John Vessey

The Prevalence of Cardiac Valvular Insufficiency Assessed by Transthoracic Echocardiography in Obese Patients Treated with Appetite-Suppressant Drugs

BACKGROUND After case reports of cardiac-valve abnormalities related to the use of appetite suppressants were published, we undertook a study to determine the prevalence of the problem using transthoracic echocardiography. METHODS We examined patients who had taken dexfenfluramine alone, dexfenfluramine and phentermine, or fenfluramine and phentermine for various periods. We enrolled obese patients who had taken or were taking these agents during open-label trials from January 1994 through August 1997. We also recruited subjects who had not taken appetite suppressants and who were matched to the patients for sex, height, and pretreatment age and body-mass index. The presence of cardiac-valve abnormalities, defined by the Food and Drug Administration and Centers for Disease Control and Prevention as at least mild aortic-valve or moderate mitral-valve insufficiency, was determined independently by at least two cardiologists. Multivariate logistic-regression analysis was used to identify factors associated with cardiac-valve abnormalities. RESULTS Echocardiograms were available for 257 patients and 239 control subjects. The association between the use of any appetite suppressant and cardiac-valve abnormalities was analyzed in a final matched group of 233 pairs of patients and controls. A total of 1.3 percent of the controls (3 of 233) and 22.7 percent of the patients (53 of 233) met the case definition for cardiac-valve abnormalities (odds ratio, 22.6; 95 percent confidence interval, 7.1 to 114.2; P<0.001). The odds ratio for such cardiac-valve abnormalities was 12.7 (95 percent confidence interval, 2.9 to 56.4) with the use of dexfenfluramine alone, 24.5 (5.9 to 102.2) with the use of dexfenfluramine and phentermine, and 26.3 (7.9 to 87.1) with the use of fenfluramine and phentermine. CONCLUSIONS Obese patients who took fenfluramine and phentermine, dexfenfluramine alone, or dexfenfluramine and phentermine had a significantly higher prevalence of cardiac valvular insufficiency than a matched group of control subjects.

Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases

Elevated plasma homocysteine is increasingly being recognized as a risk factor for coronary artery disease (CAD). Although there is general agreement on the importance of micronutrients and genetic predisposition to elevated plasma homocysteine, the exact influence of the known prevalent mutations in genes which regulate homocysteine metabolism is not clear. We studied 376 cases of individuals with premature CAD with respect to their fasting and post-methionine load (PML) total homocysteine (tHcy) concentrations. We also determined the presence or absence of the T833C and G919A mutations of the cystathionine-beta-synthase (CBS) gene, the C677T mutation of the methylene tetrahydrofolate reductase (MTHFR) gene, and the A2756G transition of the B12 dependent methionine synthase (MS) gene. Our objectives were therefore both to confirm the relationship of plasma homocysteine with premature CAD and to examine the importance of genetic influence on both fasting and PML homocysteine. Approximately 32% of the CAD patients had fasting hyperhomocysteinemia and 16% had PML hyperhomocysteinemia. Of these, 8.5% had both forms of hyperhomocysteinemia (combined hyperhomocysteinemia). The T133C mutation in the CBS gene and the thermolabile C677T mutation in the MTHFR gene seem to play an important role in the subset of individuals with combined hyperhomocysteinemia. The A2756G transition in the MS gene is not associated with elevated plasma tHcy. Many cases (47%) of hyperhomocysteinemia are not associated with micronutrient deficiencies, impaired renal function, and/or currently known genetic mutations. Further work is needed to study whether unknown mutations, particularly those residing in the intronic sequences of the genes involved in homocysteine metabolism, other environmental factors, or interaction of gene, nutrient, and environmental factors may be the cause of currently unexplained cases of mild hyperhomocysteinemia.

The SUCCESS Project: The Effect of Program Format and Incentives on Participation and Cessation in Worksite Smoking Cessation Programs

OBJECTIVES This study examined the effect of program format and incentives on participation and cessation in worksite smoking cessation programs. METHODS Twenty-four worksites were randomized to 6 conditions that differed in cessation program format and the use of incentives. Programs were offered for 18 months in each worksite. A total of 2402 cigarette smokers identified at baseline were surveyed 12 and 24 months later to assess participation in programs and cessation. RESULTS A total of 407 (16.9%) of the smoker cohort registered for programs; on the 12- and 24-month surveys, 15.4% and 19.4% of the cohort, respectively, reported that they had not smoked in the previous 7 days. Registration for programs in incentive sites was almost double that of no-incentive sites (22.4% vs 11.9%), but increased registration did not translate into significantly greater cessation rates. Program type did not affect registration or cessation rates. CONCLUSIONS Although incentives increase rates of registration in worksite smoking cessation programs, they do not appear to increase cessation rates. Phone counseling seems to be at least as effective as group programs for promoting smoking cessation in worksites.

Predictors of quitting in hospitalized smokers

Hospitalization represents a teachable moment for quitting. The current study examined predictors of quitting among hospitalized smokers. Patients reported smoking history and demographic characteristics during in-hospital baseline interviews. Discharge diagnosis also was collected. Smoking status was ascertained in interviews at 7 days and at 12 months after discharge. A total of 2,350 patients in four Minneapolis and St. Paul (Twin Cities), Minnesota, area hospitals participated in the study; 1,477 patients who provided data at both follow-ups and whose 12-month self-report of quitting was corroborated by cotinine analysis of saliva samples were included in the current analyses. Predictors of both short- and long-term abstinence in the multivariate analysis included smoking-related illness, age (those who were older were more likely to be abstinent), stage of change (precontemplators were least likely to quit, and those initially in action were most likely to quit), and time to first cigarette (those who reported smoking within 5 min of awakening were least likely to quit). The predictors presented few surprises; the most important finding may have been that the experience of hospitalization itself led to substantial long-term quitting for virtually all categories of hospitalized smokers.

Factors Associated with the Risk of Liver Enzyme Elevation in Patients with Type 2 Diabetes Treated with a Thiazolidinedione

Study Objective. To characterize frequency of liver enzyme elevation in patients with type 2 diabetes mellitus receiving troglitazone.