Chirayath Suchindran

Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study.

A cohort of 2270 white women, aged 40-69 years at baseline, were followed for an average of 8.5 years in the Lipid Research Clinics Program Follow-up Study. There were 44 deaths due to cardiovascular disease among the 1677 nonusers of estrogens and six cardiovascular disease deaths among the 593 estrogen users. The age-adjusted relative risk (RR) of cardiovascular disease deaths in users compared with nonusers was 0.34 (95% confidence limits 0.12 to 0.81). After multivariable adjustment for potential confounding factors (age, blood pressure, and smoking), the estimated RR for estrogen use was 0.37 (95% confidence limits 0.16 to 0.88). Analyses were done to explore whether these results could be due to selection bias for estrogen use. However, the prevalence of cardiovascular disease at baseline was slightly higher in estrogen users (12%) than in nonusers (10%); furthermore, the exclusion of all women with prevalent cardiovascular disease at baseline did not alter the apparent protective effect of estrogen...

Plasma Triglyceride Level and Mortality from Coronary Heart Disease

BACKGROUND Whether the plasma triglyceride level is a risk factor for coronary heart disease has been controversial, and evaluation of the triglyceride level as a risk factor is fraught with methodologic difficulties. METHODS We studied the association between plasma triglyceride levels and the 12-year incidence of death from coronary heart disease in 10 North American populations participating in the Lipid Research Clinics Follow-up Study, while adjusting for the potential confounding effects of other risk factors for cardiovascular disease, including the level of high-density lipoprotein (HDL) cholesterol. All analyses were sex-specific, and separate analyses were performed in high and low strata of HDL cholesterol, low-density lipoprotein (LDL) cholesterol, fasting plasma glucose, and age. RESULTS The rates of coronary death in both men and women increased with the triglyceride level. In Cox proportional-hazards models adjusted for age, in which the natural log of the triglyceride levels was used to give a normal distribution, the relative risk per natural-log unit of triglyceride (e.g., a triglyceride level of 150 mg per deciliter vs. a level of 55 mg per deciliter) was 1.54 (95 percent confidence interval, 1.19 to 1.98; P < 0.001) in men and 1.88 (95 percent confidence interval, 1.19 to 2.98; P < 0.007) in women. After an adjustment for potential covariates, however, these relative risks were not statistically significant. Analyses based on lipoprotein cholesterol levels revealed a positive association between the triglyceride level and coronary mortality in the lower stratum of both HDL and LDL cholesterol, but not in the higher stratum. Conversely, the HDL cholesterol level was unrelated to coronary mortality in the lower stratum of LDL cholesterol, but was strongly inversely associated with coronary death in the higher stratum of LDL cholesterol. The relative risk of coronary death associated with triglyceride level was higher at younger ages. The associations between the triglyceride level and coronary mortality in the lower HDL cholesterol, LDL cholesterol, and age strata were small and were further reduced by an adjustment for the fasting plasma glucose level. CONCLUSIONS Overall, the plasma triglyceride level showed no independent association with coronary mortality. However, in subgroups of subjects with lower HDL and LDL cholesterol levels and in younger subjects, defined a priori, an association between the triglyceride level and coronary mortality was observed, although this association was small and was not statistically significant after an adjustment for the plasma glucose level.

Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: Evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis

Objective To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death. Design Evaluation of recovered data from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73; and an updated meta-analysis including these previously missing data. Setting Ambulatory, coronary care clinic in Sydney, Australia. Participants 458 men aged 30-59 years with a recent coronary event. Interventions Replacement of dietary saturated fats (from animal fats, common margarines, and shortenings) with omega 6 linoleic acid (from safflower oil and safflower oil polyunsaturated margarine). Controls received no specific dietary instruction or study foods. All non-dietary aspects were designed to be equivalent in both groups. Outcome measures All cause mortality (primary outcome), cardiovascular mortality, and mortality from coronary heart disease (secondary outcomes). We used an intention to treat, survival analysis approach to compare mortality outcomes by group. Results The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6% v 11.8%, hazard ratio 1.62 (95% confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04). Inclusion of these recovered data in an updated meta-analysis of linoleic acid intervention trials showed non-significant trends toward increased risks of death from coronary heart disease (hazard ratio 1.33 (0.99 to 1.79); P=0.06) and cardiovascular disease (1.27 (0.98 to 1.65); P=0.07). Conclusions Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats. Trial registration Clinical trials NCT01621087.

Assessing the Long-Term Effects of the Safe Dates Program and a Booster in Preventing and Reducing Adolescent Dating Violence Victimization and Perpetration

OBJECTIVES This study determined 4-year postintervention effects of Safe Dates on dating violence, booster effects, and moderators of the program effects. METHODS We gathered baseline data in 10 schools that were randomly allocated to a treatment condition. We collected follow-up data 1 month after the program and then yearly thereafter for 4 years. Between the 2- and 3-year follow-ups, a randomly selected half of treatment adolescents received a booster. RESULTS Compared with controls, adolescents receiving Safe Dates reported significantly less physical, serious physical, and sexual dating violence perpetration and victimization 4 years after the program. The booster did not improve the effectiveness of Safe Dates. CONCLUSIONS Safe Dates shows promise for preventing dating violence but the booster should not be used.

Epidermolysis bullosa and the risk of life-threatening cancers : The National EB Registry experience, 1986-2006

BACKGROUND Case series have demonstrated that potentially lethal cutaneous squamous cell carcinomas arise in patients with recessive dystrophic epidermolysis bullosa (RDEB), although the magnitude of this risk is undefined. METHODS Systematic case finding and data collection were performed throughout the continental United States (1986-2002) by the National EB Registry on 3280 EB patients to determine cumulative and conditional risks for squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM) within each major EB subtype, as well as the cumulative risk of death from each tumor. Study design was cross-sectional, with a nested randomly sampled longitudinal subcohort (N = 450). RESULTS SCCs arose primarily in RDEB, especially the Hallopeau-Siemens subtype (RDEB-HS), first beginning in adolescence. Less frequently, SCCs occurred in junctional EB (JEB). Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively. In Herlitz JEB, the risk was 18.2% by age 25. SCC deaths occurred only in RDEB, with cumulative risks in RDEB-HS of 38.7%, 70.0%, and 78.7% by ages 35, 45, and 55, respectively. MM arose in RDEB-HS, with a cumulative risk of 2.5% by age 12. BCCs arose almost exclusively in the most severe EB simplex subtype (Dowling-Meara) (cumulative risk = 43.6% by age 55). LIMITATIONS Mutational analyses were performed on only a minority of enrollees in the National EB Registry, preventing evaluation of the possible influence of specific genotypes on the risk of developing or dying from cutaneous SCCs. CONCLUSIONS SCC is the most serious complication of EB within adults, especially those with RDEB-HS. By mid-adulthood, nearly all will have had at least one SCC, and nearly 80% will have died of metastatic SCC despite aggressive surgical resection. When compared with SCCs arising within the normal population, the remarkably high risk of occurrence of and then death from SCCs among RDEB patients suggests likely differences in pathogenesis. Additional studies of EB-derived tumors and SCC cell lines may not only provide new insights into the mechanisms of carcinogenesis but also means whereby these particular tumors may be prevented or more effectively treated.

Smart Teens Don't Have Sex (or Kiss Much Either)

PURPOSE To examine the relationship between an intelligence measure and a wide spectrum of partnered sexual activity ranging from holding hands to sexual intercourse among adolescents. METHOD Analyses are based on two separate samples of adolescents. The core sample of the National Longitudinal Study of Adolescent Health (Add Health) includes approximately 12,000 adolescents enrolled in the 7th to 12th grades. The Biosocial Factors in Adolescent Development projects followed approximately 100 white males and 200 black and white females over 3- and 2-year periods, respectively. Both studies used the Peabody Picture Vocabulary Test (PPVT) as an intelligence measure, and confidential self-reports of sexual activity. Logistic regression models were used to examine the relationship between PPVT scores and coital status in Add Health data; proportional hazard models were used to examine the timing of initiation of noncoital and coital activities as a function of PPVT scores in the Biosocial Factors sample. RESULTS Controlling for age, physical maturity, and mothers education, a significant curvilinear relationship between intelligence and coital status was demonstrated; adolescents at the upper and lower ends of the intelligence distribution were less likely to have sex. Higher intelligence was also associated with postponement of the initiation of the full range of partnered sexual activities. An expanded model incorporating a variety of control and mediator variables was tested to identify mechanisms by which the relationship operates. CONCLUSIONS Higher intelligence operates as a protective factor against early sexual activity during adolescence, and lower intelligence, to a point, is a risk factor. More systematic investigation of the implications of individual differences in cognitive abilities for sexual activities and of the processes that underlie those activities is warranted.

Assessing the Effects of the Dating Violence Prevention Program “Safe Dates” Using Random CoefficientRegression Modeling

The Safe Dates Project is a randomized trial for evaluating a school-based adolescent dating violence prevention program. Five waves of data were used to examine the effects of Safe Dates over time including primary and secondary prevention effects, moderators, and mediators of program effects. Using random coefficients models, with multiple imputation of missing data, significant program effects were found at all four follow-up periods on psychological, moderate physical, and sexual dating violence perpetration and moderate physical dating violence victimization. Marginal effects were found on sexual victimization. Effects on severe physical perpetration at all four follow-up periods were moderated by prior involvement in that type of violence. Primary and secondary prevention effects were found and the program was equally effective for males and females and for whites and non-whites. Program effects were mediated by changes in dating violence norms, gender-role norms, and awareness of community services.

Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)

Objective To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis. Design The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted. Setting One nursing home and six state mental hospitals in Minnesota, United States. Participants Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files. Interventions Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings. Main outcome measures Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy. Results The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline −13.8% v −1.0%; P<0.001). Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup. There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001). There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts. Systematic review identified five randomized controlled trials for inclusion (n=10 808). In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27). Conclusions Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.

Testosterone predicts initiation of coitus in adolescent females

Objective The purposes of this study were to demonstrate, using longitudinal data, that the pubertal rise in testosterone (T) is associated with subsequent increases in female sexual interest and activity, and to examine these relationships within the context of a social control variable. Methods Using data from a 2-year panel study of approximately 200 black and white postmenarcheal adolescent females, the relationships among semiannual measures of T, sex hormone binding globulin (SHBG), pubertal development, and self-reports of coital and noncoital sexual activity were assessed. Results Testosterone and changes in T were significantly related to the timing of subsequent transition to first coitus for blacks and whites. Frequency of attendance at religious services operated as a social control variable among white females, and was found to moderate T effects on sexual transition for this group. Conclusions These results are consistent with a biosocial model proposing T as a causal factor in female sexual activity, and suggest that biological effects are moderated by relevant social variables.

Risk and Protective Factors Distinguishing Profiles of Adolescent Peer and Dating Violence Perpetration

PURPOSE Violence profiles were created on the basis of whether adolescents used violence against both peers and dates, against dates but not peers, against peers but not dates, or against neither peers nor dates. We determined (1) whether risk and protective factors from five domains (individual attributes and behaviors, the peer, family, school, and neighborhood contexts), based primarily on social learning and social control theories, were associated with violence profiles, (2) whether factors distinguishing profiles varied by gender, and (3) which of the domains was most important in distinguishing profiles. METHODS Data are from adolescents in grades 8 through 10 from schools in three nonmetropolitan Counties (n = 2,907). RESULTS Adolescents who used violence against both peers and dates used more of each type of violence compared with those who used only one type of violence. They also had more maladaptive risk and protective scores than adolescents perpetrating only peer violence or neither type of violence, although they had few differences from those perpetrating only dating violence. Most social learning theory risk factors and social control theory protective factors distinguished the profiles as did psychological attributes and substance use. Factors distinguishing profile membership were generally the same for boys and girls, although some associations were stronger for boys than for girls. The model fit statistics suggest that the individual attributes and behaviors and the peer context models fit the data the best. CONCLUSIONS Suggestions for developing theoretically based interventions for preventing both peer and dating violence are presented.