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Asymptomatic peripheral arterial disease is associated with more adverse lower extremity characteristics than intermittent claudication.

MM McDermott — 2008-06-23T20:16:05-00:00

Circulation, Vol. 117, No. 19. (13 May 2008), pp. 2484-2491.

BACKGROUND: This study assessed functional performance, calf muscle characteristics, peripheral nerve function, and quality of life in asymptomatic persons with peripheral arterial disease (PAD). METHODS AND RESULTS: PAD participants (n=465) had an ankle brachial index <0.90. Non-PAD participants (n=292) had an ankle brachial index of 0.90 to 1.30. PAD participants were categorized into leg symptom groups including intermittent claudication (n=215) and always asymptomatic (participants who never experienced exertional leg pain, even during the 6-minute walk; n=72). Calf muscle was measured with computed tomography. Analyses were adjusted for age, sex, race, ankle brachial index, comorbidities, and other confounders. Compared with participants with intermittent claudication, always asymptomatic PAD participants had smaller calf muscle area (4935 versus 5592 mm(2); P<0.001), higher calf muscle percent fat (16.10% versus 9.45%; P<0.001), poorer 6-minute walk performance (966 versus 1129 ft; P=0.0002), slower usual-paced walking speed (P=0.0019), slower fast-paced walking speed (P<0.001), and a poorer Short-Form 36 Physical Functioning score (P=0.016). Compared with an age-matched, sedentary, non-PAD cohort, always asymptomatic PAD participants had smaller calf muscle area (5061 versus 5895 mm(2); P=0.009), poorer 6-minute walk performance (1126 versus 1452 ft; P<0.001), and poorer Walking Impairment Questionnaire speed scores (40.87 versus 57.78; P=0.001). CONCLUSIONS: Persons with PAD who never experience exertional leg symptoms have poorer functional performance, poorer quality of life, and more adverse calf muscle characteristics compared with persons with intermittent claudication and a sedentary, asymptomatic, age-matched group of non-PAD persons.

Elevated levels of inflammation, d-dimer, and homocysteine are associated with adverse calf muscle characteristics and reduced calf strength in peripheral arterial disease.

MM McDermott — 2008-06-21T01:23:00-00:00

Journal of the American College of Cardiology, Vol. 50, No. 9. (28 August 2007), pp. 897-905.

OBJECTIVES: This study determined whether increased levels of inflammatory blood markers, D-dimer, and homocysteine were associated with smaller calf skeletal muscle area, increased calf muscle percent fat, reduced calf muscle density, and poorer calf strength in persons with lower extremity peripheral arterial disease (PAD). BACKGROUND: Elevated levels of inflammatory markers and D-dimer are associated with greater functional impairment and functional decline in persons with PAD. Mechanisms of these associations are unknown. METHODS: Participants were 423 persons with PAD. Calf muscle area, percent fat, and density were measured with computed tomography. Physical activity levels were measured objectively over 7 days with the Caltrac (Muscle Dynamics Fitness Network, Inc., Rocklin, California) vertical accelerometer. Isometric plantarflexion strength was measured. Analyses were adjusted for age, gender, race, comorbidities, the ankle-brachial index, and other potential confounders. RESULTS: Higher levels of D-dimer (p = 0.014), C-reactive protein (CRP) (p = 0.002), interleukin (IL)-6 (p < 0.001), and soluble vascular cellular adhesion molecule (sVCAM)-1 (p = 0.008) were associated with smaller calf muscle area. Higher sVCAM-1 (p = 0.004) and IL-6 (p = 0.017) were associated with higher calf muscle percent fat. Higher D-dimer (p < 0.001), sVCAM-1 (p < 0.001), and homocysteine (p = 0.014) were associated with lower calf muscle density. These associations were generally unchanged after additional adjustment for physical activity. Higher sVCAM-1 (p = 0.013) was associated with lower calf strength. CONCLUSIONS: These data show, for the first time, that higher levels of inflammation, D-dimer, and homocysteine are associated with more adverse calf muscle characteristics in persons with PAD. These associations may contribute to previously established associations between elevated biomarkers and functional impairment and functional decline in PAD.

Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association

Thomas Pearson — 2008-05-17T01:42:04-00:00

Circulation, Vol. 107, No. 3. (28 January 2003), pp. 499-511.

10.1161/01.CIR.0000052939.59093.45

Reduction in Blood Pressure With Statins: Results From the UCSD Statin Study, a Randomized Trial.

BA Golomb — 2008-04-29T20:42:00-00:00

Archives of internal medicine, Vol. 168, No. 7. (14 April 2008), pp. 721-727.

BACKGROUND: Some studies have suggested reductions in blood pressure (BP)with statin treatment, particularly in persons with hypertension. Randomized trial evidence is limited. METHODS: We performed a randomized, double-blind, placebo-controlled trial with equal allocation to simvastatin, 20 mg; pravastatin sodium,40 mg; or placebo for 6 months. Nine hundred seventy-three men and women without known cardiovascular disease or diabetes mellitus, with low-density lipoprotein cholesterol screening levels of 115 to 190mg/dL, had assessment of systolic and diastolic BP (SBP and DBP, respectively). Blood pressure values were compared for placebo vs statins by intention-to-treat (ITT) analysis. Additional analyses were performed that (1) were confined to subjects with neither high baseline BP (SBP >140 mm Hg or DBP >90mm Hg) nor receiving BP medications, to exclude groups in whom BP medications or medication changes may have influenced results, and (2) separately evaluated simvastatin and pravastatin (vs placebo). The time course of BP changes after statin initiation and the effect of stopping statins on BP were examined. RESULTS: Statins modestly but significantly reduced BP relative to placebo,by 2.2 mm Hg for SBP (P = .02) and 2.4mm Hg for DBP (P < .001) in ITT analysis.Blood pressure reductions ranged from 2.4 to 2.8 mm Hg for both SBP and DBP with both simvastatin and pravastatin, in those subjects with full follow-up, and without potential for influence by BP medications (ie, neither receiving nor meriting BP medications). CONCLUSIONS: Reductions in SBP and DBP occurred with hydrophilic and lipophilic statins and extended to normotensive subjects. These modest effects may contribute to the reduced risk of stroke and cardiovascular events reported on statins. Trial Registration clinicaltrials.gov Identifier: NCT00330980.

Psychosocial and behavioral predictors of longevity: The aging and death of the "termites"

HS Friedman — 2008-03-08T15:21:01-00:00

American Psychologist, Vol. 50, No. 2. (1995), pp. 69-78.

Impulsive, undercontrolled personalities and major family stresses are known predictors of impaired adjustment, but long-term health effects are unclear. In an archival prospective cohort design, we followed up on L. M. Terman's (Terman & Oden, 1947) sample of gifted children by collecting and coding death certificates for the half of the sample that is now dead. Statistical survival analyses were used to predict longevity and cause of death as a function of parental divorce during childhood, unstable marriage patterns in adulthood, childhood personality, adult adjustment, and possible mediating health behaviors. Psychosocial factors emerged as important risks for premature mortality.

Childhood conscientiousness and longevity: health behaviors and cause of death.

HS Friedman — 2008-01-21T15:11:13-00:00

Journal of Personality and Social Psychology, Vol. 68, No. 4. (1995), pp. 696-703.

Previous research showed that conscientiousness (social dependability) in childhood predicted longevity in an archival prospective cohort study of bright children first studied by Terman in the 1920s (H. S. Friedman et al., 1993). Possible behavioral mechanisms for this robust association are now examined by gathering cause of death information and by considering the possible mediating influences of drinking alcohol, smoking, and overeating. Survival analyses (N = 1,215) suggest that the protective effect of conscientiousness is not primarily due to accident avoidance and cannot be mostly explained by abstinence from unhealthy substance intake. Conscientiousness may have more wide-ranging effects on health-relevant activities.

Sociodemographic and psychosocial factors in childhood as predictors of adult mortality

JE Schwartz — 2008-01-21T15:11:11-00:00

American Journal of Public Health, Vol. 85, No. 9. (1995), pp. 1237-1245.

Objectives. Childhood sociodemographic, psychosocial, and environmental factors are often assumed to affect adult health and longevity. These relationships were prospectively tested by using the 7-decade Terman Life Cycle Study of Children With High Ability (n = 1285). Methods. Parental socioeconomic status, childhood health, objective childhood stressors (e.g., death or divorce of parents), and childhood personality were considered as potential predictors in hazard regression analyses of longevity through 1991. Results. Parental divorce during childhood predicted decreased longevity, with sex controlled. Other potential social predictors failed to show significant associations with longevity. Three dimensions of childhood personality-conscientiousness, lack of cheerfulness, and permanency of mood (males only)-predicted increased longevity. The effects of parental divorce and childhood personality were largely independent and did not account for any of the gender difference in mortality. Conclusions. A small number of childhood factors significantly predicted mortality across the life span in this sample. Further research should focus on how these psychosocial factors influence longevity.

Does childhood personality predict longevity?

HS Friedman — 2008-01-21T15:11:10-00:00

Journal of Personality and Social Psychology, Vol. 65, No. 1. (1993), pp. 176-185.

Key models relating personality and health predict that personality in childhood is indicative of later health and longevity. Longevity predictions are tested using data derived from the 7-decade longitudinal study initiated by L. M. Terman 1921 (L. M. Terman & M. H. Oden, 1947). Variables representing major dimensions of personality are used in statistical survival analyses of longevity in 1,178 males and females. Conscientiousness in childhood was clearly related to survival in middle to old age. This finding (a) establishes that childhood personality is related to survival decades into the future, (b) confirms the validity of the conscientiousness dimension in conceptualizing personality, and (c) points to likely and unlikely pathways linking personality to health. Contrary to expectation, cheerfulness (optimism and sense of humor) was inversely related to longevity, suggesting a possible need for reconceptualization of its health relevance.

A Life Course Perspective on Childhood Cheerfulness and its Relation to Mortality Risk

Leslie Martin — 2007-11-08T12:20:01-00:00

Pers Soc Psychol Bull, Vol. 28, No. 9. (1 September 2002), pp. 1155-1165.

Under some conditions, cheerfulness promotes health, but cheerfulness also has been associated with unfavorable health outcomes. This study follows up the inverse relation between childhood cheerfulness and longevity found among 1,215 men and women first assessed as children by Lewis Terman in 1922. Risky hobbies, smoking, drinking, and obesity, as well as cause of death, are examined, along with adulthood personality and adjustment. Several hypotheses about mediating variables can be eliminated by these analyses; these data do hint, however, that cheerful children grow up to be more careless about their health. Although correlational and survival analyses suggest that health behaviors play a role, they are unable to explain the observed cheerfulness-mortality link, thus supporting the idea that cheerfulness is multifaceted and should not be assumed to be related to health in a simple manner. 10.1177/01461672022812001

The fallacy of employing standardized regression coefficients and correlations as measures of effect.

S Greenland — 2005-10-24T17:05:53-00:00

Am J Epidemiol, Vol. 123, No. 2. (February 1986), pp. 203-208.

Cell cycle -dependent proteolysis in plants. Identification Of the destruction box pathway and metaphase arrest produced by the proteasome inhibitor mg132

P Genschik — 2005-06-23T13:29:22-00:00

Plant Cell, Vol. 10, No. 12. (December 1998), pp. 2063-2076.

It is widely assumed that mitotic cyclins are rapidly degraded during anaphase, leading to the inactivation of the cell cycle-dependent protein kinase Cdc2 and allowing exit from mitosis. The proteolysis of mitotic cyclins is ubiquitin/26S proteasome mediated and requires the presence of the destruction box motif at the N terminus of the proteins. As a first attempt to study cyclin proteolysis during the plant cell cycle, we investigated the stability of fusion proteins in which the N-terminal domains of an A-type and a B-type tobacco mitotic cyclin were fused in frame with the chloramphenicol acetyltransferase (CAT ) reporter gene and constitutively expressed in transformed tobacco BY2 cells. For both cyclin types, the N-terminal domains led the chimeric cyclin-CAT fusion proteins to oscillate in a cell cycle-specific manner. Mutations within the destruction box abolished cell cycle-specific proteolysis. Although both fusion proteins were degraded after metaphase, cyclin A-CAT proteolysis was turned off during S phase, whereas that of cyclin B-CAT was turned off only during the late G2 phase. Thus, we demonstrated that mitotic cyclins in plants are subjected to post-translational control (e.g., proteolysis). Moreover, we showed that the proteasome inhibitor MG132 blocks BY2 cells during metaphase in a reversible way. During this mitotic arrest, both cyclin-CAT fusion proteins remained stable.