Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia.

BACKGROUND: Improving lipids beyond low-density lipoprotein cholesterol (LDL-C) lowering with statin monotherapy may further reduce cardiovascular risk. Niacin has complementary lipid-modifying efficacy to statins and cardiovascular benefit, but is underutilised because of flushing, mediated primarily by prostaglandin D(2) (PGD(2)). Laropiprant (LRPT), a PGD(2) receptor (DP1) antagonist that reduces niacin-induced flushing has been combined with extended-release niacin (ERN) into a fixed-dose tablet. METHODS AND RESULTS: Dyslipidaemic patients were randomised to ERN/LRPT 1 g (n = 800), ERN 1 g (n = 543) or placebo (n = 270) for 4 weeks. Doses were doubled (2 tablets/day; i.e. 2 g for active treatments) for 20 weeks. ERN/LRPT 2 g produced significant changes vs. placebo in LDL-C (-18.4%), high-density lipoprotein cholesterol (HDL-C; 20.0%), LDL-C:HDL-C (-31.2%), non-HDL-C (-19.8%), triglycerides (TG; -25.8%), apolipoprotein (Apo) B (-18.8%), Apo A-I (6.9%), total cholesterol (TC; -8.5%), TC:HDL-C (-23.1%) and lipoprotein(a) (-20.8%) across weeks 12-24. ERN/LRPT produced significantly less flushing than ERN during initiation (week 1) and maintenance (weeks 2-24) for all prespecified flushing end-points (incidence, intensity and discontinuation because of flushing). Except for flushing, ERN/LRPT had a safety/tolerability profile comparable with ERN. CONCLUSION: Extended-release niacin/LRPT 2 g produced significant, durable improvements in multiple lipid/lipoprotein parameters. The improved tolerability of ERN/LRPT supports a simplified 1 g-->2 g dosing regimen of niacin, a therapy proven to reduce cardiovascular risk.

Variations in cholesterol management practices of U.S. physicians.

OBJECTIVES: This study sought to evaluate national cholesterol management practices of U.S. physicians. BACKGROUND: Past studies show that nonclinical factors affect physician practices. We tested the hypothesis that physician and patient characteristics influence cholesterol management. METHODS: We used a stratified, random sample of 2,332 office-based physicians providing 56,215 visits to adults in the 1991-1992 National Ambulatory Medical Care Surveys. We investigated physicians' reporting of cholesterol-related screening, counseling or medications during office visits and used multiple logistic regression to assess independent predictors. RESULTS: An estimated 1.12 billion adult office visits occurred in 1991 and 1992 (95% confidence interval 1.06 to 1.18 billion). For the 1.03 billion visits by patients without reported hyperlipidemia, cholesterol screening (2.8% of visits) and counseling (1.2%) were not frequent. The likelihood of screening increased with older age, cardiovascular disease risk factors, white race and private insurance. We estimate that only 1 in 12 adults received cholesterol screening annually. In the 85 million visits by patients with hyperlipidemia, cholesterol testing was reported in 22.9%, cholesterol counseling in 34.4% and lipid-lowering medications in 23.1%. Testing was more likely in diabetic and nonobese patients. Counseling was more likely with younger age, cardiovascular disease and private insurance. Medications use was associated with cardiovascular disease, Northeast region of the United States, nonobese patients and visits to internists. Physician practices did not differ by patient gender. CONCLUSIONS: Although clinical conditions strongly influence cholesterol management, the appropriateness of variations noted by payment source, geographic region and physician specialty deserve further evaluation. These variations and the low estimated volume of services suggest that physicians have not fully adopted recommended cholesterol management practices.

Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group.

OBJECTIVES: This randomized clinical trial tested whether fish oil supplements can improve human coronary atherosclerosis. BACKGROUND: Epidemiologic studies of populations whose intake of oily fish is high, as well as laboratory studies of the effects of the polyunsaturated fatty acids in fish oil, support the hypothesis that fish oil is antiatherogenic. METHODS: Patients with angiographically documented coronary heart disease and normal plasma lipid levels were randomized to receive either fish oil capsules (n = 31), containing 6 g of n-3 fatty acids, or olive oil capsules (n = 28) for an average duration of 28 months. Coronary atherosclerosis on angiography was quantified by computer-assisted image analysis. RESULTS: Mean (+/- SD) baseline characteristics were age 62 +/- 7 years, plasma total cholesterol concentration 187 +/- 31 mg/dl (4.83 +/- 0.80 mmol/liter) and triglyceride levels 132 +/- 70 mg/dl (1.51 +/- 0.80 mmol/liter). Fish oil lowered triglyceride levels by 30% (p = 0.007) but had no significant effects on other plasma lipoprotein levels. At the end of the trial, eicosapentaenoic acid in adipose tissue samples was 0.91% in the fish oil group compared with 0.20% in the control group (p < 0.0001). At baseline, the minimal lumen diameter of coronary artery lesions (n = 305) was 1.64 +/- 0.76 mm, and percent narrowing was 48 +/- 14%. Mean minimal diameter of atherosclerotic coronary arteries decreased by 0.104 and 0.138 mm in the fish oil and control groups, respectively (p = 0.6 between groups), and percent stenosis increased by 2.4% and 2.6%, respectively (p = 0.8). Confidence intervals exclude improvement by fish oil treatment of > 0.17 mm, or > 2.6%. CONCLUSIONS: Fish oil treatment for 2 years does not promote major favorable changes in the diameter of atherosclerotic coronary arteries.

Cost-effectiveness of a smoking cessation program after myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the cost-effectiveness of a smoking cessation program initiated after acute myocardial infarction. BACKGROUND: The value of allocating health care resources to smoking cessation programs after myocardial infarction has not been compared with the value of other currently accepted interventions. METHODS: A model was developed to examine the cost-effectiveness of a recently reported smoking cessation program after an acute myocardial infarction. The cost was estimated by considering the resources necessary to implement the program, and the effectiveness was expressed as discounted years of life saved. Years of life saved were estimated by modeling life expectancy using a single declining exponential approximation of life expectancy based on data from published reports. RESULTS: The cost-effectiveness of the nurse-managed smoking cessation program was estimated to be $220/year of life saved. In a one-way sensitivity analysis, the cost-effectiveness of the program remained < $20,000/year of life saved if the program decreased the smoking rate by only 3/1,000 smokers (baseline assumption 26/100 smokers), or if the program cost as much as $8,840/smoker (baseline assumption $100). In a two-way sensitivity analysis, even if the cost of the program were as high as $2,000/participant, the cost-effectiveness of the program would be < $10,000/year of life saved so long as the program helped an additional 12 smokers quit for every 100 enrolled. CONCLUSIONS: Over a wide range of estimates of costs and effectiveness, a nurse-managed smoking cessation program after acute myocardial infarction is an extremely cost-effective intervention. This program is more cost-effective than beta-adrenergic antagonist therapy after myocardial infarction.

Incidence and management of limb ischemia with percutaneous wire-guided intraaortic balloon catheters.

In 103 patients who underwent placement of 106 percutaneous wire-guided intraaortic balloon catheters between August 1983 and January 1986, all placements were successful and the average duration of counterpulsation was 3.4 +/- 1.6 days. During counterpulsation, 45 patients developed limb ischemia that required premature balloon removal in 29 patients. The development of limb ischemia was significantly related to the presence of diabetes (risk ratio 2.0), peripheral vascular disease (risk ratio 1.9), female gender (risk ratio 1.8) and the presence of a postinsertion ankle-brachial pressure index less than 0.8 (risk ratio 7.9). There was no association between the development of limb ischemia and age, body surface area, balloon size (10.5F/12F) or adequacy of anticoagulation. Fifteen patients underwent vascular surgery for treatment of balloon-related limb ischemia, which was associated with one operative death. Nine patients had persistent limb ischemia (seven asymptomatic, two symptomatic) at the time of hospital discharge. Improvements in wire-guided balloon technology have increased the probability of successful balloon placement over that of surgical placement and have reduced the incidence of major aortic injury, but there is no evidence that these improvements have reduced the incidence of limb ischemia or its sequelae. This should be borne in mind before proceeding with balloon insertion in patients with one or more risk factors for developing limb ischemia.

Assessment of left ventricular end-systolic pressure-volume relations with an impedance catheter and transient inferior vena cava occlusion: use of this system in the evaluation of the cardiotonic effects of dobutamine, milrinone, Posicor and epinephrine.

The end-systolic pressure-volume relation has been postulated as a load-independent measure of cardiac contractility, but has been difficult to measure because of technical problems associated with the serial measurement of intracardiac volume over a physiologic range of ventricular loading conditions. Utilizing a multielectrode impedance catheter to assess continuous, on-line left ventricular relative volume during transient inferior vena cava occlusion, a method is described for determining the end-systolic pressure-volume relation and for assessing changes in this relation secondary to inotropic modulation. In particular, using this method, the relative inotropic properties were determined of four drugs: dobutamine, milrinone, epinephrine and an experimental cardiotonic agent (Ro 13-6438, Posicor). Left ventricular micromanometer pressure and impedance catheter volume were measured continuously in 10 open chest, anesthetized dogs and 14 pigs. Arterial pressure was altered over a range of 20 to 60 mm Hg by brief inferior vena cava constriction. A linear end-systolic pressure-volume relation was observed in pressure-volume diagrams constructed from on-line pressure and impedance catheter recordings. Administration of dobutamine, milrinone and epinephrine resulted in a leftward shift and an increase in the slope of the end-systolic pressure-volume relation as compared with baseline; Posicor did not alter the slope over a range of doses, despite an increase in the cardiac output secondary to arterial vasodilation. Volume changes as measured by the impedance method closely paralleled simultaneous changes in the ultrasonic crystal-determined segment length, and the impedance end-systolic pressure-volume relation slope was reproducible with repeated load-altering maneuvers.(ABSTRACT TRUNCATED AT 250 WORDS)

Duration of neuroleptic treatment and prevalence of tardive dyskinesia in late life.

BACKGROUND: Although increasing age is the most consistently cited risk factor for the development of tardive dyskinesia for patients in the second to sixth decades of life, this relationship may not hold within geriatric populations. METHODS: Consecutively admitted geropsychiatric inpatients were examined with the Abnormal Involuntary Movement Scale within 72 hours of admission; comprehensive demographic, diagnostic, and psychometric data were also obtained. RESULTS: Seventy-four (19.2%) of 386 patients received diagnoses of dyskinesia. Lifetime duration of neuroleptic use was strongly correlated with dyskinesia rates. After accounting for the effect of lifetime duration of neuroleptic use in a stepwise logistic regression, only associations with Global Assessment Scale score and presence of dental problems remained statistically significant. In comparison with the duration of neuroleptic use, however, the contribution of these factors was minor. Sixteen percent of patients with less than 3 months of neuroleptic use, 29% with 3 to 12 months of neuroleptic use, 30% with 1 to 10 years of neuroleptic use, and 41% with more than 10 years of neuroleptic use had dyskinesia. Compared with patients with no history of neuroleptic treatment, the relative risks for these durations of neuroleptic use were 1.62 (95% confidence limits [CL], 0.81, 3.24), 2.89 (95% CL, 1.50, 5.55), 3.08 (95% CL, 1.66, 5.70), and 4.11 (95% CL, 2.12, 7.96), respectively. CONCLUSIONS: Within elderly populations, duration of exposure to neuroleptics is the strongest predictor of risk for tardive dyskinesia, and this risk increases rapidly within the first year of total lifetime neuroleptic use.

Efficacy of a smoking cessation program for hospital patients.

BACKGROUND: Hospitalization may be an opportune time to change smoking behavior because it requires smokers to abstain from tobacco at the same time that illness can motivate them to quit. A hospital-based intervention may promote smoking cessation after discharge. METHODS: We tested the efficacy of a brief bedside smoking counseling program in a randomized controlled trial at Massachusetts General Hospital, Boston. The 650 adult smokers admitted to the medical and surgical services were randomly assigned to receive usual care or a hospital-based smoking intervention consisting of (1) a 15-minute bedside counseling session, (2) written self-help material, (3) a chart prompt reminding physicians to advise smoking cessation, and (4) up to 3 weekly counseling telephone calls after discharge. Smoking status was assessed 1 and 6 months after hospital discharge by self-report and validated at 6 months by measurement of saliva cotinine levels. RESULTS: One month after discharge, more intervention than control patients were not smoking (28.9% vs 18.9%; P=.003). The effect persisted after multiple logistic regression analyses adjusted for baseline group differences, length of stay, postdischarge smoking treatment, and hospital readmission (adjusted odds ratio, 2.19; 95% confidence interval, 1.34-3.57). At 6 months, the intervention and control groups did not differ in smoking cessation rate by self-report (17.3% vs 14.0%; P=.26) or biochemical validation (8.1% vs 8.7%; P=.72), although the program appeared to be effective among the 167 patients who had not previously tried to quit smoking (15.3% vs 3.7%; P=.01). CONCLUSIONS: A low-intensity, hospital-based smoking cessation program increased smoking cessation rates for 1 month after discharge but did not lead to long-term tobacco abstinence. A longer period of telephone contact after discharge might build on this initial success to produce permanent smoking cessation among hospitalized smokers.

In vivo regulation of hemopoiesis by transforming growth factor beta 1: stimulation of GM-CSF- and M-CSF-dependent murine bone marrow precursors.

Injection of mice with either natural bovine bone-derived or human recombinant transforming growth factor beta 1 (TGF-beta 1) resulted in a significant increase of the macrophage and macrophage-granulocyte-forming capacity of their macrophage colony-stimulating factor (M-CSF)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent bone marrow precursor cells. The increased potential for generating granulocytes and/or macrophages from bone marrow cells of mice injected with TGF-beta 1 was associated with an increase of the number of M-CSF- and GM-CSF-dependent bone marrow colony-forming units (CFU). The effect was selective, in that in vivo applied TGF-beta 1 did not affect interleukin 3 (IL-3)-dependent CFU. The data suggest that TGF-beta may be useful in recovery of bone marrow granulocyte- and macrophage-forming potentials following depletion caused by chemo- or radiotherapy.

Medical comorbidity in elderly psychiatric inpatients.

A multidisciplinary diagnostic evaluation was performed for 868 older psychiatric inpatients during a 46-month interval. A total of 402 (46%) met DSM-III-R criteria for organic mental disorders, 329 (38%) had mood disorders, 90 (10%) had psychotic disorders, and 47 (5%) had other mental disorders or conditions. Concurrent medical problems were systematically assessed and classified according to ICD-9-CM criteria. The patients suffered from a mean of 5.6 +/- 3.1 (SD) active medical problems (range 0-18). This level of medical comorbidity was significantly greater than that of older psychiatric outpatients and comparable to that of elderly inpatients in general medical hospitals. When the effects of age and education were controlled for, there were no significant differences in mean numbers of medical problems among the four groups of psychiatric inpatients. An association of major depression with diseases of the digestive system was observed and may be related to peripheral autonomic dysregulation.

Sleep after spousal bereavement: a study of recovery from stress.

AIM: In this study, we compared repeated measures of electroencephalographic (EEG) sleep and subjective sleep quality in nondepressed, spousally bereaved elders and a healthy control group, in order to search for possible psychobiological correlates of bereavement not confounded by concurrent major depression. METHOD: Laboratory-based EEG sleep studies and measures of subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were repeated at 3, 6, 11, 18, and 23 months after spousal bereavement in a study group of 27 elderly volunteers. Data were compared with similar measures from a control group of 27 nonbereaved subjects recorded on three occasions 1 year apart. Repeated-measures analysis of variance (ANOVA), using age as a covariate, examined effects due to time on selected variables in the bereaved group, as well as effects due to group, time, and group-by-time interactions in the experimental and control subjects. RESULTS: Bereaved and control groups showed consistent differences over time in the phasic measures of rapid eye movement (REM) sleep (higher in bereaved subjects during the first and third REM sleep periods), but were similar on all other EEG sleep measures over the 2 years of observation. The bereaved showed a small decline in the percentage of slow-wave sleep over 2 years, but measures of sleep efficiency, REM latency, and delta sleep ratio were stable and did not differ from values seen in control subjects. Bereaved and control subjects were also similar on subjective sleep quality. CONCLUSION: During successful adaptation to the loss of a spouse, and in the absence of major depression, spousal bereavement is associated with elevation in the phasic measures of REM sleep but does not appear to be associated with other physiologic sleep changes typical of major depression when studied at 3 to 23 months after the event. Although this observation does not preclude the possibility of significant sleep disturbance nearer the time of the event, it suggests that preservation of normal sleep following a major negative life event may be an important correlate of the resilience seen in successful aging. The elevation in REM density may provide a psychobiological correlate of bereavement not confounded by concurrent major depression.

Mortality of elderly patients with psychiatric disorders.

OBJECTIVE: The goal of this study was to evaluate the impact of common late-life mental disorders on the life expectancy and causes of death of older psychiatric patients. METHOD: The study population consisted of 809 older psychiatric patients who met DSM-III-R criteria for organic mental disorders, mood disorders, or psychotic disorders and who were discharged after a comprehensive multidisciplinary evaluation and acute inpatient treatment for their behavioral disorders. Dates and causes of death during a 5.75-year follow-up period were provided by the Pennsylvania Department of Health. Univariate and multivariate survival procedures were used to compare the survival rates of the three groups to each other and to a reference population of Pennsylvania residents. Causes of death were also tabulated according to ICD-9-CM and compared across the groups. RESULTS: Age, gender, race, and medical comorbidity made significant independent contributions to survival. When these variables were controlled, the survival of patients with organic mental disorders was less than half of that for patients with mood or psychotic disorders. However, all three groups experienced higher rates of mortality than the reference population, with standardized mortality ratios of 1.5 to 2.5. Deaths occurred from the usual spectrum of natural causes, with the exception that patients with mood disorders were more likely to have died from disorders of the digestive system and suicide. CONCLUSIONS: The mental disorders of late life have a significant negative impact on the survival of older psychiatric patients.

Diagnostic rate of comorbid personality disorder in elderly psychiatric inpatients.

Among 547 elderly inpatients grouped by DSM-III-R axis I diagnoses, the diagnostic rate of comorbid personality disorder varied four-fold, from 6% in patients with an organic mental disorder to 24% in those with major depression. The previously reported low prevalence of comorbid personality disorder in geriatric patients may be due to its lower rate of diagnosis among patients with organic mental disorders.

Impact of acute psychiatric inpatient treatment on major depression in late life and prediction of response.

OBJECTIVE: The authors conducted a prospective study to examine the sociodemographic and clinical characteristics of elderly inpatients with major depression and their response to acute psychiatric hospitalization. The relation between the descriptive variables and clinical response was also investigated. METHOD: The subjects were 205 consecutively admitted inpatients, whose mean age was 71 years, who met the DSM-III-R criteria for major depression. Each subject received detailed physical, psychiatric, and mental status examinations, along with quantitative assessments of psychiatric symptoms and cognitive performance at admission and at discharge. Management of physical problems was optimized, and patients were treated with a combination of somatic and psychotherapeutic interventions. The average duration of hospitalization was approximately 1 month. RESULTS: Despite considerable medical and psychiatric comorbidity, the patients responded well to treatment, as reflected by a 50% reduction in the average score on the Hamilton Depression Rating Scale. Nearly one-half of the patients had experienced the resolution of their depressive symptoms by the time of discharge. Race, cognitive performance at admission, number of medical problems, use of ECT, and length of hospitalization independently contributed to the prediction of clinical response. Response to treatment was not related to the other sociodemographic variables examined or to any of the indexes of severity of depressive episode. CONCLUSIONS: Short-term psychiatric hospitalization offers an effective and efficient vehicle for the treatment of severe or complicated cases of major depression in the elderly, even when considerable medical and psychiatric comorbidity is present.

Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy.

OBJECTIVE: The authors tested the hypothesis that nortriptyline and interpersonal psychotherapy, alone and in combination, are superior to placebo in achieving remission of bereavement-related major depressive episodes. METHOD: Eighty subjects, aged 50 years and older, with major depressive episodes that began within 6 months before or 12 months after the loss of a spouse or significant other were randomly assigned to a 16-week doubleblind trial of one of four treatment conditions: nortriptyline plus interpersonal psychotherapy (N = 16), nortriptyline alone in a medication clinic (N = 25), placebo plus interpersonal psychotherapy (N = 17), or placebo alone in a medication clinic (N = 22). The protocol required that the acute-phase double-blind treatment be ended after 8 weeks if Hamilton depression scale ratings had not improved by 50%. Remission was defined as a 17-item Hamilton scale score of 7 or lower for 3 consecutive weeks. RESULTS: The rate of remission for nortriptyline plus interpersonal psychotherapy was 69% (N = 11); for medication clinic, nortriptyline, 56% (N = 14); for placebo plus interpersonal psychotherapy, 29% (N = 5); and for medication clinic, placebo, 45% (N = 10). In a generalized logit model, there was a significant effect of nortriptyline over placebo but no interpersonal psychotherapy effect and no nortriptyline-by-interpersonal psychotherapy interaction. Rates of all-cause attrition were lowest in the nortriptyline plus interpersonal psychotherapy group. CONCLUSIONS: Nortriptyline was superior to placebo in achieving remission of bereavement-related major depressive episodes. The combination of medication and psychotherapy was associated with the highest rate of treatment completion. These results support the use of pharmacologic treatment of major depressive episodes in the wake of a serious life stressor such as bereavement.

Comparison of the absorption and effect on platelet function of a single dose of n-3 fatty acids given as fish or fish oil.

To compare their relative absorption and effect on platelet function, concentrated fish oil and tuna were given to 10 subjects in a randomized crossover study. Although plasma enrichment of eicosapentaenoic acid (EPA) from either preparation was similar, relative absorption of EPA from tuna was significantly greater than that from fish oil (46.6 +/- 3.0 mg.L-1.g EPA-1 from tuna compared with 16 +/- 1.0 mg.L-1.g EPA-1 from fish oil, P less than 0.001). Relative absorption of docosahexaenoic acid (DHA) was equivalent (54.0 +/- 9.0 mg.L-1.g DHA-1 from tuna, 56 +/- 9.0 mg.L-1.g DHA-1 from fish oil, NS). Platelet aggregation in response to the endoperoxide analog U46619 was significantly diminished after either preparation but aggregation in response to other agonists, bleeding time, and membrane n-3 (omega-3) fatty acid content were not changed. Thus, n-3 fatty acids are well absorbed after one dose of either tuna or fish oil but EPA absorption appears to be more efficient from tuna. Additionally, a single dose of n-3 fatty acids decreases platelet aggregation by a mechanism not requiring incorporation into platelet membranes.

Clinical angiographic regression of atherosclerosis after partial ileal bypass.

Clinical documentation of atherosclerotic plaque regression has been difficult to obtain. This is a report of a patient with severe and early atherosclerotic cardiovascular disease with regression of at least three major atherosclerotic lesions demonstrated by coronary arteriography 10 years after partial ileal bypass operation. The patient's total plasma cholesterol was reduced over these 10 years, ranging from 40% to 23%, from the preoperative level of 757 mg/dl. Sequential arteriograms were assessed independently by several arteriographers and blindly by the Arteriography Review Panel of the Program on Surgical Control of the Hyperlipidemias (POSCH). The readings were analyzed by 4 grading methods. Unanimously, marked regression was read in the proximal left circumflex artery (70% leads to 20%), middle segment of the right coronary artery (45% leads to 20%), and in the distal right coronary artery (80% leads to 50%). Thus, by any and all of the methods used, there was significant regression of arteriographically demonstrated atherosclerotic lesions.

Enhanced rate of progression of coronary artery disease following aortocoronary saphenous vein bypass surgery.

To evaluate the fate of the boronary arteries after aortocoronary bypass, 40 patients underwent serial selective coronary angiographic studies 1 year apart, and the frequency of progression of coronary artery disease was estimated. Thirty-two had saphenous vein bypass surgery after the first procedure, six had Vineberg operations, and two had no interim operation. In each patient, the right, left, anterior descending and circumflex coronary arteries (including their branches) were separately evaluated. Progressive narrowing was evident in 31 of 50 (62 per cent) bypassed vessels and in only 11 to 113 (9.7 per cent) nonbypassed arteries (p less than 0.001). Coronary arteries with moderate to severe obstruction initially (50 to 99 per cent occluded) manifested progressive diseasee more frequently (33 of 70 arteries) than did arteries that were normal or mildly narrowed initially (4 of 71) (p less than 0.001. Considering only those vessels with 50 to 99 per cent obstruction initially, 27 of 35 (77 per cent) of the bypassed arteries and only 6 of 35 (17 per cent) of the nonbypassed arteries showed progression (p less than 0.001). We conclude that moderately or severely narrowed coronary arteries are more likely to show progressive narrowing than normal or mildly obstructed ones and that progression of coronary disease is greater in bypassed vessels than in nonbypassed vessels. In view of potential graft closure, the implications of these findings must be considered in selecting patients for aortocoronary bypass.

High-density lipoprotein subfractions.

High-density lipoprotein (HDL) consists of a heterogeneous group of particles defined either by size or by apolipoprotein content. Subfractions of HDL appear to have distinct but interrelated metabolic functions, including facilitation of cholesteryl ester transfer to low- and very-low-density lipoproteins, modulation of triglyceride-rich particle catabolism, and, possibly, removal of cholesterol from peripheral tissues. Like HDL cholesterol, HDL subfractions are widely affected by a variety of factors. Subfractions also are markers for epidemiologic risk for coronary artery disease. Because they provide information about the physiologic processes of cholesterol metabolism, HDL subfractions are emerging as an increasingly important tool in the study of the relationship between lipids and cardiovascular disease.

Chest pain with angiographically insignificant coronary arterial obstruction. Clinical presentation and long-term follow-up.

Among 3,242 coronary angiograms performed from November 1972 through October 1975 at the Massachusetts General Hospital, 175 patients had normal coronary arteries or luminal narrowings of less than 30 per cent. All patients were studied for chest pain, and none had experienced prior myocardial infarction. Subsequent information was available in 159 patients over a mean follow-up period of 42.7 months. There were no deaths, and only one myocardial infarction occurred during this period. However, among the patients followed, continued chest pain with episodes occurring at least once monthly was present in 54 per cent. In addition, 17 per cent of all patients required subsequent hospitalization and 44 per cent continued to receive antianginal medication. Nearly half of the group (46 per cent) suffered some limitation of activity, and 22 per cent stated that they had either changed jobs or stopped work because of chest pain. Continuing chest pain was significantly more common in women and in patients who had experienced chest pain for more than one year before angiography. However, typicality of chest pain for angina or the occurrence of electrocardiographic changes of ischemia prior to angiography did not predict continued chest pain during the follow-up period. Thus, although mortality and morbidity are low in this group of patients, the syndrome of chest pain with angiographically insignificant coronary artery obstruction has an important impact on the lives of a majority of those affected.