Trends in mortality from coronary heart and cerebrovascular disease in Switzerland, 1969-87.

Trends in age-specific and age-standardized death certification rates from all ischaemic heart disease and cerebrovascular disease in Switzerland have been analysed for the period 1969-87, i.e. since the introduction of the Eighth Revision of the International Classification of Diseases for coding causes of death. For coronary heart disease, overall age-standardized rates of males in the mid-late 1980's were similar to those in the late 1960's, although some upward trend was evident up to the mid 1970's (with a peak rate of 120.4/100,000, World standard, in 1978) followed by steady declines in more recent years (103.8/100,000 in 1987). These falls were larger in truncated (35 to 64 years) rates. For females, overall age-standardized rates were stable around a value of 40/100,000, while truncated rates tended to decrease, particularly over most recent years, with an overall decline of over 25%. Examination of age-specific trends showed that in both sexes declines at younger ages were already evident in the earlier calendar period, while above age 50 some fall became evident only in most recent years. Thus, in a formal log-linear age/period/cohort model, both a period and a cohort component emerged. In relation to cerebrovascular diseases, the overall declines were around 40% in males (from 67.4 to 41.2/100,000, World standard) and 45% for females (from 56.6 to 31.7/100,000), and were proportionally comparable across subsequent age groups above age 45. The estimates for the age/period/cohort model were thus downwards both for the period and the cohort component although, in such a situation, it is difficult to disentangle the major underlying component.(ABSTRACT TRUNCATED AT 250 WORDS)

Prescription footwear for severe injuries of foot and ankle: effect on regularity and symmetry of the gait assessed by trunk accelerometry.

After foot and/or ankle fracture, the restoration of optimal gait symmetry is one of the criteria of recovery. Orthotic insoles and orthopaedic shoes improve gait symmetry and regularity by controlling joint motion and improving alignment. The aim of the present study was to assess the effect of prescription footwear on gait quality by using accelerometers attached to the lower back. Sixteen adult patients with persistent disability after ankle and/or foot fractures performed two 30-s walking trials with and without prescription footwear (insoles and stabilizing shoes). Sixteen control subjects were also tested for comparison. The autocorrelation function was computed from the acceleration signal and the first two dominant periods were assessed (d1 and d2). Two parameters were used: (1) Stride Regularity (SR) which expresses the similarity between strides over time (d2), and (2) Stride Symmetry (SS) a ratio (d1/d2) which expresses the left/right similarity of gait independently of repeatability in the successive movements of each limb. In control subjects, SR and SS were 0.86+/-0.05 (correlation coefficient) and 81+/-10%, respectively. In the patient group, the effect of footwear was significant (SR: 0.88+/-0.06 vs. 0.90+/-0.05, SS: 38+/-23% vs. 46+/-27%). Pain was also significantly reduced (-34%). By using a rapid and low-cost method, we objectively quantified gait quality improvement after footwear intervention, concomitant to pain reduction. Substantial inter-patient variability in the footwear outcome was observed. In conclusion, we believe that trunk accelerometry can be a useful tool in the field of gait rehabilitation.

Dominant TNF-α(+) Mycobacterium tuberculosis-specific CD4(+) T cell responses discriminate between latent infection and active disease.

Rapid diagnosis of active Mycobacterium tuberculosis (Mtb) infection remains a clinical and laboratory challenge. We have analyzed the cytokine profile (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2)) of Mtb-specific T cells by polychromatic flow cytometry. We studied Mtb-specific CD4(+) T cell responses in subjects with latent Mtb infection and active tuberculosis disease. The results showed substantial increase in the proportion of single-positive TNF-α Mtb-specific CD4(+) T cells in subjects with active disease, and this parameter was the strongest predictor of diagnosis of active disease versus latent infection. We validated the use of this parameter in a cohort of 101 subjects with tuberculosis diagnosis unknown to the investigator. The sensitivity and specificity of the flow cytometry-based assay were 67% and 92%, respectively, the positive predictive value was 80% and the negative predictive value was 92.4%. Therefore, the proportion of single-positive TNF-α Mtb-specific CD4(+) T cells is a new tool for the rapid diagnosis of active tuberculosis disease.

Assessing the associations between mental disorders, cardiovascular risk factors, and cardiovascular disease : the CoLaus/PsyCoLaus study

Background: Cardio-vascular diseases (CVD), their well established risk factors (CVRF) and mental disorders are common and co-occur more frequently than would be expected by chance. However, the pathogenic mechanisms and course determinants of both CVD and mental disorders have only been partially identified.Methods/Design: Comprehensive follow-up of CVRF and CVD with a psychiatric exam in all subjects who participated in the baseline cross-sectional CoLaus study (2003-2006) (n=6'738) which also included a comprehensive genetic assessment. The somatic investigation will include a shortened questionnaire on CVRF, CV events and new CVD since baseline and measurements of the same clinical and biological variables as at baseline. In addition, pro-inflammatory markers, persistent pain and sleep patterns and disorders will be assessed. In the case of a new CV event, detailed information will be abstracted from medical records. Similarly, data on the cause of death will be collected from the Swiss National Death Registry. The comprehensive psychiatric investigation of the CoLaus/PsyCoLaus study will use contemporary epidemiological methods including semi-structured diagnostic interviews, experienced clinical interviewers, standardized diagnostic criteria including threshold according to DSM-IV and sub-threshold syndromes and supplementary information on risk and protective factors for disorders. In addition, screening for objective cognitive impairment will be performed in participants older than 65 years.Discussion: The combined CoLaus/PsyCoLaus sample provides a unique opportunity to obtain prospective data on the interplay between CVRF/CVD and mental disorders, overcoming limitations of previous research by bringing together a comprehensive investigation of both CVRF and mental disorders as well as a large number of biological variables and a genome-wide genetic assessment in participants recruited from the general population.

Adhésion thérapeutique et maladies chroniques: l'exemple de l'ostéoporose [Adherence and chronic disease: what's about osteoporosis].

Osteoporosis is a silent chronic disease. The human, medical and economic impacts, as well as the easy access to the screening and specific treatments incite us to introduce a treatment as soon as this one is justified. The maximal efficiency of treatments is possible only if the therapeutic adherence (which includes compliance and persistence) is good. Regrettably, as frequently in the chronic diseases, this one is often bad. It can be strengthened by a better patient's education and information, a better follow-up, but also by a today available variety of treatments.

Segmentation of foot and ankle complex based on kinematic criteria.

Although various foot models were proposed for kinematics assessment using skin makers, no objective justification exists for the foot segmentations. This study proposed objective kinematic criteria to define which foot joints are relevant (dominant) in skin markers assessments. Among the studied joints, shank-hindfoot, hindfoot-midfoot and medial-lateral forefoot joints were found to have larger mobility than flexibility of their neighbour bonesets. The amplitude and pattern consistency of these joint angles confirmed their dominancy. Nevertheless, the consistency of the medial-lateral forefoot joint amplitude was lower. These three joints also showed acceptable sensibility to experimental errors which supported their dominancy. This study concluded that to be reliable for assessments using skin markers, the foot and ankle complex could be divided into shank, hindfoot, medial forefoot, lateral forefoot and toes. Kinematics of foot models with more segments must be more cautiously used.

Mycobacterium tuberculosis-specific CD8 T cells are functionally and phenotypically different between latent infection and active disease

Purpose/Objective: Tuberculosis (TB) is the second worldwide leading cause of death from an infectious disease after HIV infection. Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8 T-cells is controversial. We performed comprehensive functional and phenotypic characterizations of Mtb-specific CD8 T-cell responses in 273 subjects with either latent Mtb infection (LTBI) or active TB disease (TB) to assess their profile and relevance in TB. Materials and methods: Using multi-parametric flow cytometry, we assessed Mtb-specific CD8 T-cell functional (production of IFNgamma, IL-2 and TNF-alpha; proliferation capacity and cytotoxicity) and phenotypic (T-cell differentiation and exhaustion) profiles in cells isolated from peripheral blood and correlated these profiles with distinct clinical presentations. Results: Mtb-specific CD8 T-cells were detected in most TB patients and few LTBI subjects (65% and 15%, respectively; P < 0.00001) and were of similar magnitude with a comparable cytokines profile (IFNg+TNFa+IL2-) in both groups. Mtb-specific CD8 T-cells were mostly TEMRA (CD45RA+ CCR7-) co-expressing 2B4 and CD160 in LTBI subjects and mostly TEM (CD45RA-CCR7-) lacking PD-1/ CD160/2B4 in TB patients. Furthermore, Mtb-specific CD8 T-cells mostly expressed very little perforin and granulysin but contained granzymes A and B or lacked all these cytotoxic markers in TB and LTBI subjects, respectively. However, in vitro expanded Mtb-specific CD8 T-cells acquired perforin, granulysin and granzymes. Finally, Mtb-specific CD8 T-cell responses were more robust and prone to proliferate in patients with extrapulmonary compared to pulmonary TB. Conclusions: The clinical status and TB presentation are associated to specific profiles of Mtb-specific CD8 T-cell responses, thus indicating distinct dynamics between the mycobacteria, the CD8 T-cell response and the clinical outcome. Our data shed light on the controversial reached by studies performed in human and animal models, thus advancing the current knowledge on the complex dynamic of TB immunity.

Overlap Between Common Genetic Polymorphisms Underpinning Kidney Traits and Cardiovascular Disease Phenotypes: The CKDGen Consortium.

BACKGROUND: Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits. STUDY DESIGN: We conducted 2 targeted analyses. First, we examined whether known single-nucleotide polymorphisms (SNPs) underpinning kidney traits were associated with a series of vascular phenotypes. Additionally, we tested whether vascular SNPs were associated with markers of kidney damage. Significance was set to 1.5×10(-4) (0.05/325 tests). SETTING & PARTICIPANTS: Vascular outcomes were analyzed in participants from the AortaGen (20,634), CARDIoGRAM (86,995), CHARGE Eye (15,358), CHARGE IMT (31,181), ICBP (69,395), and NeuroCHARGE (12,385) consortia. Tests for kidney outcomes were conducted in up to 67,093 participants from the CKDGen consortium. PREDICTOR: We used 19 kidney SNPs and 64 vascular SNPs. OUTCOMES & MEASUREMENTS: Vascular outcomes tested were blood pressure, coronary artery disease, carotid intima-media thickness, pulse wave velocity, retinal venular caliber, and brain white matter lesions. Kidney outcomes were estimated glomerular filtration rate and albuminuria. RESULTS: In general, we found that kidney disease variants were not associated with vascular phenotypes (127 of 133 tests were nonsignificant). The one exception was rs653178 near SH2B3 (SH2B adaptor protein 3), which showed direction-consistent association with systolic (P = 9.3 ×10(-10)) and diastolic (P = 1.6 ×10(-14)) blood pressure and coronary artery disease (P = 2.2 ×10(-6)), all previously reported. Similarly, the 64 SNPs associated with vascular phenotypes were not associated with kidney phenotypes (187 of 192 tests were nonsignificant), with the exception of 2 high-correlated SNPs at the SH2B3 locus (P = 1.06 ×10(-07) and P = 7.05 ×10(-08)). LIMITATIONS: The combined effect size of the SNPs for kidney and vascular outcomes may be too low to detect shared genetic associations. CONCLUSIONS: Overall, although we confirmed one locus (SH2B3) as associated with both kidney and cardiovascular disease, our primary findings suggest that there is little overlap between kidney and cardiovascular disease risk variants in the overall population. The reciprocal risks of kidney and cardiovascular disease may not be genetically mediated, but rather a function of the disease milieu itself.

Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.

Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.

Urinary sodium excretion and cardiovascular disease mortality.

Comment on: Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerová J, Richart T, Jin Y, Olszanecka A, Malyutina S, Casiglia E, Filipovsk J, Kawecka-Jaszcz K, Nikitin Y, Staessen JA; European Project on Genes in Hypertension (EPOGH) Investigators. Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA. 2011 May 4;305(17):1777-85. PMID: 21540421.

Mortality associated with diabetes and cardiovascular disease in older women.

BACKGROUND: Current guidelines for the prevention of cardiovascular disease (CVD) recommend diabetes as a CVD risk equivalent. However, reports that have examined the risk of diabetes in comparison to pre-existing CVD are lacking among older women. We aimed to assess whether diabetes was associated with a similar risk of total and cause-specific mortality as a history of CVD in older women. METHODOLOGY/PRINCIPAL FINDINGS: We studied 9218 women aged 68 years or older enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a mean follow-up period of 11.7 years and compared all-cause, cardiovascular and coronary heart disease mortality among 4 groups: non-diabetic women with and without existing CVD, diabetic women with and without existing CVD. Mean (SD) age of the participants was 75.2 (5.3) years, 3.5% reported diabetes and 6.8% reported existing CVD. During follow-up, 5117 women died with 36% from CVD. The multivariate adjusted risk of cardiovascular mortality was increased among both non-diabetic women with CVD (hazard ratio (HR) 2.32, 95% CI: 1.97-2.74, P<0.001) and diabetic women without CVD (HR 2.06, CI: 1.62-2.64, P<0.001) compared to non-diabetic women without existing CVD. All-cause, cardiovascular and coronary mortality of non-diabetic women with CVD were not significantly different from diabetic women without CVD. CONCLUSIONS/SIGNIFICANCE: Older diabetic women without CVD have a similar risk of cardiovascular mortality compared to non-diabetic women with pre-existing CVD. The equivalence of diabetes and CVD seems to extend to older women, supporting current guidelines for cardiovascular prevention.

Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type.

Increased peripheral and central nervous system cortisol levels have been reported in Alzheimer's disease (AD) and may reflect dysfunction of cerebral components of the hypothalamic-pituitary-adrenal (HPA) axis. However, brain exposure to high cortisol concentrations may also accelerate disease progression and cognitive decline. The objectives of this study were to investigate whether HPA-axis dysregulation occurs at early clinical stages of AD and whether plasma and CSF cortisol levels are associated with clinical disease progression. Morning plasma and CSF cortisol concentrations were obtained from the subjects with AD dementia, mild cognitive impairment of AD type (MCI-AD), MCI of other type (MCI-O), and controls with normal cognition included in a multicenter study from the German Dementia Competence Network. A clinical and neuropsychological follow-up was performed in a subgroup of participants with MCI-AD, MCI-O, and AD dementia. CSF cortisol concentrations were increased in the subjects with AD dementia or MCI-AD compared with subjects with MCI-O or normal cognition. After controlling for possible confounders including CSF measures of amyloid beta1-42 and total tau, higher baseline CSF cortisol levels were associated with faster clinical worsening and cognitive decline in MCI-AD. The findings suggest that HPA-axis dysregulation occurs at the MCI stage of AD and may accelerate disease progression and cognitive decline.