Differential plasma endothelin levels in subgroups of patients with angina and angiographically normal coronary arteries. Coronary Artery Disease Research Group

To obtain a comprehensive overview of chromosomal alterations that may underlie human papillomavirus (HPV)-mediated immortalization, 4 foreskin keratinocyte cell lines generated by transfection with either HPV 16 (cell lines FK16A and FK16B) or HPV 18 (FK18A and FK18B) were subjected to chromosomal analysis using comparative genomic hybridization (CGH). Three cell lines were analyzed both in the mortal state during their extended lifespan and in the subsequent immortal state. From cell line FK18A, only immortal cells were tested. Chromosomal imbalances increased in number through the process of immortalization. Subsequent loss of heterozygosity (LOH) analysis, using a panel of 21 microsatellite markers selected on the basis of CGH losses, revealed no clonal LOHs in cells at the mortal stage. However, in the immortal descendants 67% of underrepresentations detected by CGH were expressed as clonal LOH at the respective loci. Clonal LOHs at 3p, 11p and 13q were detected in 2 cell lines each and were thus considered non-random. Immortal cells of 1 cell line (FK18B) revealed LOH at all 3 loci. Moreover, all immortal cell lines displaying allelic losses at one or more of these loci shared a severely dysplastic phenotype after organotypic culturing, as shown previously. Therefore, loss-of-function mutations of genes at these loci, eventually in combination, are potentially involved in the process of HPV-mediated immortalization that is attended by a loss of terminal differentiation. Since chromosomal changes at these loci are also found in HPV-associated carcinomas in vivo, the HPV-transfected cell lines seem to provide a valuable model system for studying HPV-mediated carcinogenesis.     

Early management of unstable coronary artery disease. Coronary angiography is the first measure in high-risk patients

Unstable coronary artery disease is currently the major cause of admissions to coronary intensive care units, accounting for 30-40 per cent of cases. The underlying cause is rupture of an atherosclerotic plaque, coronary blood flow being impeded by a superimposed thrombus. New and more effective antithrombotic drugs are becoming increasingly available. Simultaneous early coronary angioplasty, stenting or bypass surgery provide the most effective amelioration of symptoms. Early revascularisation has not hitherto been found to reduce the risk of myocardial infarction or mortality in patients without signs of severe ischaemia. In this large category of cardiac patients, treatment strategy selection is of considerable importance to the effective utilisation of resources.     

Prognostic significance of cerebrovascular disease in 11,526 chronic coronary artery disease patients. Bezafibrate Infarction Prevention (BIP) Study Group

Patients with chronic CAD and a history of cerebrovascular events were compared with patients without prior cerebrovascular events to assess the effect of these events on 5-year prognosis. Despite adjustment for older age and higher comorbidity among patients who had experienced a cerebrovascular event, a history of such an event was associated with an increased risk of 1.86 for total mortality.     

Effect of pravastatin (10 mg/day) on progression of coronary atherosclerosis in patients with serum total cholesterol levels from 160 to 220 mg/dl and angiographically documented coronary artery disease. Coronary Artery Regression Study (CARS) Group

To evaluate the effect of pravastatin on progression of coronary atherosclerosis in normocholesterolemic patients with coronary artery disease (CAD), 90 patients with CAD and serum cholesterol levels of 160 to 220 mg/dl were randomized into a pravastatin (10 mg/day) group (n = 45) and control group (n = 45) in a 2-year study. The proportions of patients with progression (an increase of > or = 15% in percent stenosis) and regression (a decrease of > or = 15% in percent stenosis) of coronary atherosclerosis were compared between the 2 groups. Of 90 patients, 80 (89%) had a final angiogram: the pravastatin (n = 39) and control group (n = 41). Percent changes in total cholesterol, low-density lipoprotein cholesterol, and apoprotein B levels were significantly greater in the pravastatin group than in the control group (total cholesterol -11 +/- 12% vs 3 +/- 15%, p < 0.01; low-density lipoprotein cholesterol -18 +/- 16% vs 4 +/- 21%, p < 0.01; apoprotein B -5 +/- 20% vs 6 +/- 20%, p < 0.05). The proportion of patients with progression of coronary atherosclerosis was significantly smaller in the pravastatin group than in the control group (21% vs 49%, p < 0.05). The proportion of patients with disease regression did not differ in the 2 groups (3% vs 2%, p = NS). In conclusion, this study indicates that cholesterol-lowering therapy with pravastatin can prevent the progression of coronary atherosclerosis even in normocholesterolemic patients with established CAD.     

Social relations and extent and severity of coronary artery disease. The Stockholm Female Coronary Risk Study

Peak bone mass is a major determinant of risk of osteoporotic fracture. Family and twin studies have found a strong genetic component to the determination of bone mineral density (BMD). However, BMD is a complex trait whose expression is confounded by environmental influences and polygenic inheritance. The number, locations, and effects of the individual genes contributing to natural variation in this trait are all unknown. Experimental animal models provide a means to circumvent complicating environmental factors, and the development of dense genetic maps based on molecular markers now provides opportunities to resolve quantitative genetic variation into individual regions of the genome influencing a given trait (quantitative trait loci, QTL). To begin to identify the heritable determinants of BMD, we have examined genetically distinct laboratory mouse strains raised under strict environmental control. Mouse whole-body bone mineral content by dual-energy X-ray absorptiometry (DXA) correlated strongly with skeletal calcium content by ashing, and peak whole-body BMD by DXA in female mice occurred at approximately 80-90 days of age. We therefore determined mean body weight and peak whole body BMD values in 12-week-old female mice from a panel of 24 recombinant inbred (RI) BXD strains, derived from a cross between C57BL/6 and DBA/2 progenitors. The distribution of body weight and BMD values among the strains clearly indicated the presence of strong genetic influences on both of these traits, with an estimated narrow sense heritability of 60% and 35%, respectively. The patterns of differences in body weight and peak whole body BMD in the BXD strains were then integrated with a large database of genetic markers previously defined in the RI BXD strains to generate chromosome map sites for QTL. After correction for redundancy among the significant correlations, QTL analysis of the BXD RI strain series provisionally identified 10 chromosomal sites linked to peak bone mass development in the female. Several of the identified sites map near genes encoding hormones, structural proteins, and cell surface receptors that are intricately involved in skeletal homeostasis. Four QTL for body weight were also identified. One of these loci was also strongly linked to inherited variation in BMD. This finding suggests that body weight and peak BMD may be influenced by linked genes or perhaps by common genes with pleiotropic effects. Our phenotyping in the RI BXD strains has allowed us to map a number of specific genetic loci strongly related to the acquisition of peak BMD. Confirmation of these findings will likely result in the understanding of which genes control skeletal health.     

Coronary artery disease in diabetic patients with lower-extremity arterial disease: disease characteristics and survival. A report from the Coronary Artery Surgery Study (CASS) registry

OBJECTIVE: Patients who have diabetes and lower-extremity arterial disease (LEAD) are at an increased risk of dying from coronary artery disease (CAD). This study was undertaken to: 1) define the clinical and arteriographic factors associated with LEAD among diabetic patients; 2) determine the long-term survival and predictors of mortality of diabetic patients with LEAD, compared to those without LEAD; and 3) determine if the presence of LEAD is an independent risk factor for mortality among diabetic patients with CAD. RESEARCH DESIGN AND METHODS: A total of 263 diabetic patients from the Coronary Artery Surgery Study (CASS) registry with LEAD, who were > or = 50 years of age, and who had arteriographically proven CAD, were identified and followed for a mean of 12.8 years. A total of 1,349 comparably aged diabetic patients from the CASS registry with CAD and no evidence of LEAD were followed for an equivalent period of time. RESULTS: Compared with diabetic patients without LEAD, diabetic patients with LEAD were characterized by the presence of cerebrovascular disease, a high rate of current smoking, elevated systolic blood pressure, high grades of angina pectoris, and digitalis use. Severity of epicardial CAD and extent of CAD were not independent predictors of the presence of LEAD. On follow-up, diabetic patients with LEAD had significantly higher mortality (mostly cardiovascular) than diabetic patients without LEAD, with a median survival of 8.1 and 10.9 years, respectively. On multivariate analysis, age, the number of significantly narrowed coronary arteries, and the presence of left ventricular dysfunction predicted mortality in both subsets of diabetic patients. Among all the diabetic patients with CAD, the presence of LEAD was an independent risk factor for mortality. CONCLUSIONS: Diabetic patients with LEAD have a higher mortality rate (mostly cardiovascular) than diabetic patients without LEAD, despite no apparent anatomic differences in the severity and extent of CAD. This suggests that factors associated with the presence of LEAD, other than the anatomy of the coronary circulation, may play a role in determining survival among diabetic patients with LEAD and CAD.     

A national study of postoperative mortality associated with coronary artery bypass grafting in Israel. ISCAB Consortium. Israel Coronary Artery Bypass Study

BACKGROUND: Investigation of observed differences in outcomes among medical centers is of major interest to the medical community and the public and has a substantial impact on efforts to improve the quality of medical care. METHODS: This study analyzed data from consecutive patients who underwent isolated coronary artery bypass grafting at 14 medical centers. Data included demographic and clinical information, comorbidity, cardiac catheterization results, and 30-day postoperative vitality status. Logistic regression analysis was used to identify variables associated with mortality. An outlier hospital was defined as one having an observed mortality outside the 95% confidence interval boundaries around the expected mortality rate calculated, given the patient risk factors. RESULTS: The overall crude 30-day mortality rate for isolated coronary artery bypass grafting among the 4,835 patients in this study was 3.1%. The rate varied among centers, ranging from 0.85% to 7.05%. Predictors of 30-day mortality included advanced age, female sex, diabetes mellitus, poor left ventricular function, high creatinine level, high priority of operation, and three-vessel disease (with or without left main coronary artery disease). After adjustment for risk factors, two hospitals were defined as outliers. CONCLUSIONS: The observed disparity in early mortality among patients undergoing coronary artery bypass grafting is not due solely to differences in case mix.     

Coronary collateral blood-flow velocity improves with repeated coronary occlusions during angioplasty in patients with coronary artery disease and systemic hypertension

The heterogeneity of schizophrenia has led to a multitude of diagnostic criteria systems. Thus, the best strategy for schizophrenia research might be the use of several diagnostic systems simultaneously. This polydiagnostic approach can be associated with isolating subtypes of symptoms or patients. In this way, the authors present several approaches such as, first, dimensional approaches, second, cluster analyses, and third the selection of a very homogeneous subtype with standardized criteria. One homogeneous subtype can be represented by deficit schizophrenia according to Carpenter as defined by the Schedule of Deficit Syndrome.     

Smoking cessation and severity of disease: The Coronary Artery Smoking Intervention Study.

Tested the effectiveness of an individually delivered behavioral multicomponent smoking intervention (SI) against offering advice only (AO) to 267 patients (aged 30–75 yrs) after coronary arteriography. After 6 mo, 51% of AO Ss and 62% of SI Ss reported abstinence. Validated rates were 34% and 45% for AO and SI Ss, respectively. At 6 mo, the SI had the most effect for Ss with more severe coronary artery disease (CAD) who had been admitted with a myocardial infarction even after controlling for baseline characteristics such as stage of readiness for change, sex, and self-efficacy. At 12 mo follow-up, only severity of disease mediated SI effects. Similar results were seen for cotinine-validated cessation. Data confirm the effectiveness of individually administered SI for more seriously ill patients with CAD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reexploration for hemorrhage following coronary artery bypass grafting: incidence and risk factors. Northern New England Cardiovascular Disease Study Group

Thorotrast, a 25% colloidal suspension of 232ThO2, was formerly used as a radiographic contrast medium. Although epidemiological studies have shown that alpha particles emitted from 232Th and its decay products incorporated in the bone marrow cause leukemia, the use of these data for alpha particle induced leukemogenesis risk estimation has been criticized mainly for inhomogeneity of Thorotrast distribution. Four monkeys were injected with Thorotrast to investigate the degree of inhomogeneity in the thorium content of different bone marrow sites and the cellular localization of Thorotrast. Two were injected via an artery and two via a vein and sacrificed either at 1 wk or 3 to 4 y after injection. Microscopic, solid state autoradiography and back scatter electron imaging methods were applied to several bone sites to determine the degree of inhomogeneity. Quantification was performed using x-ray fluorescence for trabecular bone and bone marrow and neutron activation analysis for compact bones. At 1 wk Thorotrast was found to be distributed evenly in the red marrow; by 3 and 4 y conglomerates were seen which were restricted to macrophages. The monkey was found to be a good model for humans. The choice of injection route did not noticeably affect the Thorotrast distribution in bones of the skeletal system. Considering the even distribution of Thorotrast within the red bone marrow at early times after its injection, the inevitable diffusion of thorium progeny from the particles, the mobility of bone marrow macrophages, and the well established correction factor of self-absorption within conglomerates, these results suggest that data derived from Thorotrast patients are useful for risk estimation of alpha particle induced leukemia.     

Prognostic value of pharmacological stress echocardiography in women with chest pain and unknown coronary artery disease

OBJECTIVES: In this study we sought to investigate the prognostic value of pharmacological stress echocardiography in women referred for chest pain, having unknown coronary artery disease. BACKGROUND: The noninvasive identification of a high-risk subgroup among women with chest pain and unknown coronary artery disease is an unresolved task to date. METHODS: A total of 456 women (mean [+/-SD] age 63+/-10 years) underwent pharmacological stress echocardiography with either dipyridamole (n = 305) or dobutamine (n = 151) for evaluation of chest pain and were followed-up for 32+/-19 months. None of them had a previous diagnosis of coronary artery disease. RESULTS: No major complication occurred during stress testing. Five tests (1.1%) were prematurely interrupted because of the appearance of side effects. Echocardiographic positivity was identified in 51 patients. During the follow-up, 23 cardiac events occurred: 3 deaths, 10 infarctions and 10 cases of unstable angina; an additional 21 patients underwent coronary revascularization. At Cox analysis, the echocardiographic evidence of ischemia was found as the only independent predictor of hard cardiac events (death, infarction) (odds ratio [OR] = 27.5; 95% confidence interval [CI] = (6.5 to 115.5; p = 0.0000). When spontaneous cardiac events (death, infarction and unstable angina) were considered as endpoints, the positive echocardiographic result (OR = 23.9; 95% CI = 8.6 to 66.8; p = 0.0000) and family history of coronary artery disease (OR = 3.7; 95% CI = 1.5 to 9.1; p = 0.0037) were independently correlated with prognosis. By using an interactive stepwise procedure, the prognostic value of stress echocardiography was found to be incremental to that provided by clinical variables, both considering hard and spontaneous cardiac events as endpoints. The 3-year survival rate for the negative and the positive population was respectively, 99.5% and 69.5% (p = 0.0000) considering hard cardiac events, 99.2% and 50.6% (p = 0.0000) considering spontaneous cardiac events. CONCLUSIONS: Pharmacological stress echocardiography is safe, highly feasible and effective in risk stratification of women with chest pain and unknown coronary artery disease, also when hard endpoints are considered. Its use can have relevant implications in daily clinical practice for selection of patients needing further investigations.     

Effects of aspirin treatment on survival in non-insulin-dependent diabetic patients with coronary artery disease. Israeli Bezafibrate Infarction Prevention Study Group

We studied seizures that occur during the acute phase of aseptic and bacterial meningitis in childhood. Of the 108 children with aseptic meningitis, five had seizures (4.7%). Four patients developed them within 24 hours of the onset of the initial symptom (fever in 3 cases), and three had repeated seizures on the first day. One case had SIADH complication, but another neurologic abnormalities were not observed. On the 18 children with bacterial meningitis, three cases (16.7%) had seizure, which occurred on the second day of illness. Disturbance of consciousness and cerebral hypertension were observed in 2 cases each, and abnormal cerebral CT findings in all the three. The NSE level in the cerebrospinal fluid was elevated in 2 cases. Thus, seizures occurring in the acute phase of aseptic meningitis may reflect transient cerebral functional abnormality accompanying fever or SIADH, whereas those in bacterial meningitis may result from neural tissue damage due to encephalopathy or angitis. In aseptic and bacterial meningitis, the presence of seizures in the acute phase was not correlated with the neurological outcome.     

Results of a regional study of modes of death associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group

BACKGROUND: It is well known that surgeon-specific in-hospital mortality rates for coronary artery bypass grafting vary, but this aggregate measure does not suggest specific opportunities for improvement. METHODS: We performed a regional prospective study of 8,641 consecutive patients undergoing isolated coronary artery bypass grafting by all of the 23 cardiothoracic surgeons practicing in northern New England during the study period. Mode of death was assigned by an end points committee using predetermined definitions. Surgeons were ranked according to risk-adjusted mortality rates and grouped in terciles, and cause-specific mortality rates were determined. RESULTS: The mortality rate was 3.3% in the lowest surgeon mortality tercile and 5.8% in the highest tercile. Fatal heart failure accounted for 80.0% of the difference in aggregate mortality rates, ranging from 1.9% in lowest surgeon mortality tercile to 4.0% in the highest tercile (p < 0.001). Rates of other causes did not differ significantly across surgeon mortality terciles. Differences in rates of fatal heart failure could not be explained by differences in preoperative left ventricular dysfunction or other patient characteristics. CONCLUSIONS: Most of the difference in observed mortality rates across surgeons is attributable to differences in rates of heart failure.     

Results of directional coronary atherectomy in Northern New England. Northern New England Cardiovascular Disease Study Group

The role of directional coronary atherectomy (DCA) in interventional cardiology remains uncertain. We report the Northern New England regional experience with DCA from 1991 to 1994. Data were collected on 11,178 patients having had an intervention on a single lesion in a single vessel (798 DCAs; 10,380 percutaneous transluminal angioplasties [PTCA]). The use of DCA increased from 1.8% of interventions in 1991 to 10% in 1994. Compared with PTCA, DCA patients were younger, more often men, had more 1-vessel disease and more coronary artery bypass surgery (CABG). DCA was more often used in the left anterior descending artery, in vein grafts, for restenoses, for subtotal occlusions, and with type A lesions. Angiographic success (96.7%) and clinical success (93%) were good. Adverse events were rare: mortality 0.9%, emergent CABG 2.2%, nonfatal myocardial infarction 2.8%. After adjusting for case-mix, there was no difference between DCA and PTCA for in-hospital mortality (odds ratio [OR] = 1.03, 95% confidence interval [CI] 0.44 to 2.43, p = 0.95) or need for emergent CABG (OR = 1.27, 95% CI 0.77 to 2.10, p = 0.34). Atherectomy patients were more likely to have a nonfatal myocardial infarction (OR = 2.0, 95% CI 1.26 to 3.20, p <0.01), to sustain an injury to the femoral or brachial artery (OR = 2.89, 95% CI 1.52 to 5.51, p <0.01), and to have a clinically successful procedure (OR = 1.37, 95% CI 1.01 to 1.88, p = 0.05). Our results support the relative safety and effectiveness of DCA as its use disseminated into the region.     

Prognostic value of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction. Investigators of this Multicenter Study

Reproductive aging in women is closely tied to the loss of ovarian follicles through atresia. The sentinel endocrinologic finding is the monotropic FSH rise, associated with a decline in ovarian inhibin B secretion. Fertility becomes significantly compromised long before overt clinical signs occur, such as cycle irregularity. Compromised fertility is primarily related to oocyte dysfunction. As women with regular cycles near the end of the reproductive years, the following changes are usually manifested: 1) the selection and development of a dominant follicle occurs earlier; 2) there is earlier ovulation; 3) there is a short follicular phase and total cycle length; and 4) ovarian steroid secretion is normal. The relationships, if any, between the monotropic FSH rise, accelerated follicular atresia, shortened follicular phase, and oocyte quality remain to be determined. The next phase of reproductive aging is the perimenopause. Lack of predictability is the rule with regard to the nature and duration of the perimenopause. Long cycles are interspersed with short ones, and intermittent ovulatory cycles are intermingled with periods that are hormonally indistinct from the postmenopausal state. Even after the last menstrual period, evidence of intermittent ovarian estradiol production may still be detected. Although fertility is severely compromised during the perimenopause, ovulation may occur without warning and contraception must be practiced if pregnancy is not desired. Further studies are needed to elucidate the factors contributing to oocyte abnormalities in women of advanced reproductive age, as well as the factors that determine the rate of follicle atresia and the length of the reproductive life span.     

The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group

BACKGROUND: Restricting protein intake and controlling hypertension delay the progression of renal disease in animals. We tested these interventions in 840 patients with various chronic renal diseases. METHODS: In study 1, 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were randomly assigned to a usual-protein diet or a low-protein diet (1.3 or 0.58 g of protein per kilogram of body weight per day) and to a usual- or a low-blood-pressure group (mean arterial pressure, 107 or 92 mm Hg). In study 2, 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were randomly assigned to the low-protein diet (0.58 g per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement, and a usual- or a low-blood-pressure group (same values as those in study 1). An 18-to-45-month follow-up was planned, with monthly evaluations of the patients. RESULTS: The mean follow-up was 2.2 years. In study 1, the projected mean decline in the glomerular filtration rate at three years did not differ significantly between the diet groups or between the blood-pressure groups. As compared with the usual-protein group and the usual-blood-pressure group, the low-protein group and the low-blood-pressure group had a more rapid decline in the glomerular filtration rate during the first four months after randomization and a slower decline thereafter. In study 2, the very-low-protein group had a marginally slower decline in the glomerular filtration rate than did the low-protein group (P = 0.07). There was no delay in the time to the occurrence of end-stage renal disease or death. In both studies, patients in the low-blood-pressure group who had more pronounced proteinuria at base line had a significantly slower rate of decline in the glomerular filtration rate. CONCLUSIONS: Among patients with moderate renal insufficiency, the slower decline in renal function that started four months after the introduction of a low-protein diet suggests a small benefit of this dietary intervention. Among patients with more severe renal insufficiency, a very-low-protein diet, as compared with a low-protein diet, did not significantly slow the progression of renal disease.     

Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Hokuriku-FH-LDL-Apheresis Study Group

BACKGROUND: Decreased muscle strength impedes elders' functional performance in daily activities such as gait. The mechanisms whereby increased strength improves gait are unknown. METHODS: A prospective, blinded, randomized trial of moderate intensity strength exercise was conducted and its impact was measured on functional mobility during gait in 132 functionally limited elders. Lower extremity strength was measured, including hip abductor, hip extensor, and knee extensor strength. Of the 132 subjects, 120 subjects (mean age, 75.1 yrs) completed 6 months of elastic band resistance training at least 3 times a week or served as no-exercise controls. RESULTS: Subjects increased their lower extremity strength in the exercise and control groups, by 17.6% and 7.3% (p < .01), respectively. Gait stability improved significantly more in the exercise group than in the control group (p < .05). Increases in forward gait velocity were not significantly different between groups. Peak mediolateral velocity and base of support improved in the exercise group, but not in the control group. Change in lower extremity strength correlated significantly but weakly with many of the gait variables. CONCLUSIONS: Gait stability, especially mediolateral steadiness, improved in the exercise group but not in the control group. These results show that even moderate strength gains benefit gait performance in elders and thus provide a sound basis for encouraging low-intensity strength training for elders with functional limitations.     

Modulation of lipoprotein(a) atherogenicity by high density lipoprotein cholesterol levels in middle-aged men with symptomatic coronary artery disease and normal to moderately elevated serum cholesterol. Regression Growth Evaluation Statin Study (REGRESS) Study Group

OBJECTIVES: This study sought to examine whether lipoprotein(a) levels predict coronary artery lumen changes in patients with symptomatic coronary artery disease (CAD) and normal to moderate hypercholesterolemia. BACKGROUND: Recent conflicting reports have confirmed or refuted the association of lipoprotein(a) with clinical events or angiographically verified disease progression. METHODS: The association between serum lipoprotein(a) and changes in coronary artery lumen was studied in 704 men entered into the Regression Growth Evaluation Statin Study (REGRESS), a double-blind, placebo-controlled, quantitative angiographic study that assessed the effect of 2 years of pravastatin treatment. The primary end points were changes in average mean segment diameter (MSD) and average minimal obstruction diameter (MOD). Pravastatin- and placebo-treated patients were classified as having progressing, regressing or stable CAD, and median lipoprotein(a) concentrations were compared. Bivariate and multivariate regression analyses were performed in the overall patient group and in high risk subgroups. RESULTS: Pravastatin treatment did not affect serum apolipoprotein(a) levels. Median in-trial (sampled at 24 months) apolipoprotein(a) levels for regressing, stable and progressing CAD were, respectively, 130, 162 and 251 U/liter in placebo-treated patients and 143, 224 and 306 U/liter in pravastatin-treated patients. Predictors of MSD and MOD changes were baseline MSD and MOD, in-trial apolipoprotein(a), in-trial high density lipoprotein (HDL) cholesterol and baseline use of long-acting nitrates. The multivariate models predicted 14% of MSD changes and 12% of MOD changes; apolipoprotein(a) predicted only 2.6% and 4.8%, respectively. However, in patients with in-trial HDL cholesterol levels <0.7 mmol/liter, apolipoprotein(a) predicted up to 37% of the arteriographic changes. CONCLUSIONS: Serum lipoprotein(a) levels predict coronary artery lumen changes in normal to moderately hypercholesterolemic white men with CAD; its atherogenicity is marked in the presence of concomitant hypoalphalipoproteinemia.     

Prognostic significance of systolic blood pressure changes during dobutamine-atropine stress technetium-99m sestamibi perfusion scintigraphy in patients with chest pain and known or suspected coronary artery disease

To investigate the prognostic value of dobutamine stress-induced changes in systolic blood pressure (BP) 418 patients (mean age 60 years, 238 men) with chest pain and known or suspected coronary artery disease, who underwent a dobutamine-atropine stress technetium-99m sestamibi myocardial perfusion scintigraphic study, were followed up for 25 +/- 15 months. Blood pressure was measured by automatic sphygmomanometry every 3 minutes. A marked decrease and increase in systolic BP from rest to peak were defined as changes of > or = 20 mm Hg, and > or = 30 mm Hg, respectively. Worst outcome events were cardiac death (n = 30), nonfatal myocardial infarction (n = 17), and hospitalization for congestive heart failure (n = 8). A decrease in systolic BP (prevalence 16%) was associated with older age and higher baseline systolic BP. Fixed and reversible sestamibi perfusion defects and follow-up results were similar to patients without a systolic BP decrease. In contrast, an increase in systolic BP (prevalence 24%) was associated with younger age, lower baseline systolic BP, and with absence of a history of prior congestive heart failure or treatment with angiotensin-converting enzyme inhibitors. Furthermore, these patients had fewer fixed perfusion defects and tended to have fewer annual event rates (3.5% vs 7.5%, p < 0.10). In a multivariate model, an increase in systolic BP was not an independent predictor for subsequent events. In conclusion, a dobutamine-induced decrease in systolic BP is not associated with fixed or reversible sestamibi defects or adverse prognosis. An increase in systolic BP, however, is associated with less fixed sestamibi defects and a tendency toward less annual event rates.