Long-standing Hypertension Research Articles

Pathology and pathogenesis of idiopathic portal hypertension with an emphasis on the liver.

Idiopathic portal hypertension (IPH) is characterized by a long-standing presinusoidal portal hypertension of unknown etiology in adults. Some unidentified agent(s) affect(s) the intrahepatic small portal veins or portal tracts. Immunological disturbance, thromboembolism, infectious etiology and/or increased fibrogenesis in portal tracts are suspected as being candidates for the primary agent(s). During the long clinical course of IPH, several pathological changes may occur, including subcapsular parenchymal atrophy, atrophy of the liver, portal and parenchymal fibrosis, and portal venous phlebosclerosis and thrombosis. The last-named of these lesions is mostly found in patients with a history of splenectomy. Subcapsular parenchymal and hepatic atrophy may result from a hepatocellular dropout via apoptosis or necrosis because of intrahepatic hemodynamic disturbances, particularly chronic portal venous blood insufficiency. Pericellular fibrosis and thin fibrous septa are also frequently found and associated with activated perisinusoidal cells positive for smooth muscle actin. At the same time, vague nodular hyperplasia of hepatocytes not surrounded by fibrous septa is not infrequently seen. It may resemble nodular regenerative hyperplasia, partial nodular transformation, or focal nodular hyperplasia. However, liver cirrhosis does not occur even at the terminal stage. Taking these findings into consideration, a new staging of IPH with a combination of hepatic parenchymal atrophy and portal venous thrombosis was proposed: non-atrophic liver without subcapsular parenchymal atrophy (stage I), non-atrophic liver with subcapsular parenchymal atrophy (stage II), atrophic liver with subcapsular parenchymal atrophy (stage III), and portal venous occlusive thrombosis (stage IV). IPH livers are likely to progress from stage I to stage III. Stage IV, which occurs relatively late, has a poor prognosis. This staging is applicable to clinical and autopsy cases without any histological data.

White Matter Damage is Associated with Matrix Metalloproteinases in Binswanger’s Disease

81 BACKGROUND: Binswanger’s disease (BD) is a progressive form of vascular dementia (VaD) of the elderly associated pathologically with demyelination and clinically with disturbances of gait and intellect. It is commonly found in patients with fibrinoid and hyaline changes in brain arterioles secondary to long-standing hypertension. Because of the remodeling seen in the blood vessel wall, and the role of the matrix metalloproteinases (MMPs) in extracellular matrix injury and repair, we hypothesized that disturbances in the MMPs may be involved in the BD type of VaD. METHODS: To test the hypothesis, brain tissues from five patients with VaD of the BD or multi-infarct type were immunostained with antibodies to glial fibrillary acidic protein (GFAP), a macrophage/microglial cell marker (PG-M1), gelatinase A (MMP-2), stromelysin-1 (MMP-3), and gelatinase B (MMP-9). Control tissues were from eight elderly patients: four with strokes without dementia, and four without neurological diseases. RESULTS: Macrophage/microglia (PG-M1)-positive cells appeared around infarcts both in cases with strokes without dementia, and in those with VaD. In two of the three BD patients PG-M1 cells were prominent near damaged arterioles and scattered diffusely in white matter. MMP-2 was seen normally in perivascular macrophages and astrocytic processes near blood vessels, and was present in patients with strokes in reactive astrocytes, particularly those with a gemistocytic shape. MMP-9 was seen only in acute lesions. MMP-3 was seen in PG-M1 staining microglia/macrophage cells around the acute infarctions. In BD MMP-3 persisted in tissue macrophages, disappearing in long-standing white matter gliosis. CONCLUSIONS: These observations suggest that MMPs participate in the demyelination associated with injured blood vessels in the BD form of VaD. Chronic inflammation, which may be amenable to treatment, may be a factor in the progressive forms of VaD.

White Matter Damage is Associated with Matrix Metalloproteinases in Binswanger’s Disease

81 BACKGROUND: Binswanger’s disease (BD) is a progressive form of vascular dementia (VaD) of the elderly associated pathologically with demyelination and clinically with disturbances of gait and intellect. It is commonly found in patients with fibrinoid and hyaline changes in brain arterioles secondary to long-standing hypertension. Because of the remodeling seen in the blood vessel wall, and the role of the matrix metalloproteinases (MMPs) in extracellular matrix injury and repair, we hypothesized that disturbances in the MMPs may be involved in the BD type of VaD. METHODS: To test the hypothesis, brain tissues from five patients with VaD of the BD or multi-infarct type were immunostained with antibodies to glial fibrillary acidic protein (GFAP), a macrophage/microglial cell marker (PG-M1), gelatinase A (MMP-2), stromelysin-1 (MMP-3), and gelatinase B (MMP-9). Control tissues were from eight elderly patients: four with strokes without dementia, and four without neurological diseases. RESULTS: Macrophage/microglia (PG-M1)-positive cells appeared around infarcts both in cases with strokes without dementia, and in those with VaD. In two of the three BD patients PG-M1 cells were prominent near damaged arterioles and scattered diffusely in white matter. MMP-2 was seen normally in perivascular macrophages and astrocytic processes near blood vessels, and was present in patients with strokes in reactive astrocytes, particularly those with a gemistocytic shape. MMP-9 was seen only in acute lesions. MMP-3 was seen in PG-M1 staining microglia/macrophage cells around the acute infarctions. In BD MMP-3 persisted in tissue macrophages, disappearing in long-standing white matter gliosis. CONCLUSIONS: These observations suggest that MMPs participate in the demyelination associated with injured blood vessels in the BD form of VaD. Chronic inflammation, which may be amenable to treatment, may be a factor in the progressive forms of VaD.

Portal venous calcifications 20 years after portosystemic shunting: Demonstration by spiral CT with CT angiography and 3D reconstructions

Background: Evaluation of the value of spiral computed tomography (SCT), and postprocessing procedures in patients with extensive portal venous calcifications 20 years after portosystemic shunting was performed. Methods: In two patients spiral CT (SCT) examinations of the abdomen (slice thickness 3 mm, table feed 6 mm/s) were performed prior and after application of 150 ml of contrast material administered at a flow rate of 4 ml/s. Axial images were reconstructed at 2 mm increments for postprocessing procedures and 6 mm increments for axial source images. Postprocessing was performed with a maximum intensity projection (MIP) and shaded surface display (SSD) imaging program. Results: In both cases preoperative plain film radiography of the chest and abdomen showed large curvilinear calcifications located at the upper quadrant of the abdomen. The calcifications were directed along the expected axis and position of the portal vein and the portosystemic venous anastomosis. Axial CT slices and CTA showed that the calcifications were located in the vessel wall and that the portal vein lumen as well as the portosystemic venous anastomosis were patent. Conclusion: Long-standing portal hypertension is capable of causing portal venous calcifications due to mechanical stress to the vessel wall even years after performing portosystemic shunting. Typically, the calcifications are directed along the expected axis and position of the portal vein. SCT of the portal venous system is a reliable method to differentiate between calcifications in a thrombus or in the vessel wall, which may have therapeutic significance.

The eyes see only what the mind knows

A 50-year-old male presented who complained of retrosternal and epigastric pain described as 8/10 in severity and 3–4 h in duration. The patient had multiple coronary risk factors, including history of longstanding diabetes, hypertension, and family history of premature coronary artery disease. He was on maintenance hemodialysis for chronic renal insufficiency. Figure 1 shows the electrocardiogram (EKG).

Mucous membrane pemphigoid, thymoma, and myasthenia gravis

In November 1997, approximately 1 year before being evaluated at the Mayo Clinic, Rochester, a 63-year-old woman presented with erosive tongue lesions that were diagnosed by her physician as oral lichen planus. The lesions responded well to 3 months of treatment with systemic and topical corticosteroids and topical antiyeast medication. She stopped taking the medications and had a relapse. A few months after the oral lesions developed, her left eyelid became ptotic. Results of magnetic resonance imaging of her brain were normal, and the ptosis resolved spontaneously after 2 weeks. One year later, her right eyelid began to droop, and the results of edrophonium testing were positive. She was prescribed prednisone, 30 mg daily, and pyridostigmine, as needed. The ptosis improved, but never fully resolved. Radiography revealed a left ‘‘thyroid nodule,’' but computed tomography did not show a mediastinal mass. She was advised to have the ‘‘nodule’' removed surgically and came to the Mayo Clinic, Rochester, for a second opinion. Her medical history was significant for the following: tinnitus, glaucoma, early bilateral cataracts, and long-standing hypertension, for which she took losartan, 50 mg twice daily. Other medications included: prednisone, 30 mg daily; pyridostigmine as needed; famotidine, 40 mg daily; and eyedrops for glaucoma. She denied any history of hyperthyroidism or hypothyroidism, head and neck irradiation, family history of thyroid disease, or diplopia. Hepatitis serologic studies revealed hepatitis B exposure and recovery, hepatitis C immunity, and a previous hepatitis A viral infection. On examination at the Mayo Clinic, Rochester, an erosive hypertrophic plaque was noted on the posterior dorsal half of the tongue, and vesicles and erythematous erosions on the hard and soft palates ( Fig. 1a). A lace-like white pattern was seen on the buccal mucosa bilaterally, and a small erosive patch on the left buccal mucosa ( Fig. 1b). Ocular and nasal mucous membranes were normal in appearance, and there were no pertinent skin findings. Dermatopathologic examination of an excisional biopsy specimen from the left dorsum of the tongue demonstrated an ulcer with epitheliomatous hyperplasia and a granulomatous reaction, presumably due to yeast infection. Silver staining showed hyphae and yeast at the base of the tongue ulcer. The results of the direct immunofluorescence study were negative and revealed no lichenoid changes on hematoxylin and eosin staining. Indirect immunofluorescence testing of the serum revealed a 1 : 80 titer of basement membrane zone antibodies, reflecting pemphigoid. This test was positive on repeat study. Salt-split skin on monkey esophagus revealed an epidermal pattern of basement membrane zone antibodies. Treatment included fluocinonide gel applied to the involved areas four times daily and oral antiyeast therapy (fluconazole, 200 mg once daily by mouth) while the rest of the evaluation was being completed. Figure 1(a)Open in figure viewerPowerPoint Erosive hypertrophic tongue plaque. Figure (b) Open in figure viewerPowerPoint Erosive patch on the buccal mucosa. As part of the evaluation of the ptosis, a myasthenia gravis antibody panel was performed. It revealed the following abnormalities: striated muscle antibody at 1 : 480 (reference range, <1 : 60), acetylcholine receptor binding antibody at 6.33 nmol/L (reference range, ≤ 0.02 nmol/L), acetylcholine receptor blocking antibody at 31% (reference range, 0–25%), and acetylcholine receptor modulating antibody at 100% (reference range, 0–20%), suggesting thymoma. Treatment included pyridostigmine, 30–45 mg 3–4 times daily, to control the myasthenia symptoms, while the ill-defined neck mass was being evaluated. A mildly enlarged thyroid was noted on physical examination. Hematology panel revealed thyroid-stimulating hormone (TSH) levels in the low normal range; the thyroid microsomal antibody was normal. Chest radiography showed minor tracheal deviation, and a previous computed tomogram showed what appeared to be a 3-cm enlarged mass in the thyroid. Ultrasonographically guided thyroid biopsy did not show malignancy, but a benign mesenchymal-type tumor was found and surgical excision was planned. Intraoperatively, a thymoma of the left cervical thymic tongue was found. At 6 months' follow-up, the ptosis and oral mucosal lesions had improved significantly, although she continued topical corticosteroid therapy intermittently for minor erosive oral disease.

Evaluation of the older cadaveric kidney donor: the impact of donor hypertension and creatinine clearance on graft performance and survival.

The use of older donors for cadaveric renal transplantation (CRT) remains controversial because older donors are associated with decreased graft survival, yet offer the opportunity for donor pool expansion. We investigated the impact of two age-related donor factors, hypertension and calculated creatinine clearance (C(Cr)), as predictors of graft outcome in recipients of CRTs from donors > or =55 years of age. We reviewed 33,595 recipients of CRTs reported to UNOS since 4/1/94, of which 4,732 were from donors aged > or =55 years. Outcome measures were graft survival, serum creatinine, and incidence of delayed graft function with 3 years of follow-up. We first analyzed the effect of hypertension on outcome from donors > or =55 years: 2679 donors had no hypertension, 1058 had hypertension < or =10 years, and 557 had hypertension > 10 years. Next, the effect of donor C(Cr) as a risk predictor was investigated. Based on this analysis, recipients of older donors were grouped into two cohorts for comparison: 2570 donors with C(Cr)<80 ml/min and 2162 donors with C(Cr) > or =80 ml/min. Actuarial graft survival from donors aged <55 years was 88.0, 83.4, and 78.5% at 1, 2, and 3 years, vs. 80.6, 73.5, and 65.3% from donors > or =55 years (P<0.0001). When stratified by hypertension, older donors hypertensive > 10 years had survivals of 77, 66, and 57% vs. 81, 73, and 65% from donors without hypertension (P<0.017) and 80, 74, and 66% from donors hypertensive <10 years (P<0.017). When stratified by C(Cr), older donors with C(Cr) <80 ml/min had survivals of 77, 69, and 62% vs. 83, 76, and 66% from donors with C(Cr) > or =80 (P<0.0001). Finally, older donors with both hypertension > 10 years and C(Cr) <80 ml/min had survivals of 77, 61, and 53%. Long-standing hypertension and low calculated creatinine clearance are risk factors for decreased graft survival of CRTs from older donors. When both factors are present, graft survival is significantly decreased.

Abdominal pain and melaena: an unusual cause

A 69-year-old Irish woman presented with a 3 week history of abdominal pain, vomiting, and intermittently dark loose stool. Similar episodes, with weight loss, had occurred over the previous 8 years, but investigations had revealed only colonic diverticulosis. Medical history included cholecystectomy, hysterectomy, and appendicectomy. She had longstanding hypertension, ischaemic heart disease, hypercholesterolaemia, and chronic renal impairment thought to be related to hypertensive nephropathy (previous serum creatinine had reached 300 μmol/L). She was an ex-smoker and was taking ramipril, simvastatin, aspirin, and omeprazole (none started within 2 months).

Clinical Advisory Statement. Importance of systolic blood pressure in older Americans.

This clinical advisory statement from the Coordinating Committee of the National High Blood Pressure Education Program is intended to advance and clarify the recommendations of the Sixth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI, 1997).1 The advisory addresses several interrelated issues about blood pressure (BP) that affect people approaching the later decades of life. On the basis of the wealth of currently available evidence, the committee now recommends a major paradigm shift in urging that systolic BP become the major criterion for diagnosis, staging, and therapeutic management of hypertension, particularly in middle-aged and older Americans. Several lines of strong evidence support the initiative to emphasize systolic BP. Pathophysiologically, there are strong associations among aging, increased stiffness of large arteries, increased systolic BP, increased pulse pressure, and the prevalence of cardiac and vascular disease. Epidemiologically, isolated systolic hypertension is the most common form of hypertension and is present in approximately two thirds of hypertensive individuals >60 years of age. Diagnostically, classification and staging of hypertension are more precise when systolic rather than diastolic BP is used as the principal criterion. Risk stratification for major complications of hypertension (stroke, myocardial infarction, heart failure, and kidney failure) is actually confounded by the use of diastolic BP; in older people with systolic hypertension, diastolic BP is inversely related to cardiovascular risk. Clinical benefits of treatment of isolated systolic hypertension include reductions in stroke, myocardial infarction, heart failure, kidney failure, and overall cardiovascular disease morbidity and mortality. Currently, only 1 in 4 Americans with hypertension falls below JNC VI–recommended values of 140/90 mm Hg in uncomplicated hypertension or 130/85 mm Hg in individuals with kidney disease or diabetes. Hypertension control rates are poorest in older people, primarily as a result of inadequate …

Strategies for improving hemodynamic stability in cardiac-compromised dialysis patients

In hemodialysis patients, structural changes at all levels of the cardiovascular system are common. The presence of these cardiovascular changes is a risk factor for the development of intradialytic hypotension. This explains the clinical observation that the incidence of symptomatic hypotension is high in elderly hemodialysis patients, who often have a history of long-standing hypertension and atherosclerosis, and in hemodialysis patients with cardiovascular disease. With an increasing number of cardiovascular compromised dialysis patients, special attention should be given to this group of patients. As the age of patients on hemodialysis increases steadily, it is a challenge to provide comfortable treatment in these patients by reducing the incidence of symptomatic hypotensive periods. This article describes the use of relatively new and simple clinical maneuvers to reduce the incidence of symptomatic hypotension.

Relative influence of insulin resistance versus blood pressure on vascular changes in longstanding hypertension. ICARUS, a LIFE sub study

Insulin resistance is associated with hypertension. The relative influences of hyperinsulinaemia and high blood pressure on vascular hypertrophy and carotid distensibility is unclear in patients with longstanding hypertension. In 88 unmedicated patients with stage II-III hypertension and left ventricular hypertrophy on electrocardiogram we measured blood pressure, minimal forearm vascular resistance (MFVR) using plethysmography, intima-media thickness (IMT) and the wall distensibility of the common carotid arteries using ultrasound, and insulin sensitivity using a 2-h isoglycaemic hyperinsulinaemic clamp. IMT was positively correlated to systolic blood pressure (r= 0.26, P < 0.05), whole body glucose uptake index (M/IG; r= 0.22, P< 0.05), age (r= 0.24, P< 0.05) and negatively correlated to body mass index (r= -0.24, P < 0.05); IMT did not correlate to fasting serum insulin (r= -0.14, NS). In men (n = 64) MFVR was positively correlated to systolic blood pressure (r = 0.30, P < 0.05), but was unrelated to M/G and serum insulin. The distensibility of the common carotid arteries was negatively correlated to systolic blood pressure (r = -0.40, P< 0.001) and in untreated patients (n = 22) positively correlated to M/IG (r = 0.47, P < 0.05). High systolic blood pressure was related to vascular hypertrophy, whereas hyperinsulinaemia and insulin resistance were not, suggesting that longstanding high blood pressure is a far more important determinant for structural vascular changes than insulin resistance at this stage of the hypertensive disease. However, hyperinsulinaemia and insulin resistance were associated with low distensibility of the common carotid arteries in the subgroup of never treated hypertensive patients.

A Possible Link Between Endothelial Dysfunction and Insulin Resistance in Hypertension. A LIFE Substudy

Background: We wanted to investigate whether insulin resistance and time to steady state during isoglycemic clamp were associated with endothelial dysfunction, peripheral vascular remodeling and forearm blood flow (FBF) in patients with longstanding hypertension. Methods: In 43 unmedicated, hypertensive patients with electrocardiographic-defined left ventricular hypertrophy we performed a 2-h oral glucose tolerance test and a 3-h isoglycemic hyperinsulinemic clamp with measurements of circulating plasma epinephrine and FBF by plethysmography. Delayed steady state was assessed by measuring the increase in insulin sensitivity from the second to the third hour of clamping. We measured 24-h ambulatory blood pressure, minimal forearm vascular resistance (MFVR) by plethysmography, media:lumen ratio (MLR) and acetylcholine-induced relaxation (AIR) in isolated, subcutaneous resistance arteries by myography. Results: Insulin sensitivity after 2 and 3h of clamping was not related to maximal AIR, MLR, MFVR or FBF. The increase in insulin sensitivity in men was negatively correlated to maximal AIR (r=-0.36, p

Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure.

It is taken for granted that patients with hypertension are at greater risk for intracerebral hemorrhage during neurosurgical procedures than patients with normal blood pressure. The anesthesiologist, therefore, maintains mean arterial blood pressure (MABP) near the lower end of the autoregulation curve, which in patients with preexisting hypertension can be as high as 110 to 130 mm Hg. Whether patients with long-standing hypertension experience more hemorrhage than normotensive patients after brain surgery if their blood pressure is maintained at the presurgical hypertensive level is currently unknown. The authors tested this hypothesis experimentally in a rodent model. Hemorrhage and edema in the brain after needle biopsy was measured in vivo by using three-dimensional magnetic resonance (MR) microscopy in the following groups: WKY rats, acutely hypertensive WKY rats, spontaneously hypertensive rats (SHR strain), and SHR rats treated with either sodium nitroprusside or nicardipine. Group differences were compared using Tukey's studentized range test followed by individual pairwise comparisons of groups and adjusted for multiple comparisons. There were no differences in PaCO2, pH, and body temperature among the groups. The findings in this study indicated that only acutely hypertensive WKY rats had larger volumes of hemorrhage. Chronically hypertensive SHR rats with MABPs of 130 mm Hg did not have larger hemorrhages than normotensive rats. There were no differences in edema volumes among groups. The brains of SHR rats with elevated systemic MABPs are probably protected against excessive hemorrhage during surgery because of greater resistance in the larger cerebral arteries and, thus, reduced cerebral intravascular pressures.

Mechanisms and efficacy of LV pre-excitation for patients with heart failure and supra-normal systolic function.

Ventricular hypertrophy due to genetic mutations of sarcomeric proteins or that associated with long-standing hypertension typically yields a cavity with hyperdynamic ejection, elevated diastolic pressures, and limited filling volumes. The net result is reduced reserve capacity, dyspnea with exertional intolerance, and chest discomfort despite normal appearing coronary vessels. In addition to pharmacologic therapy by agents having negative inotropic effects, recent studies have examined the potential of ventricular pacing using right apical pre-excitation as a treatment for these disorders. This form of pacing can increase end-systolic volume and reduce cavity obliteration in both forms of the disease, yet has no demonstrable acute benefit on diastolic function. Chronic therapy trials have yielded mixed results, with more favorable responses observed in older patients particularly those with hypertensive hypertrophic disease. These data have also highlighted the importance of enhancing systolic reserve rather than diastolic function as a key therapeutic effect from pacing therapy. This review discusses the mechanisms by which pacing with ventricular pre-excitation acutely influences ventricular function, and summarizes results of recent clinical trials, putting the data into perspective regarding the relative role of systolic versus diastolic effects in these patients.

Impaired cardiac performance in elderly patients with growth hormone deficiency.

Several evidences indicate that GH and/or insulin-like growth factor I (IGF-I) are involved in the regulation of cardiovascular function. In patients with childhood and adulthood-onset GH deficiency (GHD), the impairment of cardiac performance is manifest primarily as a reduction in the left ventricular (LV) mass (LVM), inadequacy of LV ejection fraction both at rest and at peak exercise, and abnormalities of LV diastolic filling. No study has been reported to date in elderly GHD patients that investigated cardiac function. In particular, it is unknown whether cardiac function is modified in accordance with patients' age as a physiological response to aging, as in normal subjects the rate and extent of LV filling are reduced with age. This study was designed to evaluate heart morphology and function, by echocardiography and equilibrium radionuclide angiography, respectively, in rigorously selected elderly patients with GHD but without evidence of other complications able to affect cardiac performance. Eleven patients with hypopituitarism (6 men and 5 women, aged 60-72 yr) and 11 sex- age- and body mass index-matched healthy subjects entered this study. None of the patients and controls presented with or had previously suffered from other concomitant diseases, such as diabetes mellitus, coronary artery diseases, long-standing hypertension, and hyperthyroidism, which could affect cardiac function. All patients had been previously operated on via the transsphenoidal and/or transcranic route for nonfunctioning pituitary adenoma, meningioma, or craniopharyngioma, and 6 of them had been irradiated. Eight patients had FSH/LH insufficiency, 5 had TSH insufficiency, and 6 had ACTH insufficiency, appropriately replaced. All subjects were tested with the combined arginine plus GHRH test showing a GH response below 9 microg/L. No significant difference was found in plasma IGF-I levels (49.2 +/- 8.5 vs. 71.8 +/- 7.5 microg/L) between patients and controls. However, IGF-I levels were lower than the normal range in 8 patients and 3 controls. Interventricular septum thickness (9.1 +/- 0.2 vs. 9.1 +/- 0.2 mm), LV posterior wall thickness (9.1 +/- 0.2 vs. 9.0 +/- 0.2 mm), and LVM after correction for body surface area (97.6 +/- 1.8 vs. 99.9 +/- 1.5 g/m2) were similar in patients and controls. Similarly, the LV ejection fraction at rest was similar in patients and controls (57.1 +/- 2% vs. 63.2 +/- 2.5%; P = NS), and it was normal (> or = 50%) in all controls and in 10 of 11 patients. By contrast, the LV ejection fraction at peak exercise was markedly depressed in elderly GHD patients compared to age-matched controls (51 +/- 2.5% vs. 73.3 +/- 3%; P < 0.001). A normal response (> or = 5% increase compared to basal value) of LV ejection fraction at peak exercise was found in 8 controls (72.7%) and in 2 of 11 patients (18.2%). No difference was found in the peak rate of LV filling, whether peak filling rate was normalized to end-diastolic volume (2.5 +/- 0.2 vs. 2.6 +/- 0.2 end-diastolic volume/s) or stroke volume (4.3 +/- 0.3 vs. 4.0 +/- 0.3 stroke volume/s), between patients and controls. Finally, exercise duration was significantly shorter in elderly GHD patients than in age-matched controls (7.2 +/- 2.1 vs. 9.1 +/- 0.2 min; P < 0.01). In the patient group, the GH peak after arginine plus GHRH test was significantly correlated with the LV ejection fraction at rest (r = 0.822; P < 0.01), whereas IGF-I was significantly correlated with the peak rate of LV filling whether the peak filling rate was normalized to end-diastolic volume (r = -0.863; P < 0.001) or stroke volume (r = -0.616; P < 0.05) or expressed as the ratio of peak filling rate to peak ejection fraction rate (r = -0.736; P < 0.01). Disease duration was significantly correlated with heart rate at peak exercise (r = 0.614; P < 0.05) and with systolic and diastolic blood pressures both at rest (r = 0.745; P < 0.01 and r = 0.650; P < 0.05) and at peak exercise (r = 0.684; P < 0.05 and r =

Amyloidosis: Recognition, Confirmation, Prognosis, and Therapy

Amyloidosis: Recognition, Confirmation, Prognosis, and Therapy

Extrinsic compression of the left main coronary artery by the pulmonary artery in patients with long-standing pulmonary hypertension

Left main coronary artery compression by the pulmonary artery may be seen in patients with pulmonary hypertension who are undergoing cardiac catheterization. Cardiac magnetic resonance imaging is useful in these patients to document extrinsic compression, which might otherwise be mistaken for intrinsic atherosclerotic disease.

Cardiovascular abnormalities in never-treated hypertensives according to nondipper status

Ambulatory blood pressure monitoring allows a better understanding of blood pressure fluctuations over 24 h than simple clinic measurements. In this way the diagnosis of “white coat” versus “sustained” hypertension and that of “dipper” (patient with blood pressure fall during nighttime > 10% of daytime levels) versus “nondipper” status were made possible. This pilot study has been undertaken to investigate whether patients with recently discovered, never-treated, mild, sustained hypertension have cardiovascular abnormalities according to their dipper/nondipper status. Patients with long-standing (n = 123) and newly discovered (n = 56) sustained hypertension were classified according to their nighttime blood pressure fall, and compared with normotensive controls. Ambulatory blood pressure monitoring was performed noninvasively. Parameters of left ventricular structure, cardiac systolic and diastolic function, and carotid anatomy were determined noninvasively by echographic methods. Significant increases in parameters of cardiac structure as well as abnormalities in diastolic function were observed in patients with long-standing hypertension, regardless of their dipper status. In the group with newly discovered hypertension, left atrium (3.4 ± 0.3, 3.7 ± 0.5, 3.2 ± 0.4 cm in dippers, nondippers, and controls, respectively), end-diastolic diameter index (2.9 ± 0.3, 3.0 ± 0.2, 2.8 ± 0.2 cm/m), and atrial filling fraction (0.50 ± 0.07, 0.52 ± 0.05, 0.42 ± 0.04) were significantly altered only in the nondipper subgroup, in comparison with controls. Significant changes in cardiac structure and diastolic function were observed in nondipper patients with recently discovered hypertension, who, at variance with dippers, show changes similar to those in patients with long-standing hypertension. Hypertensives with the observed abnormalities may benefit from active antihypertensive treatment, which appears, therefore, justified even in an early phase of mild hypertension, in terms of potential reduction of end-organ complications as well as cost-effectiveness.

Arterial hypertension: its impact on perioperative morbidity and mortality

Chronic hypertension is associated with structural as well as functional changes of the vasculature, in particular of the coronary, cerebral and renal circulation. It is important to realise that [1] functional changes are often the result of structural changes, [2] the longer lasting the hypertension, the slower and less complete the regression of structural changes, and [3] acute "normalisation" of arterial pressure in long-standing hypertension may initially induce functionally subnormal smooth muscle and/or cardiac activity because the structure of the cardiovascular system is adapted to function at elevated pressures. Despite a multitude of studies, the impact of hypertension on peri-operative morbidity and mortality remains controversial. There are as many studies seeming to suggest that preoperative hypertension correlates with adverse outcome as there are studies that fail to establish such a relationship. When looking at the combined evidence, one is inclined to conclude that hypertension is a predictor of "soft" outcomes (e.g. peri-operative myocardial ischaemia and transient post-operative neurologic deficit) rather than an independent predictor of "hard" outcomes (e.g. unstable angina, myocardial infarction and cardiac death). In view of lack of convincing outcome data, it is impossible to recommend a generally acceptable management strategy for the hypertensive patient. Although, in general, a gradual reduction of blood pressure over a period of weeks to months is the optimal therapeutic approach, we will be hard-pressed delaying surgery for the sole purpose of "better blood pressure control". With full appreciation and detailed knowledge of the pathophysiology of hypertension, combined with sophisticated haemodynamic monitoring and interventions in the peri-operative period, acutely anaesthetising an inadequately treated hypertensive patient will probably not adversely affect his outcome. Delaying surgery for additional work-up may possibly improve outcome in patients with target organ disease, evidence of secondary hypertension, in the most severe forms of hypertension or sudden-onset hypertension.

Recursive Partitioning for the Identification of Disease Risk Subgroups: A Case-Control Study of Subarachnoid Hemorrhage

Recursive partitioning is a nonparametric technique that produces a classification tree in which subjects are assigned to mutually exclusive subsets according to a set of predictor variables. We examined the utility of recursive partitioning as a supplement to logistic regression for the multivariable analysis of data from case-control studies, demonstrating the technique using data from women enrolled in a population-based study of subarachnoid hemorrhage. The classification tree produced by recursive partitioning consisted of three main risk subgroups: (1) elderly women who had long-standing hypertension and who were not smokers, (2) middle-aged women who were cigarette smokers and frequent binge drinkers, and (3) women in whom risk variables indicate relative estrogen deficiency (i.e., postmenopausal status, no recent exposure to hormone replacement therapy, cigarette smoking). As a supplemental method, recursive partitioning not only identifies subgroups with varying risks, but also may uncover interactions between variables that may be overlooked in the traditional application of logistic regression to case-control data.