Jennifer O'Loughlin

A comprehensive view of sex-specific issues related to cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown.

Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials

Background: Many placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation. Methods: We searched the US Centers for Disease Control and Preventions Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention. Results: We identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible interval [CrI] 1.91–3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12–5.13), bupropion (OR 2.07, 95% CrI 1.73–2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69–2.62), nicotine tablet (OR 2.06, 95% CrI 1.12–5.13) and nicotine gum (OR 1.71, 95% CrI 1.35–2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95–5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09–4.08). Interpretation: Varenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.

Nicotine-dependence symptoms are associated with smoking frequency in adolescents

BACKGROUND Although many sociodemographic and psychosocial factors have been identified as related to adolescent smoking, few studies have examined the role of nicotine-dependence (ND) symptoms. The objective was to study the association between ND symptoms and smoking status among adolescents in the early stages of the smoking onset process. METHODS The McGill University Study on the Natural History of Nicotine Dependence is an ongoing 6-year prospective investigation of the natural history of ND among 1267 grade 7 students in ten Montreal high schools. The baseline response was 55.4%. Subjects for this cross-sectional analysis of baseline data, collected in 1999, included 241 past 3-month smokers (mean age [SD]=13.0+/-0.7 years at baseline). ND symptoms were measured in five indicators, including a measure based on the criteria for tobacco dependence in the International Classification of Diseases-10th Revision (ICD-10), the Hooked on Nicotine Checklist, and three symptom clusters (withdrawal, self-medication, and ND/cravings symptoms). The association between ND symptom indicators and each of sporadic, monthly, weekly, and daily smoking relative to less frequent smoking was investigated in multiple logistic regression analysis. RESULTS Despite low cigarette exposure, 16.6% (95% confidence interval [CI], 11.9%-21.3%) of past 3-month smokers were tobacco dependent. The proportion increased from 0%, 3.1% (95% CI, 0.0%-9.2%), and 4.6% (95% CI, 0.2%-9.0%) among triers, sporadic smokers, and monthly smokers, respectively, to 19.4% (95% CI, 5.5%-33.3%) and 65.9% (95% CI, 51.9%-79.9%) among weekly and daily smokers, respectively. ND/cravings consistently distinguished each smoking category from less frequent smokers; the odds ratios (95% CI) for ND/cravings symptoms were 1.16 (0.99-1.35) in sporadic smokers; 1.17 (1.06-1.29) in monthly smokers; 1.34 (1.19-1.50) in weekly smokers; and 1.39 (1.22-1.59) in daily smokers. CONCLUSIONS These data challenge current smoking onset models, which suggest that ND develops only after several years of heavy or daily smoking. ND symptoms are associated, at least cross-sectionally, with increased smoking in adolescents. To increase the likelihood of being effective, tobacco-control programs for children and adolescents will need to take early ND symptoms into account.

Do you see what I see? Weight status misperception and exposure to obesity among children and adolescents

Objective:Obesity prevention in childhood is important. However, changing childrens lifestyle behaviors to reduce overweight is a substantial challenge. Accurately perceiving oneself as overweight/obese has been linked to greater motivation to change lifestyle behaviors. Children and adolescents may be less likely to perceive themselves as overweight/obese if they are exposed to overweight/obese people in their immediate environments. This study examined whether youth who are exposed to overweight parents and schoolmates were more likely to misperceive their own weight status.Design:The Quebec Child and Adolescent Health and Social Survey was a provincially representative, school-based survey of children and adolescents conducted between January and May 1999.Subjects:3665 children and adolescents (age 9, n=1267; age 13, n=1186; age 16, n=1212) from 178 schools. Mean body mass index (BMI) was 17.5, 20.6 and 22.2 kg/m2, respectively.Measurements:The misperception score was calculated as the standardized difference between self-perception of weight status (Stunkard Body Rating Scale) and actual BMI (from measured height and weight). Exposure to obesity was based on parent and schoolmate BMI.Results:Overweight and obese youth were significantly more likely to misperceive their weight compared with non-overweight youth (P<0.001). Multilevel modeling indicated that greater parent and schoolmate BMI were significantly associated with greater misperception (underestimation) of weight status among children and adolescents.Conclusion:Children and adolescents who live in environments in which people they see on a daily basis, such as parents and schoolmates, are overweight/obese may develop inaccurate perceptions of what constitutes appropriate weight status. Targeting misperception may facilitate the adoption of healthy lifestyle behaviors and improve the effectiveness of obesity prevention interventions.

Insulin resistance syndrome in a representative sample of children and adolescents from Quebec, Canada

OBJECTIVES: To estimate the prevalence of insulin resistance syndrome (IRS) in a representative sample of youth. To test for the independent contribution of insulin resistance (IR) and adiposity to clustering of metabolic risk factors. To identify the underlying components of IRS. To examine the relationship between adiposity and fasting plasma levels of free fatty acids (FFA).METHODS: In 1999, we conducted a school-based survey of a representative sample of youth aged 9, 13 and 16 y in Quebec, Canada. Age-specific questionnaire data, standardized clinical measurements and a fasting blood sample were available for 2244 subjects. Fasting insulin and HOMA were used as surrogate measures of IR.RESULTS: In all age–sex groups, adiposity indices, blood pressure (BP), plasma glucose and triglycerides (TG) increased significantly with increasing insulin quartiles while HDL cholesterol (HDL-C) decreased. The overall prevalence of IRS defined as hyperinsulinaemia combined with two or more risk factors including overweight, high systolic BP, impaired fasting glucose, high TG and low HDL-C, was 11.5% (95% CI: 10.2–12.9). There were no significant differences in the prevalence of IRS across ages or between sexes. The independent contribution of adiposity to clustering of risk factors was stronger than that of fasting insulin (or HOMA-IR). Factor analysis revealed three factors (BMI/insulin/lipids, BMI/insulin/glucose and diastolic/systolic BP) consistent across ages suggesting that more than one pathophysiologic process underlies IRS. Although elevation of FFA might be in the causal pathway linking obesity to IR, we did not detect any consistent association between measures of fatness and fasting plasma FFA.CONCLUSION: IRS is highly prevalent in youth, even among children as young as age 9 y. Factor analysis identifies three physiologic domains within IRS with a unifying role for markers of IR and adiposity.

Determinants of First Puff and Daily Cigarette Smoking in Adolescents

Few prospective studies of smoking initiation have investigated a wide range of time-varying and invariant predictor variables at the individual and contextual levels concurrently. In this study (1999-2005), 877 Canadian students (mean age = 12.7 years) who had never smoked at baseline completed self-report questionnaires on cigarette smoking and 32 predictor variables in 20 survey cycles during secondary school. Height and weight were measured in survey cycles 1, 12, and 19. School administrators completed questionnaires on school tobacco control policies/activities, and trained observers collected data on access to tobacco products in commercial establishments near schools. Younger age, single-parent family status, smoking by parents, siblings, friends, and school staff, stress, impulsivity, lower self-esteem, feeling a need to smoke, not doing well at school, susceptibility to tobacco advertising, alcohol use, use of other tobacco products, and attending a smoking-tolerant school were independent determinants of smoking initiation. Independent determinants of daily smoking onset among initiators of nondaily smoking included smoking by siblings and friends, feeling a need to smoke, susceptibility to tobacco advertising, use of other tobacco products, and self-perceived mental and physical addiction. Adolescent tobacco control programs should address multiple individual and contextual-level risk factors. Strategies that address nicotine dependence symptoms are also needed for adolescents who have already initiated smoking.

A systematic review of longitudinal studies on the association between depression and smoking in adolescents

BackgroundIt is well-established that smoking and depression are associated in adolescents, but the temporal ordering of the association is subject to debate.MethodsLongitudinal studies in English language which reported the onset of smoking on depression in non clinical populations (age 13-19) published between January 1990 and July 2008 were selected from PubMed, OVID, and PsychInfo databases. Study characteristics were extracted. Meta-analytic pooling procedures with random effects were used.ResultsFifteen studies were retained for analysis. The pooled estimate for smoking predicting depression in 6 studies was 1.73 (95% CI: 1.32, 2.40; p < 0.001). The pooled estimate for depression predicting smoking in 12 studies was 1.41 (95% CI: 1.21, 1.63; p < 0.001). Studies that used clinical measures of depression were more likely to report a bidirectional effect, with a stronger effect of depression predicting smoking.ConclusionEvidence from longitudinal studies suggests that the association between smoking and depression is bidirectional. To better estimate these effects, future research should consider the potential utility of: (a) shorter intervals between surveys with longer follow-up time, (b) more accurate measurement of depression, and (c) adequate control of confounding.

Plasma PCSK9 Is Associated with Age, Sex, and Multiple Metabolic Markers in a Population-Based Sample of Children and Adolescents

BACKGROUND Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein convertase that posttranslationally promotes the degradation of the low-density lipoprotein receptor (LDLR) in hepatocytes and increases plasma LDL cholesterol (LDL-C). Heterozygote gain-of-function mutations of PCSK9 are associated with the familial hypercholesterolemia phenotype, whereas loss-of-function variants are associated with reduced LDL-C concentrations and lower coronary risk. Plasma PCSK9 correlates with body mass index, triglyceridemia, total cholesterol, and LDL-C in adults, but no data are available in youth. METHODS We studied 1739 French Canadian youth ages 9, 13, and 16 years who participated in the Quebec Child and Adolescent Health and Social Survey, a province-wide school-based survey conducted in 1999. An ELISA assay was used to measure plasma PSCK9. RESULTS The mean (SD) plasma PCSK9 concentration was 84.7 (24.7) microg/L in the sample. In boys, plasma PCSK9 decreased with age, whereas the inverse was true for girls. There were statistically significant positive associations between PCSK9 and fasting glucose, insulin, and HOMA-IR (homeostasis model assessment of insulin resistance). In multivariable analysis, a 10% higher fasting insulin was associated with a 1%-2% higher PCSK9 in both sexes. There were also positive associations between PCSK9 and total cholesterol, LDL-C, and triglycerides, as well as with HDL-C and apolipoproteins A1 and B. CONCLUSIONS PCSK9 is associated with age, sex, and multiple metabolic markers in youth. A novel finding is that PCSK9 is associated with fasting insulinemia, which suggests that PCSK9 could play a role in the development of dyslipidemia associated with the metabolic syndrome. .

Influence of weather conditions and season on physical activity in adolescents.

PURPOSE Little is known about how seasonal variation in physical activity relates to declining physical activity in adolescence. We quantified how each of daily weather conditions and season affect physical activity during adolescence. METHODS We followed 1293 students, initially aged 12 to 13 years over 5 years. Participants completed a 7-day physical activity recall checklist every 3 months. Data on daily weather conditions were obtained from Environment Canada. The association between the number of physical activity sessions per day, and each of season, and daily weather conditions was assessed in Poisson regressions. RESULTS Adjusting for age, sex, and month, the average number of physical activity sessions per day was 2% to 4% lower for every 10 mm of rainfall and 1% to 2% higher for every 10 degrees C increase in temperature. Although every 10 cm of snow accumulation was associated with 5% higher activity rates, days with snowfall had lower physical activity. Physical activity was lower during winter and increased during warmer months. However, the warm-month increases did not compensate for winter decreases so that activity decreased by 7% yearly. CONCLUSIONS Declines in physical activity during adolescence may be partly explained by declines during winter. Increasing opportunities for physical activity during poor weather, in particular during winter, may mitigate declines in physical activity during adolescence.

Prevalence and Correlates of Physical Activity Behaviors among Elementary Schoolchildren in Multiethnic, Low Income, Inner-City Neighborhoods in Montreal, Canada

PURPOSE To describe the prevalence and correlates of physical inactivity and of participation in organized sports at and outside school among elementary schoolchildren in multiethnic, low income, urban neighborhoods in Montreal, Canada. METHODS As part of the evaluation of a school-based heart health promotion program, baseline data on physical activity behaviors and potential correlates of these behaviors, were collected from 2285 students aged 9-13 in all 130 grade 4 to 6 classes in 24 inner-city elementary schools from May to June 1993. RESULTS One-fifth of boys (20.5%) and 24.4% of girls were inactive; 40.0% and 33.3% of boys and girls respectively, participated in school sports teams; 82.5% and 74.7% participated in organized sports outside school. Declines in activity levels with age were apparent in both genders. Children who participated in organized sports programs at and outside school, those with higher perceived self-efficacy for physical activity, and those with more parental support for engaging in physical activity were more active. Children of Asian family origin were less active. Socioeconomic status was related to participation in organized sports outside school. CONCLUSIONS To reach children in socio-economically disadvantaged areas and to prevent age-related declines in activity levels, interventions promoting physical activity should focus on increasing availability and access to community-based organized sports programs at and outside school. Also they should include components to increase parental support and to improve perceived self-efficacy for physical activity.