Hemodynamics of increased pulse pressure in older women in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study

Pulse pressure increases with advancing age particularly in women. As a result, women have a higher pulse pressure than men from midlife onward. Higher pulse pressure in older women as compared to men is often attributed to increased aortic wall stiffness and premature wave reflection. To evaluate this hypothesis, we measured central aortic input impedance, pulse wave velocity, and wave reflection in 408 older men and women (age range, 69 to 94 yr, mean 75 yr) participating in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik). Women as compared to men had higher pulse pressure (75.8+/-18.7 versus 69.5+/-16.8 mm Hg, P<0.001) and smaller aortic diameters (2.74+/-0.24 versus 2.97+/-0.28 cm, P<0.001). Augmentation index (AI) was higher (11.0+/-15.9 versus 7.9+/-12.9%, P=0.032) in women whereas proximal aortic elastance-wall thickness product (Eh) did not differ (P=0.61). In a stepwise model for pulse pressure that included age and sex and offered aortic diameter, Eh, mean pressure, AI, pulse wave velocity, height, weight, and body surface area as additional covariates, higher pulse pressure was associated with increased wall stiffness, smaller aortic diameter, higher mean pressure, and increased AI (Model R(2)=0.59, P<0.001). The sex difference in pulse pressure (6.6+/-1.7 mm Hg, P<0.001) persisted after Eh entered the model (6.9+/-1.5 mm Hg, P<0.001) but not after aortic diameter entered the model (-0.4+/-1.4 mm Hg, P=0.75). Thus, reduced aortic diameter and impaired matching between diameter and flow accounts for the sex difference in pulse pressure in an unselected community-based cohort of older people.     

Making Sense of Intratumor Genetic Heterogeneity: Altered Frequency of Androgen Receptor CAG Repeat Length Variants in Breast Cancer Tissues

To examine the significance of intratumor genetic heterogeneity (ITGH) of the androgen receptor (AR) gene in breast cancer, patient‐matched samples of laser capture microdissected breast tumor cells, adjacent normal breast epithelia cells, and peripheral blood leukocytes were sequenced using a novel next generation sequencing protocol. This protocol measured the frequency of distribution of a variable AR CAG repeat length, a functional polymorphism associated with breast cancer risk. All samples exhibited some degree of ITGH with up to 30 CAG repeat length variants identified. Each type of tissue exhibited a different distribution profile of CAG repeat lengths with substantial differences in the frequencies of zero and 18–25 CAG AR variants. Tissue differences in the frequency of ARs with each of these CAG repeat lengths were significant as measured by paired, twin t‐tests. These results suggest that preferential selection of 18–25 CAG repeat length variants in breast tumors may be associated with breast cancer, and support the observation that shorter CAG repeats may protect against breast cancer. They also suggest that merely identifying variant genes will be insufficient to determine the critical mutational events of oncogenesis, which will require measuring the frequency of distribution of mutations within cancerous and matching normal tissues.     

Mediation Analysis of Aortic Stiffness and Renal Microvascular Function

Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular–microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72–92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=−2.28±0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, −1.35 to −0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, −2.22 to −0.40; 95% confidence interval of indirect effect including renal vascular resistance, −2.51 to −0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.     

Neurological examination findings to predict limitations in mobility and falls in older persons without a history of neurological disease

PURPOSE: To estimate the prevalence of neurological signs and their association with limitations in mobility and falls in a sample of older persons without known neurological disease. METHODS: A neurologist examined 818 participants from the InCHIANTI study who were aged > or =65 years and who did not have cognitive impairment, treatment with neuroleptics, and a history of neurological disease. Mobility was assessed as walking speed and self-reported ability to walk at least 1 km without difficulty. Participants were asked to report falls that had occurred in the previous 12 months. RESULTS: Less than 20% (160/818) of participants had no neurological signs. Neurological signs were more prevalent in older participants and those with impaired mobility. When all neurological signs were included in sex-and age-adjusted multivariate models, 10 were mutually independent correlates of poor mobility. After adjusting for age and sex, the number of neurological signs was associated with progressively slower walking speed (P <0.001), a higher probability of reported inability to walk 1 km (P <0.001), and a history of falls (P <0.05). CONCLUSION: Neurological signs are independent correlates of limitations in mobility and falls in older persons who have no clear history of neurological disease.     

A TGF-beta1 polymorphism association with dementia and neuropathologies: the HAAS

The transforming growth factor-beta1 (TGF-beta1) is involved in post-ischemic neuronal rescue and in beta-amyloid turn-over. We hypothesized that the risk for dementia and related neuropathologies is modified by the TGF-beta1 functional genetic variants. The association of the TGF-beta1+29T-->C polymorphism with dementia was examined in a sample of 261 cases and 491 controls from the Honolulu-Asia Aging Study, including 282 subjects with autopsy data. Dementia was assessed in 1991 and 1994 by a multi-step protocol and standardized diagnostic criteria. The analysis was adjusted for demographic and vascular factors. Compared to the TT genotype, the TC and the CC genotypes were associated with a reduced risk for vascular dementia (OR(TC)=0.28, 95% confidence interval (CI): 0.1-0.9; OR(CC)=0.28, CI: 0.1-0.9), microinfarcts (OR(CC)=0.31, CI: 0.13-0.71) and cerebral amyloid angiopathy (OR(CC)=0.48, CI: 0.2-0.9). The CC genotype was associated with an increase risk of neocortical plaques (OR(CC)=4.34, CI: 1.6-11.8). These preliminary data suggest that the TGF genetic variability may be important in the risk of vascular related dementia.     

Treatment efficacy of social communication skills training after traumatic brain injury: a randomized treatment and deferred treatment controlled trial

Dahlberg CA, Cusick CP, Hawley LA, Newman JK, Morey CE. Harrison-Felix CL, Whiteneck GG. Treatment efficacy of social communication skills training after traumatic brain injury: a randomized treatment and deferred treatment controlled trial.

Objective

To evaluate the efficacy of a replicable group treatment program to improve social communication skills after traumatic brain injury (TBI).

Design

Randomized treatment and deferred treatment controlled trial, with follow-up at 3, 6, and 9 months post-treatment.

Setting

Community.

Participants

Volunteer sample of 52 people with TBI who were at least 1 year postinjury, who received rehabilitation, and who had identified social communication deficits.

Intervention

Twelve weekly group sessions (1.5h each) to improve social communication.

Main Outcome Measures

The Profile of Functional Impairment in Communication (PFIC), Social Communication Skills Questionnaire–Adapted (SCSQ-A), Goal Attainment Scale (GAS), Craig Handicap Assessment and Reporting Technique–Short Form social integration and occupation subscales, Community Integration Questionnaire social integration and productivity subscales, and Satisfaction With Life Scale (SWLS).

Results

Independent samples t test analysis showed significant treatment effect compared with no treatment on 7 of 10 of the PFIC subscales (P range, .024 to <.001) and the SCSQ-A (P=.005) after the first 12 weeks of the study. After 12 weeks of treatment for all participants, repeated-measures analysis showed significant improvements from baseline on 9 of 10 PFIC subscales (P range, .01−.001), SCSQ-A (P≤.001), GAS (P≤.001), and SWLS (P=.011). At 6-month follow-up, scores were significantly better than baseline on 6 of 10 PFIC scales (P range, .01−.001), the SCSQ-A (P≤.001), GAS (P≤.001), and SWLS (P≤.001).

Conclusions

TBI subjects who received social communication skills training had improved communication skills that were maintained on follow-up. Overall life satisfaction for participants was improved.     

Progressive aortic valve inflammation occurring despite apparent remission of relapsing polychondritis

We describe a patient with relapsing polychondritis in whom aortic valve inflammation developed 3 years after diagnosis, when the polychondritis had been in apparent remission for an extended period of time. Infection and cardiac involvement can be significant complications of relapsing polychondritis. Recommendations for monitoring and treatment of patients with this disease are discussed.