Cumulative Marijuana Use and Carotid Intima-Media Thickness at Middle Age: The CARDIA Study

BackgroundLong-term cardiovascular health effects of marijuana are understudied. Future cardiovascular disease is often indicated by subclinical atherosclerosis for which carotid intima-media thickness is an established parameter.MethodsUsing the data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 Black and white women and men at Year 20 visit, we studied the association between carotid intima-media thickness in midlife and lifetime exposure to marijuana (1 marijuana year = 365 days of use) and tobacco smoking (1 pack-year = 20 cigarettes/day for 365 days). We measured carotid intima-media thickness by ultrasound and defined high carotid intima-media thickness at the threshold of the 75th percentile of all examined participants. We fit logistic regression models stratified by tobacco smoking exposure, adjusting for demographics, cardiovascular risk factors, and other drug exposures.ResultsData was complete for 3257 participants; 2722 (84%) reported ever marijuana use; 374 (11%) were current users; 1539 (47%) reported ever tobacco smoking; 610 (19%) were current smokers. Multivariable adjusted models showed no association between cumulative marijuana exposure and high carotid intima-media thickness in never or ever tobacco smokers, odds ratio (OR) 0.87 (95% confidence interval [CI]: 0.63-1.21) at 1 marijuana-year among never smokers and OR 1.11 (95% CI: 0.85-1.45) among ever tobacco smokers. Cumulative exposure to tobacco was strongly associated with high carotid intima-media thickness, OR 1.88 (95%CI: 1.20-2.94) for 20 pack-years of exposure.ConclusionsThis study adds to the growing body of evidence that there might be no association between the average population level of marijuana use and subclinical atherosclerosis.     

Telomerase, telomere length, and coronary artery calcium in black and white men in the CARDIA study

ObjectiveTo evaluate whether telomerase activity, measured in circulating blood leukocytes, might be associated with prevalent atherosclerosis, or predict future coronary artery disease risk.Methods and resultsWe examined associations of telomerase activity levels measured at year 15 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study with prevalent coronary artery calcium (CAC), progressive CAC at year 20, and incident CAC between years 15 and 20, in 440 black and white men aged 33–45 years. Telomere length was also measured in a subset of participants (N = 129).In multivariate-adjusted analysis, higher quartiles of telomerase were cross-sectionally associated with greater odds of prevalent CAC at year 15 (quartile 2: OR = 1.32, 95% CI: 0.54–3.23; quartile 3: OR = 1.40, 95% CI: 0.60–3.30; quartile 4: OR = 3.27, 95% CI: 1.39–7.71 compared with quartile 1, p-continuous = 0.012) and progressive CAC at year 20, but telomerase was not significantly associated with incidence of newly detectable CAC. Higher telomerase activity levels predicted greater CAC progression at year 20 among persons with short telomere length; low telomerase and short TL predicted less CAC progression.ConclusionTelomerase activity in leukocytes was associated with calcified atherosclerotic plaque, and was also a predictor of advancing plaque among persons with short telomeres.     

Nighttime blood pressure dipping in young adults and coronary artery calcium 10-15 years later: the coronary artery risk development in young adults study

Nighttime blood pressure (BP) dipping can be quantified as the ratio of mean nighttime (sleep) BP to mean daytime (awake) BP. People whose dipping ratio is ≥ 0.90 have been referred to as nondippers, and nondipping is associated with cardiovascular disease events. We examined the relationship between systolic nighttime BP dipping in young adults and the presence of coronary artery calcium (CAC) 10 to 15 years later using data from the ambulatory BP monitoring substudy of the Coronary Artery Risk Development in Young Adults Study. Among 239 participants with adequate measures of both nighttime and daytime readings and coronary artery calcium, the systolic BP dipping ratio ranged from 0.72 to 1.24 (mean, 0.88; SD, 0.06), and CAC was present 10 to 15 years later in 54 participants (22.6%). Compared with those whose systolic BP dipping ratio ranged from 0.88 to 0.92 (quartile 3), the 57 participants (23.9%) with less pronounced or absent dipping (ratio, 0.92-1.24; quartile 4) had an unadjusted odds ratio of 4.08 (95% CI, 1.48-11.2) for the presence of CAC. The 60 participants (25.1%) with a more pronounced dipping (ratio, 0.72-0.85; quartile 1) also had greater odds for presence of CAC (odds ratio, 4.76 [95% CI, 1.76-12.9]). When modeled as a continuous predictor, a U-shaped relationship between systolic BP dipping ratio and future CAC was apparent and persisted after adjustment for multiple potential confounders (P<0.001 for quadratic term). Both failure of systolic BP to dip sufficiently and "overdipping" during nighttime may be associated with future subclinical coronary atherosclerosis.     

<Emphasis Type="Italic">Tumor suppressor in lung cancer 1 (TSLC1)</Emphasis> alters tumorigenic growth properties and gene expression

Background  

Introduction of cDNA or genomic clones of the tumor suppressor in lung cancer 1 (TSLC1) gene into the non-small cell lung cancer line, A549, reverses tumorigenic growth properties of these cells. These results and the observation that TSLC1 is down-regulated in a number of tumors suggest that TSLC1 functions as a critical switch mediating repression of tumorigenesis.     

Current concepts in cheek reconstruction

For cutaneous cheek defects, the reconstructive surgeon should strive to optimize tissue match and scar camouflage while minimizing the distortion to neighboring facial landmarks. The surgeon must have an intimate understanding of the local anatomy and must be able to use the appropriate flap for the given characteristics of each defect and patient. Knowledge of several types of flaps and versatility in modifying these flaps from their "textbook" geometry are required. This article highlights an approach to local flap reconstruction with a review of flap modification for particular situations.     

Dietary restriction, mortality trajectories, risk and damage

Restriction of food intake extends lifespan in evolutionarily diverse organisms, including mammals. Dietary restriction (DR) also delays the appearance of ageing-related damage and pathology and keeps organisms in a youthful state for longer. DR has hence been suggested to lower the rate of ageing. Analysis of mortality rates can be used to test this idea. During ageing, mortality rates in general increase, approximately exponentially. Lifespan can be extended either by a reduction in the rate of increase in mortality rate with age or a lowering of the initial rate of mortality. A reduction in the slope of a mortality trajectory has generally been taken to indicate that the rate of ageing has been lowered. Data on the effects of temperature on mortality in Drosophila are in accordance with this idea. Lowered temperature extends lifespan solely by lowering the slope of the mortality trajectory and flies with a hotter thermal history have permanently elevated death rates. In contrast, lowering of the initial rate of mortality has been taken to leave the rate of ageing unaffected. In Drosophila and in mice, but not in rats, DR extends lifespan by lowering the initial mortality rate. In Drosophila, the effect of DR is acute, and mortality rate switches rapidly between DR and control values with the corresponding changes in nutritional regime. DR in Drosophila therefore has no impact upon the rate of ageing. Possible mechanisms by which DR can both delay damage and pathology and yet act acutely to determine mortality rates are discussed. In rodents, some phenotypes associated with DR, including microarray profiles, show rapid switching with changed nutritional regime, pointing to potentially acute effects of DR in mammals.