Influence of arterial elasticity and vessel dilatation on arteriovenous fistula maturation: a prospective cohort study.

BACKGROUND: Arteriovenous fistula maturation requires dilatation of the anastomosed artery and vein. The factors that affect dilatation and the mechanisms by which dilatation promotes maturation are not understood. This pilot study tested two hypotheses: that low arterial elasticity is associated with maturation failure, and that vessel dilatation is required for adequate fistula blood flow during dialysis. METHODS: Thirty-two patients underwent preoperative measurement of small artery elasticity index, and pre-anastomosis measurement of artery and vein luminal diameters during fistula surgery. Fistulas were considered mature if they were used successfully in three consecutive treatments within 6 months. A mathematical model was used to determine whether vessel dilatation is needed for adequate fistula flow. RESULTS: Six fistulas were excluded from analysis of maturation because dialysis did not begin within 6 months. Twenty-one of the remaining 26 fistulas were located in the upper arm. Six of 26 failed to mature, and all 6 developed stenosis. The average small artery elasticity index was lower in failed than in matured fistulas (2.25 versus 3.71 ml/ mmHg x 100, P = 0.02). Artery and vein diameters of the 32 patients ranged from 2.5 to 5.0 and 3.5 to 7.0 mm, respectively. When the diameters were applied to the mathematical model, predicted fistula flows ranged from 412 to 1380 ml/min. CONCLUSIONS: Low arterial elasticity is associated with stenosis and fistula maturation failure. However, vessel dilatation is not needed for adequate blood flow except at the smaller diameters in this study. We speculate that low elasticity promotes development of stenosis. Larger studies are needed to confirm these promising results and to determine whether therapies directed at improving elasticity can improve maturation.

Diagnosis of pheochromocytoma in the setting of Parkinson disease.

BACKGROUND: A 59-year-old man with a 7-year history of Parkinson disease (PD) presented with episodes of sudden, severe headaches with neck pain, tachycardia, sweating and pallor. During these episodes, the patient showed marked elevations in blood pressure, regardless of posture. This was unusual, given that he had no prior history of hypertension. The array of symptoms raised suspicions of pheochromocytoma, but diagnosis was challenging, as the standard diagnostic biochemical tests were confounded by dopaminergic medications. Further work-up revealed left adrenal medullary hyperplasia. Several reports exist of pseudopheochromocytoma in patients on dopaminergic therapy, but this is the first documented case of pheochromocytoma syndrome due to adrenal medullary hyperplasia in a patient with PD. This case highlights the challenges of performing a diagnostic work-up in a PD patient with symptoms suggestive of pheochromocytoma, and illustrates the utility of (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission CT in making a diagnosis.Investigations. Physical examination, laboratory tests, abdominal MRI scan, abdominal (123)I-MIBG scan, abdominal (18)F-fluorodeoxyglucose PET scan. DIAGNOSIS: Pheochromocytoma syndrome due to adrenal medullary hyperplasia.Management. Surgical excision of the left adrenal gland.

Management of hypertension in patients with cardiac disease: use of renin-angiotensin blocking agents.

Inhibition of renin-angiotensin system (RAS) activity using angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ARBs) is beneficial in patient populations with left ventricular dysfunction or systolic heart failure (HF) and other forms of heart disease. In high-risk patients with coronary heart disease (CHD), treatment with these agents reduces the mortality rate and improves secondary outcomes. Individuals with stable CHD who are at lower risk benefit less from treatment. RAS inhibition also provides some clinical benefit to patients with diastolic HF and preserved left ventricular function. Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular events and all-cause mortality in patients with hypertension. Treatment with an ARB reduces the risk for adverse cardiovascular outcomes in patients with hypertension and LVH. The benefits correlate with regression of LVH, and the effect is independent of the degree of blood pressure lowering. Finally, studies indicate that a history of hypertension in patients who have not had a myocardial infarction (MI) increases the risk for HF after MI; the risk is decreased in patients with hypertension who receive treatment with a RAS inhibitor.

Assessment of the validation of blood pressure monitors: a statistical reappraisal.

Protocols to determine the accuracy of noninvasive blood pressure monitors have been published by the Association for the Advancement of Medical Instrumentation, the British Hypertension Society, and the European Society of Hypertension (ESH). We compared the statistical basis for each of these protocols. Although the Association for the Advancement of Medical Instrumentation and British Hypertension Society protocols require a minimum of 85 participants, the ESH protocol requires only 33 participants. The reduced sample size results in a reduction in statistical power from 98 to 70%, which brings into question the applicability of the ESH (International) protocol.

Racial analysis of patients with myocardial infarction complicated by heart failure and/or left ventricular dysfunction treated with valsartan, captopril, or both.

OBJECTIVES: African Americans have a high incidence of heart failure (HF). Limited retrospective observational subgroup analyses of patients with left ventricular systolic dysfunction (LVSD) suggest marginal benefit of angiotensin-converting enzyme inhibitors in the prevention of HF hospitalizations or total mortality in African Americans. BACKGROUND: Very few data exist concerning the effectiveness of angiotensin receptor blockers in this population. METHODS: Baseline characteristics, treatments, and outcomes of patients from the U.S. (3,390 white and 340 African-American patients) in the VALIANT (VALsartan In Acute myocardial iNfarcTion) trial were compared. This trial included patients with an acute myocardial infarction (MI) after initial stabilization and documented LVSD and/or HF. Patients were randomly assigned to receive treatment with valsartan, captopril, or the combination; follow-up continued for up to 3 years (median 24.7 months). RESULTS: African Americans had more coronary risk factors, more markers of poor outcome after MI, and were less likely to be revascularized when compared with white patients. After adjusting for treatment assignment, baseline characteristics, and post-infarction parameters, no difference was found in the 3-year rate of all-cause mortality, cardiovascular mortality, rehospitalization for HF, recurrent MI, or stroke between the 2 groups. CONCLUSIONS: African Americans sustaining an acute MI with LVSD and/or HF had similar clinical outcomes compared with white Americans. Valsartan, captopril, or the combination had comparable effects on cardiovascular morbidity and mortality in African Americans and white Americans.

Nebivolol: pharmacologic profile of an ultraselective, vasodilatory beta1-blocker.

Beta-blockers are well-established therapeutic agents in the treatment of hypertension and cardiovascular disease. However, these agents are highly heterogeneous. Beta-blockers differ in their ancillary pharmacologic properties, which are clinically important. Nebivolol is a highly selective beta(1)-adrenergic receptor blocker that induces vasodilation through stimulation of the endothelial nitric oxide/L-arginine pathway. As a racemic mixture of d- and l-enantiomers, nebivolol is highly lipophilic and rapidly absorbed. Nebivolol undergoes extensive hepatic metabolism through the cytochrome P450 2D6 (CYP2D6) system. As a result of genetic polymorphisms, CYP2D6 has variable activity, manifested by extensive and poor metabolizers of nebivolol. Time to maximum concentration is 0.5 to 2 hours, and half-life is 11 hours in extensive metabolizers; these values are about 3 times longer in poor metabolizers. Urinary and fecal excretion of unchanged nebivolol is less than 0.5% of the dose. Nebivolol has a unique hemodynamic profile of reduced systemic vascular resistance and increased left ventricular function. These properties are attributed to its vasodilating action and contrast with the hemodynamic effects of conventional beta-blockers. Nebivolol is thus a novel beta-blocker with several important pharmacologic properties that distinguish it from traditional beta-blockers. These unique properties may confer clinical benefits beyond simple blood pressure lowering.

Now or never: optimal antihypertensive therapy in the elderly.

Hypertension control rates in the elderly, particularly for systolic hypertension, are poor and lower than control rates in other age groups. Older patients often require treatment with specific antihypertensive drugs because of concomitant conditions and usually need > or =2 drugs to control blood pressure. Combining drugs with complementary mechanisms of action may improve both blood pressure control and the tolerability of individual drugs. A number of fixed-dose combinations have shown efficacy in older patients and in stage 2 hypertension, including various combinations involving diuretics and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

Fibromuscular dysplasia: an uncommon cause of secondary hypertension.

Fibromuscular dysplasia is a noninflammatory vascular disease that commonly affects the distal two thirds of the renal artery and branch vessels, but occasionally involves other arteries. Progression of stenosis occurs in 16%-38% of renal arteries. Although the etiology is unknown, genetic studies suggest a relationship to the angiotensin-converting enzyme I allele. Thin, young Caucasian women without a family history of hypertension are most commonly affected. An abdominal or flank systolic-diastolic bruit is an important clue for the diagnosis. Most noninvasive screening tests are not sensitive or reproducible to be used to rule out renal artery stenosis, but digital subtraction renal angiography usually confirms the diagnosis. Percutaneous renal artery angioplasty is the treatment of choice, but may not result in normalization of blood pressure if diagnosis is delayed. Since restenosis occurs, continued follow-up is necessary.

Arterial elasticity and erectile dysfunction in hypertensive men.

Erectile dysfunction is a common symptom among hypertensive patients that impairs quality of life and adherence to antihypertensive pharmacologic therapy. It is also associated with cardiovascular risk factors and disease. The Sexual Health Inventory in Men (SHIM) was administered to 105 ambulatory hypertensive patients, and large and small artery elasticity indices were measured. Each variable was examined in a simple linear regression model or 1-way analysis of variance model to determine each variable's relationship with the SHIM score. Variables that were significantly associated with the SHIM score in the univariate models included age, duration of hypertension, peripheral vascular disease, and small artery elasticity. Large artery elasticity was not significantly associated with the SHIM score. In the multivariate model, age, hypertension duration, and peripheral vascular disease were associated with a lower SHIM score. This study demonstrates a relationship between erectile dysfunction and reduced artery elasticity.

Obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome is caused by upper airway collapse during inspiration, causing intermittent hypoxemia, hypercapnia, acidosis, sympathetic nervous system activation, and arousal from sleep. Nighttime blood pressure is higher, but unexpectedly, daytime hypertension occurs. The prevalence of hypertension is very high and the incidence of hypertension increases as the number of apneic and hypopneic events per hour rises. Obesity is a major predisposing factor for the development of obstructive sleep apnea. Daytime sleepiness, snoring, and breathing pauses are important symptoms to elicit from the patient or sleep partner. Resistant hypertension is an important clue. Overnight polysomnography is required for diagnosis. Weight loss, avoidance of nocturnal sedatives, cessation of evening alcohol ingestion, and avoidance of the supine position during sleep are initial therapeutic actions in mild obstructive sleep apnea syndrome. Continuous positive airway pressure is the treatment of choice for patients unable to find relief from lifestyle changes. Blood pressure modestly improves with treatment.

Phosphodiesterase-5 inhibitors and their hemodynamic effects.

Erectile dysfunction occurs commonly in untreated and treated hypertensive patients, impairing adherence to treatment and quality of life. Furthermore, it is a marker for enhanced risk for cardiovascular disease. Phosphodiesterase type 5 (PDE5) inhibitors, sildenafil, vardenafil, and tadalafil, provide effective treatment of erectile dysfunction. They reduce blood pressure in healthy patients: sildenafil 100 mg, -3.7/-3.6 mm Hg; vardenafil 20 mg, -7.5/-8 mm Hg; and tadalafil 20 mg, -1.6/-0.8 mm Hg. Greater declines in blood pressure with a PDE5 inhibitor may be observed in treated and untreated hypertensive patients. The additive effect of PDE5 inhibitors with one or multiple antihypertensive drugs is modest. alpha(1)-Blockers, except tamsulosin, may result in larger declines in blood pressure and cause orthostatic hypotension. Thus, caution should be exercised by using the lowest doses of proportional, variant(1)-blockers and PDE5 inhibitors in combination. Nitrates in combination with PDE5 inhibitors cause a profound decline in blood pressure and are contraindicated.

Elevated endothelin-1 levels are associated with decreased arterial elasticity in hypertensive patients.

Endothelin-1 stimulates collagen synthesis and is increased in hypertension, but its effect on collagen degradation remains unknown. The current study tested the hypothesis that elevated endothelin-1 levels are associated with decreased collagenase activity, markers of collagen degradation, and arterial compliance in hypertensive patients. Normotensive (n = 10) and hypertensive (n = 13) patients who were not on any antihypertensive medication were recruited, and small and large artery elasticity index, systemic vascular resistance, pulse pressure, and blood pressure were determined using blood pressure waveform analysis. Large artery elasticity index and collagen degradation products were decreased whereas endothelin-1, systemic vascular resistance, and pulse pressure were elevated in hypertensive patients. Plasma endothelin-1 was negatively correlated with a cross-linked C-terminal telopeptide of collagen type I, a collagen degradation marker (r = -0.43; p = 0.04), collagenase matrix metalloproteinase-1 (r = -0.48; p = 0.02), and large artery elasticity (r = -0.45; p = 0.03) and positively correlated with pulse pressure (r = 0.68; p = 0.0005). These results suggest that endothelin-1 contributes to decreased arterial compliance in hypertension via inhibition of collagen degradation.

Hyperthyroidism: a secondary cause of isolated systolic hypertension.

Isolated systolic hypertension is the most common form of hypertension, especially among patients 50 years or older. What is not appreciated is that there are secondary causes of isolated systolic hypertension. Hyperthyroidism increases systolic blood pressure by decreasing systemic vascular resistance, increasing heart rate, and raising cardiac output. Potential cardiovascular consequences of hyperthyroidism include atrial arrhythmias (especially atrial fibrillation), pulmonary hypertension, left ventricular hypertrophy, and heart failure. The prevalence of hypertension is greater among hyperthyroid patients than euthyroid patients. Whether there is a blunted nocturnal decline in ambulatory blood pressure among hyperthyroid patients is more controversial. Treatment is associated with a reduction in systolic blood pressure, heart rate, and cardiac output.

Relationship between glycosylated hemoglobin and arterial elasticity.

Arterial elasticity is decreased in diabetes, but it is unclear whether there is a relationship between glycosylated hemoglobin (HbA1c) and arterial elasticity. To evaluate this question, 111 subjects with diabetes mellitus had HbA1c and arterial elasticity determined in an academic outpatient setting. Three measurements of arterial elasticity indices were obtained supine using the HDI/PulseWave CR-2000 Research CardioVascular Profiling System (Hypertension Diagnostics Inc., Eagan, MN). The study population was 49% black and 51% women. Population characteristics included age, 49.2 years; duration of diabetes, 12.1 years; HbA1c, 8.9%; large artery elasticity, 11.8 mL/mm Hg x 10; and small artery elasticity, 4.7 mL/mm Hg x 100. Age correlated with diminished large artery elasticity. Women had a lower large artery elasticity than men (10.6 vs. 13.3 mL/mm Hg x 10; p = 0.0002). Decreasing small artery elasticity was associated with increasing age (p = 0.0001), HbA1c (p = 0.0184), and African-American ethnicity (p = 0.0306). Women had less small artery elasticity than men (3.8 vs. 5.8 mL/mm Hg x 100; p = 0.0001). Black diabetic patients had a reduced arterial elasticity compared with whites. Increasing HbA1c is associated with decreasing small artery elasticity, but not large artery elasticity. In diabetic patients, small artery elasticity is reduced to a greater extent in women than men and in blacks than whites.

Antihypertensive pharmacobezoar.

Most antihypertensive drugs have known side effects that are elicited by the careful clinician taking care of hypertensive patients. However, many antihypertensive medications utilize drug delivery systems that prolong the duration of blood pressure reduction. The gastrointestinal therapeutic system that is used with nifedipine, isradipine, and verapamil has a unique side effect. Obstruction may occur at the site of a previous surgical repair (pyloric stenosis or gastroplasty) or stenosis of the esophagus, small intestine, or colon. The same delivery system is used with methylphenidate, oxybutynin, glipizide, and doxazosin. Although this complication is rare, physicians who prescribe and care for hypertensive patients should recognize this potential problem.

Ophthalmoscopic findings in malignant hypertension.

Malignant hypertension may present with retinopathy, choroidopathy, and optic neuropathy. Flame-shaped retinal hemorrhages, an early finding, are due to smooth muscle necrosis and bleeding along the nerve fiber layer. Cotton-wool spots, or cytoid bodies, are not exudates, but rather are retinal infarcts. Hypertensive optic neuropathy is a late finding. Optical coherence tomography is a relatively new imaging technique for evaluating retinal thickness and the location of pathology in patients with malignant hypertension.

Assessment of test repeatability of arterial stiffness index.

BACKGROUND: Increased arterial stiffness is an early indicator of vascular disease. Several methods may be used to determine arterial stiffness. One method obtains an arterial stiffness index from the vascular dynamics of oscillometric-derived brachial artery pressure. METHODS: To determine the test-retest repeatability of the CardioVision MS-2000, 47 healthy hospital employees had five consecutive measurements of arterial stiffness index measured after a 5-10 min period of rest and then repeated after an average of 146.8 days. Their mean age was 37 years and 71% were women. RESULTS: The mean arterial stiffness index was 39.6+/-9.7 and 37.2+/-10.5 mmHg x10 (P=0.22) for the first and second time period, respectively. We computed an intraclass correlation coefficient of 0.31 and 0.33 for the first and second time periods, which is the measure of consistency or agreement of arterial stiffness index values within cases. The intraclass correlation coefficient for systolic blood pressure, diastolic blood pressure, heart rate and arterial stiffness index were 0.68 (P=0.0001), 0.70 (P=0.0001), 0.35 (P=0.02) and 0.25 (P=0.08), respectively. CONCLUSION: The results of this study suggest poor test-retest repeatability if consecutive measurements are used. The intraclass correlation coefficient, however, could be improved by eliminating the highest and lowest value from a set of measurements.

Polycystic kidney disease.

Polycystic kidney disease, an inherited systemic disorder, is characterized by the development of multiple cysts in the kidneys and other organs. Patients can present at any age, but more often come to clinical attention (unless there is a family history) after age 30. Patients who are diagnosed before age 30 have a worse renal survival. Although palpation of the abdomen occasionally provides a clue to the presence of polycystic kidney disease, radiographic procedures most often suggest the diagnosis. Mutations in the PKD1 or PKD2 genes give rise to cyst formation. Flank pain, hematuria, polyuria, nephrolithiasis, urinary tract infections, and hypertension may be part of the syndrome of polycystic kidney disease. It is the fourth most common cause of end-stage renal disease. Blood pressure treatment goals are less than 130/80 mm Hg. Treatment should include the use of angiotensin-converting enzyme inhibitors.

Aortic dissection.

Aortic root enlargement is generally asymptomatic, with few clinical clues, but may be observed as an incidental finding on a chest x-ray, echocardiogram, or contrast-enhanced computerized tomogram of the chest. Aortic dissection is one of the most feared complications of hypertension. A history of hypertension is commonly present, but the systolic blood pressure in type A dissection (proximal to the left subclavian artery) has been found to be less than 150 mm Hg in 64% of patients. However, 71% of type B dissections (distal to the left subclavian artery) present with a systolic blood pressure 150 mm Hg or higher (International Registry of Acute Aortic Dissection). Most frequently, onset of symptoms is in the daytime, especially between 6 a.m. and noon. Severe sharp chest pain that is abrupt in onset is the most likely presentation. Migrating pain is uncommon. Although a pulse deficit with decreased or absent carotid, brachial, or femoral pulses occurs in only 30% of patients, three or more deficits predict an in-house mortality of about 60%. A chest x-ray finding of a widened mediastinum is present in 62.6% of type A and 56% of type B dissections. Contrast-enhanced computerized tomography or transesophageal echocardiography is the most commonly performed procedure for diagnosis. In-house mortality has been found to be 32.5% in type A dissections and 13% in type B dissections.