PreBMT he had long-standing hypertension controlled by a single agent and normal kidney function. At referral, his serum creatinine had been raised for more than 24 months. An ultrasound examination revealed an absent left kidney and 9 cm right kidney. Renal insufficiency was progressive, and he was begun on peritoneal dialysis. The sister who had donated the bone marrow offered to donate a kidney. A full-thickness skin graft from the sister was performed in July 2002. One month after skin grafting, the graft had been accepted with no clinical or histologic evidence of rejection (Fig. 1). Kidney transplantation then took place without any induction or maintenance immunosuppression. Two years posttransplant, the patient remains well without episodes of transplant kidney rejection or recurrence of leukemia, with a serum creatinine of 1 mg/dL (89 μmol/L).FIGURE 1. Histology of full-thickness skin graft 1 month postgrafting showing no features of rejection.In a patient with prior documented GvHD, skin grafting provided a simple, practical, in vivo immunologic challenge to reassure us that live-donor renal allografting could be successful without immunosuppression. To our knowledge, there have been only two similar cases reported previously (3, 4). Even though the paradigm of solid-organ transplantation from the same donor in previous BMT recipients is not applicable to the vast majority of organ recipients, it offers a unique opportunity to realize the benefits of tolerance and avoid deleterious effects of immunosuppressive medication, including the risk of relapse of the primary hematologic malignancy. Rommel Ravanan Christopher R. K. Dudley Richard M. Smith Christopher J. Burton Richard Bright Renal Unit Southmead Hospital Bristol, UK Paul A. Lear Department of Surgery Southmead Hospital Bristol, UK David J. Unsworth Department of Immunology Southmead Hospital Bristol, UK

Multiple gene approaches to delineate the role of the renin-angiotensin-aldosterone system in nephropathy

Multiple gene approaches to delineate the role of the renin-angiotensin-aldosterone system in nephropathy

網膜症と腎症の進行程度に顕著な差異を認めた高齢者２型糖尿病の１例

We encountered a man who developed severe diabetic nephropathy without progression of diabetic retinopathy. He had a 14-year history of diabetes, and had been treated with sulfonylurea, and his HbA1c remained around 6.5%. He was admitted because of systemic edema and dyspnea on effort Laboratory data revealed renal failure and nephrotic syndrome, whereas there was no symptom of diabetic retinopathy. Since diabetic nephropathy usually progresses in parallel with retinopathy, it is atypical to develop severe nephropathy without retinopathy. In this case, longstanding hypertension and his genetic background including angiotensin converting enzyme D/I polymorphism might have played an important role in development of diabetic nephropathy.

Resolution of insulin treated diabetes and hypertension following resection of an asymptomatic phaeochromocytoma

The clinical and biochemical manifestations which occur in diseases associated with hormone excess, such as phaeochromocytoma, usually resolve when the hormone levels are normalised. This patient with long-standing diabetes mellitus and hypertension was incidentally found to have a completely asymptomatic phaeochromocytoma. Both hypertension and diabetes completely resolved on surgical extirpation of the tumour. We present the case of a 53-year-old male patient with diabetes and hypertension, with a blood pressure of 150/80mmHg and an HbA1c of 9% on three antihypertensive agents and insulin therapy. He was found to have a slightly raised alanine aminotransferase of 81IU/L on routine tests. An abdominal ultrasound incidentally revealed a large right adrenal mass. He had no symptoms suggestive of a phaeochromocytoma. His urinary noradrenaline excretion was raised at 4636nmol (70–580nmol/24hours). An MRI scan confirmed the right adrenal mass. He underwent an adrenalectomy and the histology confirmed a phaeochromocytoma. Subsequently, his insulin requirements fell and all therapy for diabetes and hypertension was withdrawn. While diabetes and hypertension are very common, an asymptomatic phaeochromocytoma may rarely be responsible, and its removal curative, for both conditions. Copyright © 2005 John Wiley & Sons, Ltd.

Infarcts presenting with a combination of medial medullary and posterior inferior cerebellar artery syndromes

Cerebellar and medial medullary infarctions are well-known vertebrobasilar stroke syndromes. However, their development in a patient with distal vertebral artery occlusion has not been previously reported. A 49-year-old man with longstanding hypertension suddenly developed vertigo, right-sided Horner syndrome, and left-sided weakness. An MRI of the brain showed acute infarcts in the right inferior cerebellum (posterior inferior cerebellar artery territory) and the right upper medial medulla (direct penetrating branches of vertebral artery). Magnetic resonance angiogram showed occlusion of the distal vertebral artery on the right side. Atherothrombotic occlusion of the distal vertebral artery may cause this unusual combination of vertebrobasilar stroke.

Impact of current and past blood pressure on retinal arteriolar diameter in an older population.

To examine the effects of current and past blood pressure on retinal arteriolar diameter in a general older population. Cross-sectional and longitudinal studies. Population-based cohort study of older residents from an area west of Sydney, Australia. Two thousand three hundred and thirty-five individuals (n = 2335) (aged > or = 54 years) who attended the 5-year follow-up Blue Mountains Eye Study during 1997-99. A computer-assisted method measured vessel diameters from digitized right eye retinal photographs. The narrowest quintile of central retinal arteriolar equivalent or arteriole-to-venule ratio (AVR) defined generalized arteriolar narrowing. Blood pressure was measured using a mercury sphygmomanometer. After simultaneous adjustment for age, sex, body mass index, smoking and current or past blood pressure, elevated levels of both current and past blood pressure were associated with narrower retinal arterioles [Ptrend = 0.009 and 0.007 for current and past systolic blood pressure (SBP), respectively] and lower AVR [Ptrend = 0.001 and 0.0009 for current and past diastolic blood pressure (DBP), respectively]. Generalized arteriolar narrowing was associated with both current blood pressure [adjusted odds ratio (OR) 2.4, 95% confidence interval (CI) 1.5-3.8 for the highest versus lowest quintile of current DBP] and past blood pressure (adjusted OR 1.7, 95% CI 1.1-2.6, for the highest versus lowest quintile of past DBP). Hypertension duration or control status at baseline had no additional effect on arteriolar diameter after adjusting for current blood pressure. Our data document the independent effects of both current and past blood pressure on small vessel calibre in the retina, suggesting that retinal arteriolar narrowing may result from the cumulative effects of long-standing hypertension.

Hypertension and end-organ damage in pediatric renal transplantation.

The prevalence of hypertension in pediatric patients with renal transplant (Tx) has not changed for the last three decades, remaining at 50-80%. Long-standing and uncontrolled hypertension is associated with the development of end-organ damage including allograft dysfunction, early cardiomyopathy and premature atherosclerosis. Aggressive treatment of elevated BP is an essential part of Tx care with the goal to delay graft failure and prevent the development of symptomatic cardiovascular disease in young recipients of renal Tx.

Cardiac consequences of hypertension in hemodialysis patients.

Hypertension in end-stage renal disease (ESRD) is an important risk factor for left ventricular hypertrophy (LVH), cardiac failure, coronary artery disease (CAD), and arrhythmia. LVH is generally considered an integrator of the long-term effects of hypertension and other cardiovascular (CV) risk factors and represents the strongest predictor of adverse CV outcomes in ESRD patients. The risk of heart failure is higher in patients with a history of hypertensive renal disease than in those with other diagnoses. Both coronary heart disease (CHD) and LVH predict congestive heart failure, which is often the ultimate cause of death in patients with cardiac ischemia or LVH. A history of long-standing hypertension is associated with ischemic heart disease both in cross-sectional and prospective studies in ESRD. Atrial fibrillation and ventricular arrhythmias are highly prevalent in dialysis patients and are implicated in mortality and sudden death in this population. Despite the lack of evidence from randomized controlled trials, it appears reasonable that interventions aimed at curbing the high CV mortality of ESRD should be targeted to both hypertension and LVH.

Increased glomerular albumin permeability in old spontaneously hypertensive rats.

Severe long-standing hypertension is associated with an increased urinary protein excretion. To investigate the mechanisms of this proteinuria, we measured the glomerular clearances and calculated the glomerular sieving coefficients (theta) for neutral albumin (theta(o-alb)) and for native albumin (theta(alb)) in spontaneously hypertensive rats (SHR) at the ages of 3, 9 and 14 months, in comparison with age-matched normal control Wistar rats (NCR). The hypothesis was that increases in the glomerular permeability of both negatively charged and neutral albumin would indicate a preferential size-selective dysfunction of the glomerular capillary wall (GCW), while an increased permeability to negatively charged albumin, as compared with neutral albumin, predominantly would indicate a charge-selectivity dysfunction of the GCW. A tissue (renal) uptake technique together with urinary sampling was used to assess theta. The glomerular filtration rate was assessed using the plasma to urine clearance of (51)Cr-EDTA. The theta(alb) in SHR increased 2.6 times at 14 months of age as compared with at 3 months, while there was no significant change of theta(alb) in NCR with age. Furthermore, the increased theta(alb) in old SHR correlated significantly with an increase in theta(o-alb) (r = 0.86, P<0.001), suggesting that albuminuria in old SHR primarily results from an increased number of rather unselective ('large') pores in the glomerular filter. In old age, but not at a young age, hypertensive rats develop proteinuria as a result of dysfunction of the glomerular capillary filter, affecting primarily its size-selectivity. The changes are functionally compatible with the appearance in the glomerular barrier of an increased number of more unselective pores.

Medical and surgical complications after kidney transplantation from “suboptimal donors”: one centre's experience

To overcome the organ shortage, the pool of donors can be expanded to include aged donors (>55 years old) or patients with diabetes and long-standing hypertension, the so-called “suboptimal donors.” Our experience on medical and surgical complications in kidney recipients from such donors and their impact on the graft and patient survival rates is reported. From January 1998 to April 2003, 276 kidney transplantation were performed: 107 from suboptimal donors (group A) and 169 from optimal ones (group B). After a mean follow-up of 26.8 months (range, 1–63 months), the 1-year graft survival rate was 89.3% and 97% for groups A and B, respectively. Medical complications were observed in 18.8% of group A and 6% of group B and surgical complications in 34.5% and 20%, respectively. In conclusion, even if the complication rate is higher among the suboptimal donor group, the patient and graft survival rates appear to be only slightly affected, therefore, validating the use of marginal donors.

Blunted reduction in night-time blood pressure is associated with cognitive deterioration in subjects with long-standing hypertension.

Data about the relationship of blunted reduction of night-time blood pressure (BP) with cognitive deterioration (CD) are conflicting. This study aims to explore this possible association in elderly people with long-standing hypertension. Twenty-six hypertensive subjects consecutively admitted to a rehabilitation unit over a six-month period were recruited. Exclusion criteria concerned all clinical conditions potentially related to BP variability or leading to CD. All patients underwent a clinic and 24-h BP non-invasive monitoring assessment of BP, as well as a cognitive assessment with the Mini Mental State Examination (MMSE). The presence of cerebrovascular disease (CVD) was assessed on CT films, with a standardized visual rating scale. Blunted reduction of both systolic and diastolic night-time BP were significantly associated with poorer cognitive performances (r=0.61, p=0.001 for systolic; and r=0.57, p=0.002 for diastolic, respectively). In a multiple regression model, blunted reduction of night-time BP (B=0.17, [95% confidence intervals: 1.1-1.3], p=0.008 for systolic; and B=0.15, [95% confidence intervals: 1.0-1.3], p=0.02 for diastolic) independently predicted poorer cognitive performances. In subjects with long-standing hypertension the blunted reduction of night-time BP is independently associated with lower cognitive performances.

Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the life study

Background:Peripheral endothelial dysfunction has been demonstrated in hypertension. However, its relationship to blood pressure (BP) load, vascular structure, and metabolic disturbances in patients with long-standing, previously treated hypertension is unclear.Methods:A total of 41 patients with stage I to III essential hypertension and electrocardiographic left ventricular hypertrophy were studied. After 2 to 3 weeks of placebo treatment we measured nitroprusside-induced relaxation (NIR), acetylcholine-induced relaxation (AIR), and media:lumen ratio in isolated, subcutaneous resistance arteries by myography, as well as 24-h ambulatory BP, and serum lipids.Results:Maximal AIR correlated negatively with median 24-h diastolic BP (r = −0.42, P = .01), and sensitivity to AIR correlated negatively with serum low density lipoprotein (LDL) (r = −0.36, P < .05). In multiple regression analyses, sensitivity to AIR correlated negatively with serum LDL (β = −0.33) independently of maximal NIR (β = 0.41) (adjusted R2 = 0.26, P < .01). Maximal acetylcholine-induced relaxation correlated negatively with median 24-h diastolic BP (β = −0.38) independently of maximal NIR (β = 0.45) (adjusted R2 = 0.32, P < .001). Acetylcholine-induced relaxation was not significantly related to diabetes or to media:lumen ratio (r = −0.26, NS).Conclusions:High diastolic BP and high serum LDL were associated with impaired maximal AIR and reduced sensitivity to AIR, respectively, independently of smooth muscle cell responsiveness to nitroprusside. This indicated decreasing endothelial function in small resistance arteries with increasing BP and increasing LDL in hypertension. Endothelial function was not significantly related to vascular structure of the resistance arteries or to diabetes in these patients with long-standing hypertension.

Refractory hypotension and edema caused by right atrial compression in a woman with polycystic kidney disease

We present the case of a 60-year-old woman with a history of autosomal dominant polycystic kidney disease and long-standing hypertension who developed persistent hypotension. While in the hospital for the treatment of bacteriemia, the patient had low systolic blood pressures (90 to 100 mm Hg), which was thought to be the consequence of infection. After the infection was adequately controlled and the blood pressure did not improve, an echocardiogram was done to further elucidate her hypotension. It was nondiagnostic and revealed an ejection fraction of 70% with left ventricular hypertrophy. Shortly after discharge, she developed significant lower extremity edema and her blood pressure remained low. Due to the low blood pressure it was not possible to mobilize the fluid with her dialysis treatments. A repeat transthoracic echocardiogram at that time revealed that the right atrium was partially compressed throughout the cardiac cycle by polycystic hepatic tissue. This tissue invaginated up through the right hemidiaphragm. A partial liver resection was considered for the patient. Instead, right nephrectomy was performed and the blood pressure improved.

From hypertension to heart failure: update on the management of systolic and diastolic dysfunction

The aging of the population of the United States (US) will bring with it higher numbers of patients with coronary heart disease and heart failure (HF). Because HF already imposes severe economic and medical burdens on our health care system, it is imperative to optimize primary and secondary prevention of cardiovascular (CV) disease. In most cases, HF develops as a result of either long-standing hypertension or a myocardial infarction (MI). Other than cardiac death, HF represents the last stage in the progression of CV disease, which begins with CV risk factors such as hypertension, dyslipidemia, obesity, and smoking. These risk factors lead to the development of left ventricular (LV) hypertrophy or an MI (or both), which lead to LV dysfunction and, finally, to HF. The prognosis of HF is poor, the 5-year survival rate being approximately 25%. Heart failure may be due to either LV systolic or diastolic dysfunction, the latter having a normal ejection fraction. Because CV disease is progressive, interventions are possible at all stages along the CV continuum. β-Blockers (βB) are recommended agents at several stages of CV disease. Large-scale trials have shown that βB significantly reduce risks for morbidity and mortality in patients with HF. Ongoing studies should help to clarify further the optimal cardioprotective therapies in patients with HF.

Vascular Factors in Alzheimer's Disease

Vascular involvement in Alzheimer disease (AD) is not necessarily coincident. Current evidence suggests the neuropathology of Alzheimer type of dementia comprises more than amyloid plaques and neurofibrillary tangles. At least a third of recognized AD cases may exhibit cerebrovascular pathology, which also constitutes distinct small vessel disease. Cerebral amyloid angiopathy, microvascular degeneration affecting the cerebral endothelium and smooth muscle cells, basal lamina alterations, hyalinosis, and fibrosis are frequently evident in AD. These changes may be accompanied by perivascular denervation that is causal in the cognitive decline of AD. In addition, amyloid beta protein appears directly involved in the degeneration of both the larger perforating arterial vessels as well as cerebral capillaries, which represent the blood-brain barrier. The cerebrovascular pathology in AD also encompasses macro- and micro-infarctions, hemorrhages, lacunas, and ischemic white-matter changes. An interaction of both perivascular mediators and derived factors would perturb the brain vasculature. Peripheral vascular factors such as long-standing hypertension, atrial fibrillation, coronary or carotid artery disease, and diabetes mellitus are also apparent in AD. These factors would modify the cerebral circulation such that a sustained hypoperfusion or oligemia is impacted upon the aging processes to induce the characteristic pathology.

Predictors of renal and patient outcomes in atheroembolic renal disease: a prospective study.

Atheroembolic renal disease (AERD) is part of a multisystemic disease accompanied by high cardiovascular comorbidity and mortality. Interrelationships between traditional risk factors for atherosclerosis, vascular comorbidities, precipitating factors, and markers of clinical severity of the disease in determining outcome remain poorly understood. Patients with AERD presenting to a single center between 1996 and 2002 were followed-up with prospective collection of clinical and biochemical data. The major outcomes included end-stage renal disease (ESRD) and death. Ninety-five patients were identified (81 male). AERD was iatrogenic in 87%. Mean age was 71.4 yr. Twenty-three patients (24%) developed ESRD; 36 patients (37.9%) died. Cox regression analysis showed that significant independent predictors of ESRD were long-standing hypertension (hazard ratio [HR] = 1.1; P < 0.001) and preexisting chronic renal impairment (HR = 2.12; P = 0.02); use of statins was independently associated with decreased risk of ESRD (HR = 0.02; P = 0.003). Age (HR = 1.09; P = 0.009), diabetes (HR = 2.55; P = 0.034), and ESRD (HR = 2.21; P = 0.029) were independent risk factors for patient mortality; male gender was independently associated with decreased risk of death (HR = 0.27; P = 0.007). Cardiovascular comorbidities, precipitating factors, and clinical severity of AERD had no prognostic impact on renal and patient survival. It is concluded that AERD has a strong clinical impact on patient and renal survival. The study clearly shows the importance of preexisting chronic renal impairment in determining both renal and patient outcome, this latter being mediated by the development of ESRD. The protective effect of statins on the development of ESRD should be evaluated in a prospective study.