Correlates of diastolic filling abnormalities in hypertension: a Doppler echocardiographic study

Hypertension and aging are both associated with changes of left ventricular (LV) diastolic filling and increased LV mass. To determine whether diastolic filling abnormalities are present in hypertension independent of aging and significant hypertrophy, we studied 19 hypertensive patients following a period of 4 weeks when they were not receiving therapy and 18 normotensive subjects matched for sex, age, and LV mass. All subjects had normal systolic function and ejection fraction as assessed by radionuclide angiography. We measured peak velocity of early filling (E), late filling (A), and their ratio (E/A) by Doppler echocardiography. Filling indices were abnormal in hypertensive patients, but none of the filling indices were significantly correlated with LV mass. E was inversely related to age (r = -0.62; p less than 0.01) and diastolic blood pressure (r = 0.45; p less than 0.05) in normotensive individuals, but these correlations were not significant in hypertensive patients. E was not significantly correlated to LV mass or wall thickness. In contrast, A was influenced by septal wall thickness and blood pressure in both groups. E/A correlated inversely with age in both normal individuals (r = -0.74) and hypertensive patients (r = -0.51). These findings indicate that diastolic filling abnormalities in hypertension are not solely caused by either LV hypertrophy or by aging and therefore must be in part related to the hemodynamic load or altered myocardial or chamber properties.     

The role of CGRP and afferent nerves in the modulation of pancreatic enzyme secretion in the rat

Summary Conclusion Stimulation of pancreatic sensory nerves by capsaicin produced secretory effects probably caused, at least in part, by the release of CGRP. Background In the pancreas calcitonin gene-related peptide (CGRP) has been localized in the sensory nerves, but its physiological role is unknown. This study was undertaken to compare the changes of pancreatic enzyme secretion produced by CGRP and by stimulation or destruction of sensory nerves. Methods To stimulate sensory nerves, low doses of capsaicin (0.25–0.5 mg/kg) were given intraduodenally to the conscious rats with chronic pancreatic fistula. To inactivate sensory nerves high doses of capsaicin (100 mg/kg) were given subcutaneously 10 d before tests. For the in vitro experiments pancreatic slices and isolated pancreatic acini were prepared from intact and capsaicin-denervated rats. Results In conscious rats, CGRP given subcutaneously (5–10 μg/kg) and low doses of capsaicin given intraduodenally reduced basal pancreatic secretion. In isolated pancreatic acini, CGRP (10⁻¹⁰–10⁻⁶ M), but not capsaicin, increased basal or secretagog-stimulated amylase release. In pancreatic slices (containing nerve fibers) capsaicin (10⁻¹⁰–10⁻⁶ M) increased enzyme secretion, and this secretion was abolished by previous inactivation of sensory nerves by this neurotoxin. Capsaicin deactivation did not affect the secretory response of pancreatic acini to CGRP, cerulein, or urecholine. Sensory denervation by capsaicin did not change basal protein secretion, but reduced that produced by feeding or diversion of pancreatic juice to the exterior during first 2 h of the tests.     

Effect of diltiazem on left ventricular mass and diastolic filling in mild to moderate hypertension

It is still uncertain whether antihypertensive therapy with calcium antagonists in general, and diltiazem in particular, can reduce left ventricular (LV) mass index and improve LV diastolic filling in hypertension. Therefore, 24 patients with mild to moderate hypertension (diastolic blood pressure 95 to 114 mm Hg before therapy) were randomly assigned to receive either a sustained-release preparation of diltiazem (n = 13) or placebo (n = 11) for 16 weeks in a double-blind, parallel-group protocol. M-mode and pulsed Doppler echocardiograms were performed at baseline and at the end of monotherapy. Echocardiograms were read blindly by 2 independent observers. The patients who received placebo exhibited no change in blood pressure, cardiac dimensions or LV function. Diltiazem significantly reduced both systolic pressure (151 +/- 14 to 139 +/- 12 mm Hg) and diastolic pressure (101 +/- 4 to 90 +/- 7 mm Hg, both p less than 0.05). Posterior wall and septal wall thicknesses decreased, but the changes were not statistically significant. End-diastolic dimension was reduced by diltiazem from 53 +/- 5 to 51 +/- 5 mm (p less than 0.05). LV mass index decreased significantly with diltiazem by 10%, from 125 +/- 21 to 113 +/- 23 g/m2 (p less than 0.05). The LV wall thickness to radius ratio remained unchanged during both diltiazem and placebo treatments. Changes in LV mass index and blood pressure did not correlate, suggesting that this response is influenced by factors other than pressure reduction alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventricular arrhythmias during ergonovine-induced episodes of variant angina

Of 95 consecutive patients with active variant angina who underwent ergonovine testing in the coronary care unit while off treatment, 24 (25%) developed serious ventricular arrhythmias: ventricular tachycardia in eight, bigeminy in seven, pairs in five, and frequent ventricular extrasystoles in four. Ergonovine-induced arrhythmias were observed more often in patients with anterior than inferior ST segment elevation (p less than 0.05). ST segment elevation was significantly higher (10.3 +/- 8.1 vs 3.1 +/- 2.1 mm) in patients who developed arrhythmias. All ventricular arrhythmias began within 3 minutes after the onset of ST segment elevation. The intravenous administration of nitroglycerin eliminated arrhythmias in 22 of 24 cases; in only two patients did ventricular arrhythmias develop after the administration of nitroglycerin. Serious ventricular arrhythmias were found during spontaneous variant angina attacks in 14 of 24 patients with ergonovine-induced arrhythmias compared to 16 of 71 patients without ergonovine-induced arrhythmias (p less than 0.001). We conclude that arrhythmias during ergonovine testing are most often caused by ischemia and not reperfusion. Patients with arrhythmias during ergonovine-induced attacks are more likely to have arrhythmias during spontaneous attacks.     

Diagnostic accuracy of exercise thallium-201 scintigraphy in men with asymptomatic essential hypertension.

Coronary artery disease is responsible for much of the morbidity and mortality in patients with essential hypertension, and these complications have proven to be relatively resistant to antihypertensive therapy. However, the diagnosis of coronary disease in the hypertensive population has been considered problematic. In the present study, 30 asymptomatic patients with mild to moderate hypertension with positive exercise electrocardiograms (ECG) or stress thallium-201 scintigrams underwent coronary angiography to determine the accuracy of these tests for coronary artery disease. The exercise ECG was positive in 25 subjects, of whom 15 had significant coronary lesions and 10 did not. Thallium-201 scintigraphy proved more accurate: 17 of 18 patients with reversible abnormalities had significant obstructive coronary disease anatomically corresponding to the defect, one patient with a fixed defect had normal coronary arteries and was found to have an idiopathic cardiomyopathy, and 9 of 11 without defects had no significant lesions. The results were similar in populations with and without echocardiographic criteria for left ventricular hypertrophy. These findings indicate that despite previous suggestions to the contrary, thallium-201 scintigraphy can accurately diagnose coronary artery disease in most patients with asymptomatic essential hypertension, and that most asymptomatic hypertensive patients with physiologic evidence of myocardial ischemia have associated coronary artery disease.     

Cardiometabolic Changes and Disparities Among Persons With Spinal Cord Injury: A 17-Year Cohort Study

Background:

Cardiometabolic syndrome in individuals who are aging with spinal cord injury (SCI) increases the risk of cardiovascular disease and diabetes. Longitudinal research is needed on the natural progression of cardiometabolic syndrome in SCI.

Objective:

To identify the magnitude of changes in biomarkers of cardiometabolic syndrome and diabetes over time in people aging with SCI, and to discern how these biomarkers relate to demographics of race/ethnicity and sex.

Methods:

This cohort study was a follow-up of a convenience sample of 150 participants (mean age, 51.3; duration of SCI, 27.3 years) from a full cohort of 845 who participated in research in which physiologic and serologic data on cardiovascular disease had been prospectively collected (1993–1997). Inclusion criteria were adults with traumatic-onset SCI. Average years to follow-up were 15.7 ± 0.9. Assessments were age, race, level and completeness of injury, duration of injury, blood pressure, body mass index, waist circumference, serum lipids, fasting glucose, hemoglobin A1c, and medications used. Primary outcome was meeting at least 3 of the criteria for cardiometabolic syndrome.

Results:

The frequency of cardiometabolic syndrome increased significantly from 6.7% to 20.8% or 38.2% according to 2 definitions. It was significantly higher in Hispanics and apparently higher in women. Diabetes increased significantly by a factor of 6.7.

Conclusion:

Our data indicate clinically important increases in the frequency of cardiometabolic syndrome, especially among Hispanic and female participants, and a similar increase in diabetes among individuals aging with SCI. Clinical practice guidelines need to be customized for women and Hispanics with SCI.Key words: aging, cardiovascular disease, diabetes, dyslipidemia, metabolic syndrome, risk factorsCardiometabolic syndrome comprises a set of interrelated risk factors for cardiovascular disease and diabetes.^1,2 These risks are an escalating problem for people with spinal cord injury (SCI).^3–10 The main causes of cardiometabolic syndrome in persons with SCI are diet and fitness level.9 Overfeeding during initial rehabilitation can become habitual, and the effect is amplified by a lowered metabolic rate and muscle atrophy.⁹ The resulting weight gain and metabolic changes are difficult to reverse by exercise alone.11 The SCI population is aging. Consequently, cardiometabolic syndrome in people who are aging with SCI presents substantial challenges.The risk of cardiometabolic syndrome in SCI in the United States is as high as 58% for those who are relatively young, predominantly nonsmoking, and with intact adrenergic systems.¹² The prevalence of cardiometabolic syndrome is 34% in individuals with SCI in the United States,¹² with low high-density lipoprotein (HDL) cholesterol in 76%, high triglycerides in 68%, and hypertension in 29% of patients studied.¹² The National Cholesterol Education Project’s Adult Treatment Panel III Guidelines provide a 4-step sequential algorithm for customized management of dyslipidemia and cardiovascular disease.¹³ Lipid-lowering interventions were indicated in 63% of SCI patients studied, yet at the time of the study none of the patients had received such intervention.¹² Consequently, new evidence-based clinical practice guidelines are in development.¹⁴ Guidelines for the prevention and treatment of cardiometabolic syndrome must take into account both the natural progression of the syndrome and disparities in underserved and disadvantaged populations. Gaps in existing research suggest a need for longitudinal studies that characterize the natural progression of cardiometabolic syndrome in the SCI population and that assess the risk factors associated with its progression in disparate demographic groups. In the able-bodied, disparities associated with race/ethnicity include higher rates of coronary artery disease and/or diabetes among Blacks, Hispanics, and Asians/Pacific Islanders.^15–17 Cardiometabolic disparities associated with race/ ethnicity are probably related to nutrition that is linked to culture, which may be influenced by socioeconomic status, and to genetic adaptations coupled with cultural nutritional history. Racial/ ethnic cardiometabolic disparities may also be influenced by restricted access to health care associated with poverty. Cardiometabolic disparities related to sex are primarily influenced by ignorance in medical practice,^18–21 because screening, diagnostics, treatment, and research have been primarily focused on men.Our purpose was to characterize the natural progression of cardiometabolic disease in persons aging with SCI. The 2 objectives were to identify the magnitude of changes in cardiometabolic syndrome and overt diabetes status over 17 years in a cohort of 150 outpatients with chronic SCI, and to identify how these changes relate to demographics of race/ethnicity and sex.     

Ergonovine testing to detect spontaneous remissions of variant angina during long-term treatment with calcium antagonist drugs

A subgroup of 22 patients with variant angina who had responded well to calcium antagonist drugs were studied to determine if ergonovine testing could help assess the need for continued therapy. Before treatment all 22 patients exhibited angina with S-T elevation during ergonovine testing done in the coronary care unit according to a previously described protocol with sequential ergonovine doses of 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4 mg administered at 5 minute intervals. After 9.4 ± 4.7 (range 1 to 24) months of treatment (nifedipine 7 patients, diltiazem 3, verapamil 8, perhexiline 3, nifedipine and diltiazem 1), all patients were free from anginal attacks. Medication was discontinued and ergonovine testing repeated 24 to 48 hours later (3 weeks for perhexiline). In 12 of the 22 patiénts, angina or S-T segment shifts did not occur during the second ergonovine test to a maximal dose of 0.4 mg. Treatment was not restarted in these patients and all 12 remain free of variant anginal attacks 4.2 ± 2.9 (range 1 to 13) months later. In seven patients angina and S-T elevation occurred during the second ergonovine test, in the same electrocardiographic leads as during the test before treatment. In three patients the ergonovine test induced angina with S-T depression in the leads where S-T elevation had occurred during the previous test. Treatment was reinstituted in these 10 patients with a positive test. No complications resulted from ergonovine testing in any patient.We conclude that in many patients with variant angina, symptoms will disappear spontaneously and the ergonovine test will revert to negative. Treatment with calcium antagonist drugs can probably be safely discontinued in some patients with variant angina; ergonovine testing appears to be helpful in identifying such patients. Longer periods of follow-up are required to confirm that symptoms do not recur.     

Air pollution and daily hospital admissions in metropolitan Los Angeles

We used daily time-series analysis to evaluate associations between ambient carbon monoxide, nitrogen dioxide, particulate matter [less than and equal to] 10 microm in aerodynamic diameter (PM(10)), or ozone concentrations, and hospital admissions for cardiopulmonary illnesses in metropolitan Los Angeles during 1992-1995. We performed Poisson regressions for the entire patient population and for subgroups defined by season, region, or personal characteristics, allowing for effects of temporal variation, weather, and autocorrelation. CO showed the most consistently significant (p<0.05) relationships to cardiovascular admissions. A wintertime 25th-75th percentile increase in CO (1.1-2.2 ppm) predicted an increase of 4% in cardiovascular admissions. NO(2), and, to a lesser extent, PM(10) tracked CO and showed similar associations with cardiovascular disease, but O(3) was negatively or nonsignificantly associated. No significant demographic differences were found, although increased cardiovascular effects were suggested in diabetics, in whites and blacks (relative to Hispanics and Asians), and in persons older than 65 years of age. Pulmonary disease admissions associated more with NO(2) and PM(10) than with CO. Pulmonary effects were generally smaller than cardiovascular effects and were more sensitive to the choice of model. We conclude that in Los Angeles, atmospheric stagnation with high primary (CO/NO(2)/PM(10)) pollution, most common in autumn/winter, increases the risk of hospitalization for cardiopulmonary illness. Summer photochemical pollution (high O(3)) apparently presents less risk.