Atrial Natriuretic Factor Response to Acute Volume Expansion in Borderline Hypertension. Role of Ace-Inhibition and Changes in Peripheral Venous Tone

Abnormalities in the response of atrial natriuretic factor (ANF) to volume expansion have been reported in hypertensive-prone animals and men as well as in hypertensive patients undergoing ACE-inhibition. To investigate some of the mechanisms affecting ANF release in borderline hypertensive patients (BHT) we have studied 16 subjects by assessing their neuro-humoral and hemodynamic response to a two-hour isotonic i.v. NaCl infusion carried out during short-term administration of either placebo or captopril. ACE-inhibition increased baseline venous distensibility (VV₃₀:1.4 vs 1.6 ml/100 ml;p<.05) and reduced the prompt (45′) ANF response to saline loading (10.3±13 vs 42.7±15%;p<.05)) without affecting the overall ANF release (120′:92±25 vs 65.8±20%;NS)). A significant pressor increase in response to NaCl loading was observed exclusively after ACE-inhibition (SBP:5.2±2 vs 2.4±1%; p < .05 - DBP:7.1±3 vs 2±3%; p < .025) and occurred along with a peripheral arterial and venous constriction and with an increase in plasma levels of an endogeneous Na⁺/K⁺ ATPase inhibitor (8.8 ± 4 vs ?2±4%; p <.05). We conclude that the ANF response to saline infusion is delayed by ACE-inhibition in borderline hypertensives. The abnormalities observed in ANF response could follow the changes in peripheral venous distensibility and contribute to the pressor and neuro-humoral derangements described in borderline hypertensives during volume expansion.     

Conservative surgical approach versus non-surgical management for diabetic neuropathic foot ulcers: a randomized trial

To test the efficacy of surgical treatment of non-infected neuropathic foot ulcers compared to conventional non-surgical management, a group of diabetic outpatients attending our diabetic foot clinic were studied. All patients who came to the clinic for the first time from January to December 1995 inclusive with an uncomplicated neuropathic ulcer were randomized into two groups. Group A received conservative treatment, consisting of relief of weight-bearing, regular dressings; group B underwent surgical excision, eventual debridement or removal of bone segments underlying the lesion and surgical closure. Healing rate, healing time, prevalence of infection, relapse during a 6-month period following intervention and subjective discomfort were assessed. Twenty-four ulcers in 21 patients were treated in group A (17 Type 2 DM/3 Type 1 DM, age 63.24 ± 13.46 yr, duration of diabetes 18.2 ± 8.41 yr, HbA_1c 9.5 ± 3.8%) and 22 ulcers in 21 patients in group B (19 Type 2 DM/2 Type 1 DM, age 65.53 ± 9.87 yr, duration of diabetes 16.84 ± 10.61 yr; HbA_1c 8.9 ± 2.2%). Healing rate was lower (79.2% = 19/24 ulcers) in group A than in group B (95.5% = 21/22 ulcers; p < 0.05), and healing time was longer (128.9 ± 86.60 days vs 46.73 ± 38.94 days; p < 0.001). Infective complications occurred significantly more often in group A patients (3/24, 12.5% vs 1/22, 4.5%; p < 0.05), as did relapses of ulcerations (8 vs 3; p < 0.01). There were only two minor perioperative complications in group B patients. Patients reported a higher degree of satisfaction in group B (p < 0.01) as well as lower discomfort (p < 0.05) and restrictions (p < 0.05). Thus surgical treatment of neuropathic foot ulcers in diabetic patients proved to be an effective approach compared to conventional treatment in terms of healing time, complications, and relapses, and can be safely performed in an outpatient setting. © 1998 John Wiley & Sons, Ltd.     

The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism*

OBJECTIVE The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established but much less is known about its action on the adult skeleton. We therefore wished to investigate the effects of replacement treatment with blosynthetic human GH in hypopituitary adults on aspects of calcium homeostatis, bone metabolism and bone mineral mass. PATIENTS Forty hypopituitary adults (21 females and 19 males; aged 19–67 years). DESIGN A prospective randomized double-blind placebo-controlled trial lasting for 6 months. PROTOCOL Following baseline assessments, GH was given in a daily dose of 0·02–0·05 IU/kg body weight subcutaneously (or a placebo (P)) at bedtime. Patients were reviewed at 1, 3 and 6 months. MEASUREMENTS Plasma calcium, phosphate and total plasma alkaline phosphatase were measured at 0, 1, 3 and 6 months. Serum insulin like growth factor I (IGF-I), osteocalcin, procollagen 1 carboxyterminal peptide (P1CP) and intact parathyroid hormone (PTH) level, 24-hour urinary calcium and creatinine excretion were all measured at 0 and 6 months. Bone mineral density of total body and lumbar spine was also measured by dual energy X-ray absorptiometry at 0 and 6 months in 12 patients on GH and 14 on placebo. RESULTS Thirty-eight patients completed the study (18 on GH, 20 on placebo). Serum IGF-I Increased significantly on GH treatment (mean ± SD) (GH: 276 ± 197 vs P: 88 ± 50 μg/l, P < 0 0001 at 6 months). Plasma calcium increased slightly but significantly in the GH-treated group (2·23 ± 0·11–2·29 ± 0·11 mmol/l, P<0·05). At the end of the study, plasma calcium was however similar on GH and placebo (GH, 2·29 ± 0·11; P, 2·26 ± 0·09 mmol/l). Plasma phosphate increased on GH (GH: 1·02±0·23–1·32±0·19; P: 0·99±0·16–0·96±0·12 mmol/l over the 6 months of treatment, P<0·001). There was no significant change in the urinary calcium excretion on GH therapy. Plasma total alkaline phosphatase, osteocalcin and P1CP were significantly higher on GH than P at 6 months (alkaline phosphatase: GH: 104±32 vs P: 69±32 U/I, P<0·01, osteocalcin: GH: 17·2±8·0 vs P: 5·3±3·2 μg/l, P<0·001 and P1CP: GH: 207 ± 152 vs P: 93±31 μg/l, P<0·01). There was no difference in the intact parathyroid hormone level (GH: 31 ± 14 vs P:31 ± 15 ng/l, NS). No significant change was observed in bone mass after 6 months of GH treatment, either in total body bone mineral content or in the lumbar spine. CONCLUSION In this large study, GH replacement in hypopituitary adults for 6 months increased bone turnover but did not affect bone mineral content. Longer-term studies are required to assess further any effect on bone mass.     

Growth Hormone Levels in Patients with Type 1 Diabetes are Age Related

Possible effects of age on the growth hormone (GH) levels in Type 1 diabetes were examined. The study was performed in 71 patients with Type 1 diabetes (40 C-peptide negative (CpN), without residual beta cell activity; 31 C-peptide positive (CpP), with preserved beta cell activity) and 11 healthy subjects. The patients and controls were divided into three age groups (A = 21–30; B = 31–40; C = 41–50 years). Blood glucose and growth hormone (GH) were measured at hourly intervals during 24 h in all subjects in hospital conditions. GH levels decreased significantly with age in patients with Type 1 diabetes (mean 24-h GH group A: 7.3 ± 1.0, group B:5.3 ± 0.6, group C:3.7 ± 0.4 mU 1^?1; A vs C: p = 0.0007; B vs C: p = 0.03). In all age groups GH levels were significantly higher in CpN than either in CpP diabetic patients or controls (group A CpN: 8.3 ± 1.2, CpP: 4.7 ± 1.0, controls: 2.2 ± 0.3 mU 1^?1; p < 0.001; group B CpN: 7.3 ± 0.8, CpP: 3.2 ± 0.5, controls: 1.6 ± 1.0 mU 1^?1; p < 0.0002; group C CpN: 5.2 ± 0.5, CpP: 2.5 ± 0.4, controls: 1.4 ± 0.4 mU 1^?1; p < 0.001). Mean GH levels were significantly higher in C-peptide positive patients than in controls in all age groups (p < 0.001). GH levels decreased with age in patients with diabetes and controls, but the decrease was significant only in patients with diabetes (A vs C CpN: p = 0.018, CpP: p = 0.026). We conclude that age is a factor in addition to residual beta cell activity, which influences the magnitude of GH hypersecretion in Type 1 diabetes.     

Catecholamines,Angiotensin II and Sodium Concentrations in Cerebrospinal Fluid in Young Men with Borderline Hypertension

To evaluate the role of central nervous mechanisms and their relationships to the peripheral sympathetic nervous system in borderline hypertension, we measured catecholamines, angiotensin II (AII) and sodium (Na) concentrations in cerebrospinal fluid (CSF) with plasma catecholamines concomitantly in 12 young men with borderline hypertension and 7 age-matched healthy normotensive men on ordinary salt intake. Plasma norepinephrine (NE) and epinephrine (E) were higher in the borderline hypertensives than in the normotensives (NE: 239 ± 15 vs 190 ± 11 pg/ml, p < 0.05, E: 83 ± 9 vs 43 ± 6 pg/ml, p < 0.01). NE levels in CSF were also higher in the borderline hypertensives than in the normotensives (200±15 vs 150 ± 18 pg/ml, p < 0.05). In most of the subjects, CSF E and plasma and CSF dopamine levels were below the sensitivity of the assay. CSF NE correlated positively with both plasma NE (p < 0.01) and mean blood pressure (p < 0.05) in all subjects. Immunoreactive All and Na concentrations in CSF did not differ between the borderline hypertensives and normotensives. These results suggest that peripheral sympathoadrenal overactivity in young subjects with borderline hypertension may be related to an altered function of central noradrenergic neurons. A11 and Na in the central nervous system do not appear to have an important role in borderline hypertension     

Factors Related to the Electric Taste Threshold in Type 1 Diabetic Patients

To specify the factors related to taste function in Type 1 diabetes mellitus, 50 diabetic out-patients and 50 control subjects paired for age and sex were screened for taste disorders. None of them consumed significant amounts of alcohol, smoked, or had disease or took drugs capable of altering taste. Taste was studied with electrogustometry, retinopathy was detected by fluorescein angiography, nephropathy by measurement of albuminuria and microalbuminuria, peripheral neuropathy by electroneurography and electromyography, and autonomic neuropathy by cardiovascular function tests. The electrogustometric threshold was, on average, significantly higher in the diabetic group (133 ± 30 μA) than in the control group (29 ± 9 μA; p < 0.001). Electric hypogeusia (electrogustometric threshold > 100 μA) was found among 54% of the diabetic patients vs 2% of the control subjects (p < 0.001). In the diabetic group, the electrogustometric threshold was associated with complications of diabetes, especially with peripheral neuropathy (210 ± 24 vs 90 ± 22 μA; p < 0.001) and microalbuminuria (185 ± 25 vs 86 ± 21 μA; p < 0.01). It was correlated with age (r = 0.37; p < 0.01) and duration of diabetes (r = 0.52; p < 0.001) but not with HbA_1c (r = ?0.04). Using multivariate analysis, duration of diabetes and peripheral neuropathy had the strongest association with taste impairment. These results support previous findings, suggesting that taste impairment is a degenerative complication of diabetes mellitus.     

Increased Red Cell Aggregation in Diabetes Mellitus: Association with Cardiovascular Risk Factors

Red cell aggregation may be higher in diabetic patients and may predispose to cardiovascular disease. Red cell aggregation was measured by a simple photometric method in 122 diabetic patients and 100 matched control subjects, to determine its relationship to cardiovascular risk factors. Red cell aggregation was significantly increased in both Type 1 (4.3 ± 1.3 vs 3.4 ± 1.2, p < 0.002) and Type 2 diabetic patients (5.5 ± 1.5 vs 3.2 ± 1.3, p < 0.0001). In all diabetic patients aggregation correlated with triglycerides, VLDL, and inversely with HDL and in Type 2 diabetic patients also with body mass index, hypertension, and inversely with duration of diabetes. On multiple regression analysis, triglycerides and body mass index showed an independent association with red cell aggregation and in Type 2 diabetic patients smoking was also associated with increased red cell aggregation. It is concluded that increased red cell aggregation may be one mechanism by which some cardiovascular risk factors could promote cardiovascular disease in diabetes.     

Insulin Deficiency Rather Than Hyperinsulinaemia in Newly Diagnosed Type 2 Diabetes Mellitus

This paper reports beta cell function as assessed during OGTT using specific IRMAs for insulin, intact and 32/33 split proinsulin in subjects with newly diagnosed Type 2 diabetes matched to normal controls. The relationships between insulin and the proinsulins to risk factors for cardiovascular disease were also examined. Similar fasting insulin concentrations but lower 30-min post-glucose-load insulin concentrations were found in diabetic subjects (mean ± SEM 143 ± 12 pmol^?1 vs 304 ± 19 (p < 0.001). Subjects with diabetes had increased fasting intact (10.6 ± 1.1 pmol^?1 vs 3.3 ± 0.2, p < 0.001) and 32/33 split proinsulin concentrations (8.1 ± 0.9 pmol^?1 vs 2.2 ± 0.3, p < 0.0001). Beta cell dysfunction, as expressed by a reduction in the 30-min insulin to glucose ratio (9.4 ± 1 vs 34.8 ± 2.3, p < 0.0001) and an increase in the fasting percentage of total proinsulin-like to total insulin-like molecules (24.5 ± 9% vs 11.6 ± 5, p < 0.001), was present in subjects with diabetes. In diabetic subjects beta cell dysfunction and insulin deficiency increased relative to the degree of fasting hyperglycaemia. It seems clear that beta cell dysfunction and insulin deficiency are major features of Type 2 diabetes. Only the fasting concentration of 32/33 split proinsulin positively correlated with both the waist/hip ratio (r = 0.36, p < 0.001), diastolic blood pressure (r = 0.23, p < 0.01) in addition to plasma triglyceride concentration (r = 0.46, p < 0.001). It is questionable whether hyperinsulinaemia plays a pathogenic role in cardiovascular disease in subjects with glucose intolerance.     

Excessive pulse pressure response to standing in community population with orthostatic systolic hypertension

The postural change of pulse pressure (PP) in the persons with orthostatic hypertension (OHT) is unclear. This study included 2849 (65.0 ± 9.3 years) community participants. Blood pressures (BPs) in supine and standing positions were measured. The differences between upright and supine BP and PP were recorded as ΔBP and ΔPP. The criteria for OHT was ΔBP ≥10 mm Hg, for orthostatic hypotension (OH) was ≤−10 mm Hg and for orthostatic normotension (ONT) was −9 to 9 mm Hg. Fasting blood lipids and glucose were measured. The supine SBP of the sOHT group were similar to that of sONT group (140.9 ± 20.2 mm Hg vs 138.2 ± 19.7 mm Hg), but significantly lower than that of sOH group (151.9 ± 19.2 mm Hg; P < .05). Their PPs were 65.3 ± 15.9, 62.8 ± 14.7, and 71.1 ± 15.1 mm Hg, respectively, and with the similar group difference like SBP. When the position changed from supine to standing, the sOHT group showed PP rise, while sOH and sONT groups showed PP reduction (3.8 ± 7.1 mm Hg vs −17.0 ± 8.5 mm Hg and −5.8 ± 6.6 mm Hg; both P < .05). Thus, the standing PP in the sOHT group was significantly higher than in the sONT (69.1 ± 18.0 mm Hg vs 57.0 ± 15.8 mm Hg; P < .05) and in the sOH (54.2 ± 15.2 mm Hg; P < .05) groups. The postural PP profile varies with the postural responses of SBP. The sOHT group has obviously increased PP and significantly higher standing PP compared with the sONT group.     

Serial plasma catecholamine response early in the course of clinical acute myocardial infarction: Relationship to infarct extent and mortality

Clinical and experimental evidence suggest that sympathoadrenal activation contributes to mortality in patients with ischemic heart disease. To determine the level of sympathoadrenal activation in the very early phase of acute myocardial infarction (AMI) and to determine if location of infarction (anterior versus inferior) was related to sympathoadrenal activation, we studied norepinephrine (NE) and epinephrine (E) within 4 hours after the onset of symptoms and prior to any rise in plasma creatine kinase (CK). Mean (± SE) initial (NE = 591 ± 111 pg/ml and E = 73 ± 19 pg/ml), peak (NE = 1356 ± 178 and E ± 1098 ± 608) and average (NE = 815 ± 142 and E = 252 ± 68) plasma catecholamine concentrations were considerbly above normal (NE = 228 ± 10 and E = 34 ± 2 pg/ml, n 60) and values were similar for inferior and anterior infarctions. During an 18-month follow-up, three patients died in whom the AMI mean NE and E and peak CK were higher than in the eight late survivors. Thus the three AMI patients with peak EP values > 1000 died, whereas the eight AMI patients with peak EP values < 1000 survived (p < 0.01). The magnitude of sympathoadrenal activation early in the course of clinical AMI appeared related to the extent of myocardial damage and late mortality.     

Suppression of prolactin and growth hormone responses to 2-deoxy-D-glucose-induced glucoprivation by mazindol in humans

Glucoprivation induced by 2-deoxy-D-glucose (2DG) 20 min infusions (50 mg/kg) increases growth hormone (GH) and prolactin (PRL) levels in humans. To determine if mazindol, a potent dopamine (DA) and norepinephrine (NE) reuptake blocking agent, might affect basal and stimulated GH and PRL levels in healthy male and female volunteers, mazindol (1 mg,TID,po) or placebo were administered for one week before 2DG infusions. Plasma samples for glucose, epinephrine (E), NE, PRL, and GH were collected before and after 2DG infusions. During placebo and mazindol therapy, basal values (ng/ml) did not differ for either PRL (8.8 ± 1.6 versus 8.9 ± 1.5 in females and 8.3 ± 0.9 versus 7.7 ± 0.6 in males) or GH (1.6 versus 1.7 ± 0.1 in males and 6.6 ± 3.3 versus 7.0 ± 2.6 in females). Peak stimulated PRL levels were greater in females than in males (97.1 ± 26.2 versus 21.4 ± 5.3 ng/ml, p < 0.05) while peak stimulated GH levels were greater in males than in females (28.2 ± 1.7 versus 7.0 ± 2.0 ng/ml, p < 0.05). Mazindol therapy reduced 2DG-stimulated PRL responses (ng/ml) from 97.1 ± 26.2 to 44.4 ± 25.3 (p < 0.0125) and from 21.4 ± 5.3 to 13.6 ± 3.4 (p < 0.025) in females and males respectively, and GH responses (ng/ml) from 28.2 ± 1.7 to 13.1 ± 3.8 (p < 0.05) and from 10.2 ± 2.0 to 3.4 ± 0.1 (p < 0.05) in males and females respectively, but baseline PRL and GH levels were unaffected. A 50%–60% overall suppression of stimulated GH and PRL levels by mazindol was not significantly different between sexes and not consistently related to elevations in plasma glucose or E although stimulated plasma NE levels were higher during mazindol therapy.     

Prolonged ambulant assessment of anorectal function in patients with prolapsing hemorrhoids

Six patients with prolapsing hemorrhoids and 12 control subjects had assessment of anorectal pressure and external sphincter electromyography performed over a prolonged period under ambulant conditions. Patients with prolapsing hemorrhoids demonstrated greater degrees of sampling responses, 12.9±1.9/hour,vs. 7.4±2.0/hour (mean ±SEM) in controls (P<.05). Ultraslow wave and giant ultraslow wave activity were seen frequently in the patient group occupying more than 30 percent of recording. The external sphincter demonstrated much greater electrical activity (spike potentials) in patients with hemorrhoids than in controls both by day, 24.9±11.0/10 minvs. 12.8±3.2/10 min (P<.02), and by night, 7.4±2.6 minvs. 1.6 ±1.3/10 min (P<.03). Sleep electrical activity in the presence of hemorrhoids did not differ significantly from that of controls during waking, 7.4±2.6/10 minvs. 12.8±3.2/10 min (P<.1). No difference in phasic and periodic rectal motor activity was noted between patient and control groups. This demonstrates the application of prolonged assessment of anorectal motility and external sphincter activity in a patient group. Abnormalities previously documented in patients with hemorrhoids using conventional manometric tests were confirmed. In addition, evidence of increased external sphincter function during waking and sleep may have implications in the pathophysiology of this disorder.     

Modulation of Electrical Microvolt Level T‐Wave Alternans and Left Ventricular Late Potentials Evaluated by Heart Rate Variability Indices,QT Dispersion,and Plasma Catecholamine Levels

Objective: The purpose of this study was to investigate how the modulation of electrical microvolt level T‐wave alternans (Twa) relates to left ventricular late potentials as evaluated by heart rate variability (HRV), QT dispersion, and plasma catecholamine levels. Background: The Twa and left ventricular late potentials are promising noninvasive powerful markers for risk prediction in patients with ischemic heart disease (IHD) and/or cardiomyopathy. However, their relation to autonomic activity is unclear. Methods: In 56 patients with stable IHD‐measured Twa at rest and during controlled bicycle ergometer testing, we simultaneously recorded recent noninvasive electrocardiographic approaches, such as HRV, QT dispersion, and left ventricular late potentials. Plasma norepinephrine (NE) and epinephrine (E) were also measured. Results: (1) There were no significant differences in clinical findings, NE, and E levels between positive (group A) and negative (group B) Twa. Left ventricular late potentials, LF (low frequency spectra), as well as HF (high frequency spectra) in group A were significantly lower than in group B, but LF/HF did not differ significantly between the two groups. There was a significant inverse correlation between Twa microvoltage and LF/HF that was higher during exercise (r = ‐0.51, P = 0.006) than at rest (r = ‐0.34, P < 0.01). (2) There were no significant differences in clinical findings between positive (group C) and negative (group D) left ventricular late potentials. Plasma NE in group C was significantly higher than in group D (1060 ± 429 pg/mL vs 395 ± 219, P < 0.05). Furthermore, LF/HF in group C was significantly lower than in group D (0.96 ± 0.27 vs 1.1 ± 0.11, P < 0.05). There were no significant correlations between left ventricular late potential parameters and QT or QT_c dispersion. Conclusions: The Twa microvoltage in patients with stable IHD exhibits similar physiologic conditions as in patients with lower HRV indices. The presence of left ventricular late potentials might be affected by sympathetic nerve modulation.     

Very low density lipoprotein subfractions in Type II diabetes mellitus: alterations in composition and susceptibility to oxidation

Aims/hypothesis. Type II (non-insulin-dependent) diabetes mellitus is associated with raised triglycerides and increased very low density lipoprotein cholesterol. The aim of this study was to assess if very low density lipoprotein subfraction composition and potential to oxidise were altered in this condition.¶Methods. Very low density lipoprotein was separated into four subfractions (A→D) by a novel, rapid ultracentrifugation procedure. Analysis of each subfraction included lipid and fatty acid composition. Preformed peroxides were measured spectrophotometrically and conjugated dienes were used as an indicator of in vitro lipid oxidation.¶Results. In all results we compared patient and control subfractions. Mean fasting plasma glucose was 8.9 ± 2.0 mmol/l in patients vs 5.1 ± 0.4 mmol/l in control subjects (p < 0.001); patient HbA_{1 c} was 7.6 ± 1.4 %. Patient total lipid standardised for apo B was higher than controls in subfractions A, B and C; A, 201 vs 60; B, 191 vs 40; C, 63 vs 21; D, 29 vs 34 μmol lipid per mg apo B (p < 0.05). Preformed peroxides were higher in all patient subfractions compared with controls: A, 340 vs 48; B, 346 vs 42; C, 262 vs 28; D, 54 vs 16 nmol per mg apo B (p < 0.001). Patient subfractions A and D were more susceptible to in vitro oxidation. Monounsaturated fatty acids were lower in patients subfractions, 35.2 vs 36.7; B, 35.1 vs 38.7; C, 34.4 vs 36.5; D, 33.0 vs 35.5 as per cent total (p < 0.05).¶Conclusions/interpretation. These results indicate abnormalities in very low density lipoprotein subfraction composition and oxidation profile in Type II diabetic subjects, which are characteristic of more atherogenic particles and that may contribute to the development of cardiovascular disease in these patients. [Diabetologia (2000) 43: 485–493]     

Early cardiovascular remodelling in Fabry disease

Aims

Fabry disease (FD) is a rare X-linked genetic disorder caused by the deficiency or absent activity of lysosomal α-galactosidase A. Cardiovascular remodelling is a hallmark of FD. The present study aimed to comprehensively evaluate the cardiac, vascular and microvascular status in a population of patients with genetic mutations for FD without left ventricular hypertrophy (LVH).

Methods and results

This study includes subjects carrying genetic mutations for FD (Fabry disease mutation-carrier, FDMC) without LVH (n?=?19). A group of control subjects (n?=?19) matched for age, sex, body mass index and cardiovascular risk factors were also included. All subjects underwent echocardiography, carotid ultrasound scan, endothelial flow-mediated dilatation (FMD) and nailfold capillaroscopy (NFC) assessment. When compared to the subjects in the control group, FDMC patients showed significantly lower mean values of systolic myocardial velocity (7.33?±?1.28 vs. 10.08?±?1.63 cm/s, p?<?0.0001), longitudinal systolic strain (?18.07?±?1.72 vs. ?21.15?±?2.22 %, p?<?0.0001), significantly higher E/E’ mean values (7.15?±?1.54 vs. 5.98?±?1.27, p?=?0.016) and intima-media thickness mean values (0.80?±?0.20 vs. 0.61?±?0.19 mm, p?=?0.005), significantly lower FMD (8.3?±?4.6 vs. 12.2?±?5.0 %, p?=?0.02), more atypical capillaries and irregular NFC architecture in FDMC than control subjects (52.6 vs. 0 %, p?<?0.0001; 78.9 vs. 36.8 %, p?=?0.02 respectively).

Conclusions

FD progressively involves cardiac, macrovascular and microvascular systems in an early stage. These features are present even in asymptomatic mutation carriers without LVH.     

Risk of preangioplasty occlusion and myocardial infarction in one-vesseldisease patients scheduled for percutaneous transluminal coronary angioplasty

Coronary occlusion or myocardial infarction occurred in 50 of 394 (13%) one-vesseldisease patients awaiting percutaneous transluminal coronary angioplasty (PTCA). To identify risk factors for these events, we first matched the 37 patients whdemonstrated occlusion on the immediate preangioplasty repeat angiogram with 37 patients who did not. Matching was based on the time interval between angiograms, the date of the procedure, and the site of the lesion. Preangioplasty occlusion patients did differ from controls by age (47 ± 11 vs 54 ± 8 years, P< <.01), smoking status (34/37 vs 24/37, P <.01), and angina class (2.6 ± 1.0 vs 2.3 ± 0.7, P < .10) at the time of the first angiogram. Second, we pooled the data of the 37 preangioplasty occlusion patients with those of the 13 patients with preangioplasty myocardial infarction. The 50 cases with complication (coronary occlusion or myocardial infarction) were younger (47 ± 12 vs 54 ± 8 years, P < .01), more often smokers (42/50 vs 24/37, P <.05), and more symptomatic (2.7 ± 0.8 vs 2.3 ± 0.7, P <.05) than the 37 controls. This study suggests that young smokers with severe angina are at high risk of preangioplasty occlusion and/or myocardial infarction; prompt management of these patients, when considered for PTCA, seems advisable.     

Are Reciprocal Changes a Consequence of “Ischemia at a Distance” or Merely a Benign Electrical Phenomenon? A Pulsed‐Wave Tissue Doppler Echocardiographic Study

Objectives: The aim of the present study was to investigate whether ST segment depression in precordial leads at the time of acute inferior myocardial infarction represents a reciprocal change rather than concurrent anterior wall ischemia on the surface electrocardiography. Background: The mechanism of reciprocal ST segment depression during acute myocardial infarction is controversial. “Ischemia at a distance” or a benign electrical phenomenon has been implicated in numerous reports. Pulsed‐wave tissue Doppler (PWTD) echocardiography can be used to examine the regional diastolic motion of the left ventricular myocardial wall and may allow the detection of ischemic segments. Methods: We evaluated regional myocardial ischemia using PWTD echocardiography in 48 patients with a first inferior wall myocardial infarction. The left ventricle was divided into 16 segments. PWTD echocardiographic velocities were obtained from each left ventricular segments. Results: Reciprocal ST segment depression was present in 35 patients (Group 1) but not in the remaining 13 patients (Group 2). There were no significant differences between groups 1 and 2 with respect to systolic (S) (7.4 ± 1.1 vs 6.8 ± 0.9 cm/s; P > 0.05), early (E) (10.5 ± 2 vs 9.4 ± 1.2 cm/s; P > 0.05), and late (A) (9.5 ± 3.2 vs 8.5 ± 2.3 cm/s; P > 0.05) diastolic waves peak velocities, E/A ratio 1.1 ± 0.2 vs 1.1 ± 0.1; P > 0.05), Ewave deceleration time (DT) (92 ± 17 vs 101 ± 16 ms; P > 0.05) and regional relaxation time (RT) (82 ± 19 vs 93 ± 21 ms; P > 0.05) in anterior wall (basal levels), which correspond to reciprocal ST segment depression on electrocardiography. According to E/A ratio detected by PWTD echocardiography in anterior wall and anterior septum, patients with reciprocal ST segment depression were also divided into two groups: Group A, with E/A ratio > 1; Group B, with E/A ratio < 1. Among the 35 patients with reciprocal ST segment depression, anterior wall ischemia was present in 10 patients and absent in 25 patients, whereas anterior septal ischemia was present 12 patients and absent in 23 patients. Conclusions: Reciprocal ST segment depression during the early phases of inferior infarction is an electrical reflection of primary ST segment elevation in the area of infarction.     

Blood Pressure Response to Sodium Restriction and Potassium Supplementation in Healthy Normotensive Children

To examine the effects of dietary sodium on blood pressure 149 healthy, normotensive children (64 males, 85 females) participated in a study to restrict sodium intake to 60 mEq/day or half of the usual intake for 3 months. Sodium excretion was significantly decreased during the study period (100.6 ± 3.4 mEq vs 46.5 ± 2.0 mEq, P<.001). As a group there was no significant change in systolic and a small decrease in diastolic blood pressure (54.2 ± 0.8 mmHg vs 53.0 ± 0.7 mmHg, p<.03, one tailed). Adjustment of blood pressure for weight and age and analysis of residuals yielded significant decreases in both mean arterial (p <.05) and diastolic blood pressure (p<.05). In the potassium supplement study, comparison of supplementation to post-supplement periods in 31 children (13 male, 18 female) showed a significantly lower (p <.05) systolic blood pressure during supplementation (101.3 ± 2.1 mmHg vs 103.3 ± 20 mmHg). Analyses of diastolic pressures, sodium excretion and weight were not significant. These studies show heterogeneity in the blood pressure response to sodium restriction and suggest that sodium restriction and potassium supplementation have different effects on blood pressure in children.     

Differences in Blood Volume Components Between Hyporesponders and Responders to Erythropoietin Alfa: The Heart Failure With Preserved Ejection Fraction (HFPEF) Anemia Trial

BackgroundHyporesponders to erythropoietin-stimulating agents (ESAs) have been associated with an increased subsequent risk of death or cardiovascular events. We hypothesized that subjects who are hyporesponsive to erythropoietin alfa would have higher plasma volumes and lower red cell deficits than subjects who are responsive to therapy.MethodsAs part of a prospective, single blind, randomized, placebo-controlled study comparing erythropoietin alfa with placebo in older adults (n = 56) with heart failure and a preserved ejection fraction (HFPEF), we performed blood volume analysis with the use of an indicator dilution technique with ¹³¹iodine-labeled albumin. We evaluated differences in plasma volumes and red cell volumes in hyporesponders (eg, <1 g/dL increase in hemoglobin within the first 4 weeks of treatment with erythropoetin alfa) compared with subjects who were responders and controls.ResultsNine of 28 subjects (32%) assigned to ESA were hyporesponders. Hyporesponders did not differ from responders nor control subjects by any baseline demographic, clinical, or laboratory parameter, including hemoglobin. Hyporesponders had a greater total blood volume expansion (1,264.7 ± 387 vs 229 ± 206 mL; P = .02) but less of a red cell deficit (?96.2 ± 126 vs ?402.5 ± 80.6 mL; P = .04) and a greater plasma volume expansion (+1,360.8 ± 264.5 vs +601.1 ± 165.5 mL; P = .01). Among responders, the increase in hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume (r = 0.91; P < .0001) as well as a decline in plasma volume (r = ?0.55; P = .06).ConclusionsAmong older adults with HFPEF and anemia, hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia, suggesting that blood volume analysis can identify a cohort likely to respond to therapy.     

Comparison of laboratory and ambulatory measures of central blood pressure and pulse wave reflection: hitting the target or missing the mark?

Prior studies demonstrating clinical significance of noninvasive estimates of central blood pressure (BP) and pulse wave reflection have relied primarily on discrete resting measures. The aim of this study was to compare central BP and pulse wave reflection measures sampled during a single resting laboratory visit against those obtained under ambulatory conditions. The secondary aim was to investigate the reproducibility of ambulatory central BP and pulse wave reflection measurements. Forty healthy participants (21 males; 24 ± 3 years) completed three measurements of brachial artery pulse wave analysis (Oscar 2 with SphygmoCor Inside) in the laboratory followed by 24 hours of ambulatory monitoring. Seventeen participants repeated the 24-hour ambulatory monitoring visit after at least 1 week. Ambulatory measures were divided into daytime (9 AM–9 PM), nighttime (1 AM–6 AM), and 24-hour periods. Compared with laboratory measurements, central systolic BP, augmentation pressure, and augmentation index (with and without heart rate normalization) were higher (all P < .01) during daytime and 24-hour periods but lower during the nighttime period (all P < .001). The drop in nighttime brachial systolic BP was larger than central systolic pressure (Δ ?20 ± 6 vs. ?15 ± 6 mm Hg; P < .0001). Repeat ambulatory measurements of central BP and pulse wave reflection displayed good-to-excellent intraclass correlation coefficients (r = 0.58–0.86; all P < .01), although measures of pulse wave reflection had higher coefficients of variation (14%–41%). The results highlight absolute differences in central BP and pulse wave reflection between discrete laboratory and ambulatory conditions. The use of ambulatory measures of central BP and pulse wave reflection warrant further investigation for clinical prognostic value.