Preventing progression of coronary atherosclerosis: beyond cholesterol lowering.
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Cholesterol↗
Biomedical subjects
D Waters
Publications and source records attributed to D Waters.
Dipyridamole-thallium imaging: minimum dose requirements.
A total of 372 consecutive dipyridamole-thallium studies were reviewed to determine if a relationship existed between the dose of dipyridamole administered and the likelihood that thallium images would show reversible defects. Men who received a dose of less than 31 mg were less likely to have thallium redistribution (P = 0.0001). Until the ideal study involving repeat testing with incremental dipyridamole doses on different days is carried out, the authors recommend that a minimal dose of 31 mg be administered for dipyridamole-thallium imaging.
Coronary Vessels↗
Unstable angina: special considerations in the postbypass patient.
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Angina, Unstable↗
Angioplasty of bypass grafts and native arteries.
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Angioplasty, Balloon, Coronary↗
Transient left ventricular cavitary dilation during dipyridamole-thallium imaging as an indicator of severe coronary artery disease.
Transient left ventricular (LV) cavitary dilation during dipyridamole-thallium imaging was reported in 45 of 510 (9%) consecutive patients referred for dipyridamole-thallium imaging. Clinical and hemodynamic effects observed during dipyridamole infusion were not predictive of transient cavitary dilation on the thallium images. Coronary angiography was performed in 32 of the 45 patients: 75% had either left main, 3-vessel or "high-risk" 2-vessel coronary artery disease. Although 25 of 45 patients (56%) with transient cavitary dilation were either asymptomatic or had only grade 1/4 effort angina, 16 of 25 patients (64%) not referred for coronary revascularization sustained a cardiac event during a mean follow-up of 12 months. Most events were cardiac deaths (75%) and 87% of events occurred within 4 months of the test. Noncardiac surgery was performed in 187 of the 510 patients. The postoperative cardiac event rate was 2% in the 101 patients with normal scans or fixed defects, 19% in 75 patients with reversible perfusion defects and 58% in 12 patients with reversible cavitary dilation (p less than 0.0001). Thus, transient LV dilation during dipyridamole-thallium imaging is a marker of severe underlying coronary artery disease, denotes a poor prognosis and predicts a high risk of postoperative cardiac complications in patients who undergo noncardiac surgery.
Coronary Angiography↗
Effects of nitroglycerin at therapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction.
The platelet aggregation response to adenosine diphosphate (ADP) and to thrombin was quantified in 10 patients, 5 with unstable angina pectoris and 5 with acute myocardial infarction, before, during and after a 45-minute infusion of nitroglycerin. An impedance aggregometer allowing rapid bedside studies in whole blood was used. The reproducibility of the methods was documented to be within 10%. Doses of nitroglycerin were titrated for a 10 mm Hg decrease in mean arterial blood pressure with mean doses being 1.2 +/- 0.2 (standard error of the mean) micrograms/kg/min. Nitroglycerin decreased the area under the aggregation curve induced by ADP from 43 +/- 3.6 to 30 +/- 6.3 cm2 (p = 0.007) and by thrombin from 8.9 +/- 1.7 to 4.1 +/- 0.9 cm2 (p = 0.003). Peak responses to ADP were decreased from 13.3 +/- 1 to 9.1 +/- 1.7 ohms (p = 0.005) and to thrombin from 9.3 +/- 2 to 5.0 +/- 1.2 ohms (p = 0.003). All patients had greater than or equal to 50% inhibition with 1 agent or the other and the inhibition was greater than 50% with each of the 2 aggregating agents in 6 patients. Analyses performed on blood withdrawn 15 minutes after the discontinuation of nitroglycerin showed a return to baseline before nitroglycerin results. When analyses were delayed and performed on blood preserved at room temperature for 30 minutes, no effect of nitroglycerin could be detected. Thus, bedside platelet aggregation studies document a significant and reversible effect of nitroglycerin at therapeutic doses on platelet function.
Adenosine Diphosphate↗
What is an antiarrhythmic drug? From clinical trials to fundamental concepts.
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Animals↗
Hemodynamic, platelet and clinical responses to prostacyclin in unstable angina pectoris.
The hemodynamic and platelet effects of prostacyclin (PGI2) were investigated in 27 patients with unstable angina (14 treated patients; 13 control subjects) given a 72-hour infusion (5 ng/kg/min) or placebo. This randomized study was double-blind and conducted as a substudy of a multicenter trial testing the clinical efficacy of PGI2. The clinical and angiographic features were identical in the 2 groups. Blood pressure and heart rate were not modified significantly by PGI2. A recurrence of angina during infusion occurred in 8 treated patients (57.1%) and in 8 control subjects (61.5%). Two patients receiving PGI2 and none in the control group developed a myocardial infarction. Levels of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2, increased from baseline values (less than 20 pg/ml) to 605 +/- 41 pg/ml during infusion. Levels of fibrinopeptide A, beta-thromboglobulin, platelet factor 4, thromboxane B2 and the platelet aggregates ratio in blood were similar between the 2 groups before, during and after PGI2 infusion. Prostacyclin reduced ex vivo platelet aggregation to adenosine diphosphate and thromboxane B2 generation by approximately 50% during the infusion period with return of aggregation to baseline and platelet thromboxane B2 production to above baseline after the discontinuation of PGI2. Thus, despite favorable effects of PGI2 upon platelet aggregation and systemic hemodynamics, the prostanoid failed to improve the clinical evolution of unstable angina.
6-Ketoprostaglandin F1 alpha↗
Is dipyridamole-thallium imaging preferable to submaximal exercise thallium testing for risk stratification after thrombolysis?
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Aged↗
Postoperative myocardial infarction and cardiac death. Predictive value of dipyridamole-thallium imaging and five clinical scoring systems based on multifactorial analysis.
Sixty-six patients unable to complete a standard preoperative exercise test because of physical limitations were studied to determine the predictive value of individual clinical parameters, of clinical scoring systems based on multifactorial analysis, and of dipyridamole-thallium imaging before major general and vascular surgery. Study endpoints were limited to postoperative myocardial infarction or cardiac death before hospital discharge. There were nine postoperative cardiac events (seven deaths and two nonfatal infarctions). There was no statistical correlation between cardiac events and preoperative clinical descriptors, including individual clinical parameters, the Dripps-American Surgical Association score, the Goldman Cardiac Risk Index score, the Detsky Modified Cardiac Risk Index score, Eagle's clinical markers of low surgical risk, and the probability of postoperative events as determined by Cooperman's equation. There were no cardiac events in 30 patients with normal dipyridamole-thallium scans or in nine patients with fixed myocardial perfusion defects. Of 21 patients with reversible perfusion defects who underwent surgery, nine had a postoperative cardiac event (sensitivity, 100%; specificity, 43%). In the six other patients with reversible defects, preoperative angiography showed severe coronary disease or cardiomyopathy. Thus in patients unable to complete a standard exercise stress test, postoperative outcome cannot be predicted clinically before major general and vascular surgery, whereas dipyridamole-thallium imaging successfully identified all patients who sustained a postoperative cardiac event.
Aged↗
Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees.
Emergence in two chimpanzees of human immunodeficiency virus type 1 (HIV-1) IIIB variants resistant to neutralization by the preexisting antibody is described. Viruses isolated from the HIV-1 IIIB gp120-vaccinated and -challenged animal were more resistant to neutralization by the chimpanzee's own serum than viruses isolated from the naive infected animal, indicating immune pressure as the selective mechanism. However, all reisolated viruses were 16- to 256-fold more neutralization resistant than the inoculum virus to antibodies binding to the third variable domain (V3) of the HIV-1 external envelope. Early chimpanzee serum samples that neutralized the inoculum strain but not the reisolated viruses were found to bind an HIV-1 IIIB common nonapeptide (IQRGPGRAF) derived from the gp120 isolate-specific V3 domain shown to induce isolate-specific neutralization in other animals. Amplification of the V3 coding sequence by polymerase chain reaction and subsequent sequence analysis of the neutralization-resistant variants obtained from in vivo-infected animals indicated that early resistance to neutralization by an HIV-1 IIIB monoclonal antibody (0.5 beta) was conferred by changes outside the direct binding site for the selective neutralizing antibody. The reisolated neutralization-resistant isolates consisted of the lower-replication-competent virus subpopulations of the HIV-1 IIIB stock, as confirmed by biological and sequence analyses. In vitro passage of the HIV-1 IIIB stock through chimpanzee and human peripheral blood mononuclear cell cultures void of HIV-specific antibody resulted in homogenic amplification of the more-replication-competent subpopulation preexisting in the original viral stock, suggesting a role for the immune system in suppressing the more-replication-competent viruses.
Acquired Immunodeficiency Syndrome↗
Left-to-right atrial shunting after percutaneous mitral valvuloplasty. Incidence and long-term hemodynamic follow-up.
To assess the incidence and long-term evolution of left-to-right atrial shunting (AS) after the performance of percutaneous mitral valvuloplasty (PMV), venovenous indicator dilution curves and right heart oximetric measurements were obtained in 68 consecutive patients before and after successful PMV. The procedure increased the mitral valve area (p less than 0.0001) and decreased the mitral gradient (p less than 0.0001). No AS was detected before PMV, but it was detected immediately after PMV. Oximetry identified AS in 17 patients (25%), and dilution curves identified AS in an additional 25 (total, 62%). The ratio of mean pulmonary to systemic blood flow (Qp/Qs) was 1.31 +/- 0.2, and in six patients (9%), the ratio was 1.5 or greater. Among nine clinical, 20 hemodynamic, and six procedural variables, stepwise logistic regression analysis selected the following as independent predictors of AS: smaller increases in valve area (p = 0.01) after PMV, absence of previous surgical commissurotomy (p = 0.02), mitral valve calcification (p = 0.02), and smaller left atria (p = 0.06). Among the 33 patients recatheterized at 6 months, oximetry had detected AS in 10, and dilution curves detected AS in an additional nine (total, 58%) immediately after PMV. At 6 months, AS had decreased or disappeared in 14 of these patients (74%), had increased in three (16%), and was unchanged in two (10%). Overall, at 6 months, oximetry identified AS in three patients, and dilution curves identified AS in an additional 13 (total, 48%). AS was detected at 6 months in only three patients but was not detected immediately after PMV. Although AS is very frequent immediately after PMV, Qp/Qs is usually less than 1.5. The appearance of shunting correlates with patient characteristics and with less improvement in valve area after PMV. Atrial shunting usually persists at 6 months, but its severity almost always decreases.
Blood Circulation↗
A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis.
To determine whether calcium channel blockers influence the progression of coronary atherosclerosis, 383 patients age 65 years or less with 5-75% stenoses in at least four coronary artery segments were selected at random within 1 month of coronary arteriography to participate in double-blind therapy with a placebo or nicardipine 30 mg three times daily. Coronary events (5 deaths, 22 myocardial infarctions, and 28 unstable anginas) occurred in 28 of 192 nicardipine patients and 23 of 191 placebo patients (p = NS). At 24 months coronary arteriography was repeated in 335 patients. Progression, defined as a 10% or more worsening in diameter stenosis, measured quantitatively, was found in 147 of 1,153 lesions (12.7%) in 168 nicardipine patients and in 170 of 1,170 lesions (14.5%) in 167 placebo patients (p = NS). Ninety-two nicardipine patients (55%) and 95 placebo patients (57%) had progression at one or more sites (p = NS). Regression, that is, an improvement by 10% or more in diameter stenosis, was seen in 140 of 2,323 lesions (6.0%) overall, with no significant intergroup difference. Among the 217 patients with 411 stenoses of 20% or less in the first study, such minimal lesions progressed in only 15 of 99 nicardipine patients compared with 32 of 118 placebo patients (15% versus 27%, p = 0.046). In this subgroup, 16 of 178 minimal lesions in nicardipine patients and 38 of 233 minimal lesions in placebo patients progressed (p = 0.038). By stepwise logistic-regression analysis, baseline systolic blood pressure (p = 0.04) and the change in systolic blood pressure between baseline and 6 months (p = 0.002) correlated with progression of minimal lesions. This suggested blood pressure reduction may account for the beneficial action of nicardipine. These results suggested nicardipine has no effect on advanced coronary atherosclerosis but may retard the progression of minimal lesions.
Adult↗
Superiority of dipyridamole over exercise testing when exercise thallium imaging is limited by angina.
The extent of jeopardized myocardium can be underestimated on stress thallium myocardial perfusion images when exercise tolerance is limited by angina pectoris. A patient's tolerance for pain can influence the degree of myocardial ischemia observed on myocardial perfusion images during effort angina. A case is reported of a patient with angina pectoris showing mild ischemia limited to one myocardial segment on exercise thallium images, but severe and extensive reversible perfusion defects during dipyridamole-thallium imaging, and a 70% stenosis of the left main coronary artery on coronary angiography.
Angina Pectoris↗
Evidence for rapid selection and deletion of HIV-1 subpopulations in vivo by V3-specific neutralizing antibody: a model of humoral-associated selection.
Emergence in two chimpanzees of HIV-1 HTLV-IIIB variants resistant to neutralization by the pre-existing antibody is described. Viruses isolated from the HTLV-IIIB gp120 vaccinated and challenged animal were more resistant to neutralization, had more heterogenic genomes and showed more pronounced antigenic drift as determined by serotypic neutralization analysis than viruses isolated from the naive infected animal, indicating immune pressure as the selective mechanism. The earliest selecting antibody population detected in the chimpanzees appeared to be conformationally dependent. This was demonstrated by its ability to neutralize only the most replication-competent sub-populations of the HTLV-IIIB inoculum strain, yet was found to bind a HTLV-IIIB common nonapeptide (IQRGPGRAF) derived from the gp120 isolate-specific 3rd variable domain (V3) also known to induce isolate-specific neutralization in multiple species. Each of the recovered isolates had become resistant to neutralization by both a monoclonal (0.5 beta) and polyclonal HTLV-IIIB gp120 V3-specific antibody by as much as 16 to 256-fold. Amplification of the V3 coding sequence by polymerase chain reaction and subsequent sequence analysis of the neutralization-resistant variants obtained from in vivo infected animals indicated that resistance to neutralization was conferred by changes outside the direct binding site for the selective neutralizing antibody. Further studies indicated that apparent neutralization-resistant variants, yielded after in vitro passage through chimpanzee and human peripheral blood mononuclear cell cultures void of HIV-specific antibody, result from the homogenic amplification of the more replication competent sub-population pre-existing in the original viral stock. These faster replicating sub-populations appear to dominate initially and therefore are the initial prime targets recognized by the chimpanzee humoral immune system upon infection in vivo and thus eliminated. The described finding of virus escape due to a conformationally-induced flexibility of the major neutralization epitope termed "conformational-V3 hypervariability", coupled to the known primary amino acid hypervariability of this epitope (V3) termed "linear-V3 hypervariability", may be all that is required by the virus to survive in an otherwise effective humoral immune system.
Amino Acid Sequence↗
Sexual transmission of human T-lymphotropic virus type I (HTLV-I).
STUDY OBJECTIVE: To study the seroprevalence of human T-lymphotropic virus type I (HTLV-I) in a sexually active population and to determine sexual behavior risk factors for infection. DESIGN: Cross-sectional seroprevalence study using enzyme-linked immunosorbent assay (ELISA) and Western blot. Risk-factor data were gathered by administered questionnaire and chart review. SETTING: Two urban, primary care clinics for persons with sexually transmitted diseases run by the Jamaican Ministry of Health. PATIENTS: Of the 2050 consecutive patients presenting with new episodes of sexually transmitted disease, 1977 patients were eligible for analysis. MEASUREMENTS AND RESULTS: Overall HTLV-I seroprevalence was 5.7%; prevalence increased with age from 1.6% (age, 14 to 19 years) to 5.1% (age, 30 years and older) in men and from 5.3% (age, 14 to 19 years) to 14.1% (age, 30 years and older) in women. Compared with a reference cohort of food service employees, age-adjusted HTLV-I seroprevalence was increased in female patients with sexually transmitted disease (odds ratio = 1.83; CI, 1.41 to 2.83) but not in male patients with sexually transmitted disease. Independent risk factors for HTLV-I infection in women included having had more than ten lifetime sexual partners (odds ratio = 3.52, CI, 1.28 to 9.69) and a current diagnosis of syphilis (odds ratio = 2.12; CI, 1.12 to 3.99). In men, a history of penile sores or ulcers (odds ratio = 2.13; CI, 1.05 to 4.33) and a current diagnosis of syphilis (odds ratio = 3.56; CI, 1.24 to 10.22) were independent risk factors for HTLV-I infection. Of 1977 patients, 5 (0.3%) had antibodies to human immunodeficiency virus type 1 (HIV-1), including 2 with HTLV-I and HIV-1 coinfection. CONCLUSIONS: We conclude that HTLV-I is transmitted from infected men to women during sexual intercourse. Our data are consistent with the lower efficiency of female-to-male sexual transmission of HTLV-I, but penile ulcers or concurrent syphilis may increase a man's risk of infection.
Adolescent↗
Comparison by quantitative angiographic assessment of coronary stenoses of one view showing the severest narrowing to two orthogonal views.
Quantitative coronary arteriographic measurements were compared in 2 orthogonal views with the view that clearly showed the stenosis at its most severe in 147 lesions from 147 patients before, immediately after and 6 months after PTCA. In 21 of 147 patients (14%), 2 views could not be measured for technical reasons, even though all angiographers had tried to film 2 views. Lesion severity was slightly worse for 1 compared with 2 views (3.3 +/- 3.3% before PTCA, 3.6 +/- 3.8% after PTCA and 3.1 +/- 3.8% at follow-up). Similarly, minimal diameter was less for 1 view (0.11 +/- 0.09 mm before PTCA, 0.15 +/- 0.12 mm after PTCA and 0.13 +/- 0.09 mm at 6 months). When this systematic difference was taken into account, the 2 methods were within +/- 0.1 mm for minimal diameter in 288 of 376 measurements (77%) and within +/- 0.2 mm in 96%. For percent diameter stenosis the 2 methods were within +/- 5% in 90% and within +/- 10% in all but 2.7% (10 of 376). Thus, for routine clinical assessment, measurement of 1 view is adequate; for research purposes orthogonal views may sometimes be required.
Angiography↗
Usefulness of the severity and extent of reversible perfusion defects during thallium-dipyridamole imaging for cardiac risk assessment before noncardiac surgery.
Thallium-dipyridamole imaging is a very sensitive test for predicting cardiac events after noncardiac surgery, but it lacks specificity. To improve specificity, a semiquantitative scoring system was developed that combined dipyridamole-induced reversible left ventricular dilatation with scintigraphic indexes for severity and extent of reversible perfusion defects. Using this scoring system, patients were classified into low, intermediate and high risk subgroups. Thallium-dipyridamole imaging was performed in 66 patients before major general and vascular surgery. Thirty-nine patients classified as low risk (30 with normal scans and 9 with fixed defects) underwent surgery uneventfully. Surgery was cancelled in 6 patients with extensive thallium redistribution and coronary angiography was performed because of severe coronary artery disease in 5 and idiopathic dilated cardiomyopathy in 1. In the remaining 21 patients with thallium redistribution, a positive statistical correlation (p = 0.001) between scintigraphic indexes of severity and extent, and cardiac events was noted. Using cutoff values for the scintigraphic indexes, patients with reversible defects could be classified into intermediate and high risk subgroups. Only 1 of 11 patients at intermediate risk developed a complication, whereas 8 of 10 patients at high risk had a postoperative event (7 deaths and 1 myocardial infarction). Thus, using scintigraphic indexes for severity and extent, patients with reversible defects can be stratified into an intermediate risk subgroup that can safely undergo surgery and a high risk subgroup that requires coronary angiography.
Angiography↗