Long-term interleukin-6 levels and subsequent risk of coronary heart disease: Two new prospective studies and a systematic review

Background The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Methods and Findings Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual'') IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels). Conclusions Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CH

Association between the metabolic syndrome and its components and gait speed among U.S. adults aged 50 years and older: a cross-sectional analysis

BACKGROUND: To examine the relationship between the metabolic syndrome and its components and gait speed among older U.S. men and women. Whether these associations are independent of physical activity was also explored. METHODS: Eight hundred and thirty-five men and 850 women aged ≥50 years from the continuous National Health and Nutrition Examination Survey 1999–2002 were examined. We used the definition of the metabolic syndrome developed by the U.S. National Cholesterol Education Program Adult Treatment Panel III. Gait speed was measured with a 6.10-meter timed walk examination. RESULTS: The prevalence of the metabolic syndrome was 40.2% in men and 45.6% in women (P = .127). The prevalence of gait speed impairment was 29.3% in men and 12.5% in women (P < .001). No association was found between the metabolic syndrome and gait speed impairment. After including the individual components of the metabolic syndrome in a logistic model adjusted for age and leisure-time physical activity, abdominal obesity, low HDL cholesterol, and high fasting glucose were significantly associated with gait speed impairment among women (adjusted odds ratio [AOR] = 0.48, 95% confidence interval [CI] = 0.26 to 0.89; AOR = 2.26, 95% CI = 1.08 to 4.75; and AOR = 2.05, 95% CI = 1.12 to 3.74, respectively). Further adjustment for race/ethnicity, education, smoking status, alcohol consumption, arthritis status, and use of an assistive device attenuated these associations; among women, abdominal obesity and low HDL cholesterol remained significantly associated with gait speed impairment (AOR = 0.37, 95% CI = 0.18 to 0.76 and AOR = 2.45, 95% CI = 1.07 to 5.63, respectively) while the association between hyperglycemia and impaired gait speed attenuated to nonsignificance. CONCLUSION: Among women, gait speed impairment is associated with low HDL cholesterol and inversely with abdominal obesity. These associations may be sex-dependent and warrant further research

The influence of multimorbidity on clinical progression of dementia in a population-based cohort.

Co-occurrence with other chronic diseases may influence the progression of dementia, especially in case of multiple chronic diseases. We aimed to verify whether multimorbidity influenced cognitive and daily functioning during nine years after dementia diagnosis compared with the influence in persons without dementia.In the Kungsholmen Project, a population-based cohort study, we followed 310 persons with incident dementia longitudinally. We compared their trajectories with those of 679 persons without dementia. Progression was studied for cognition and activities of daily life (ADLs), measured by MMSE and Katz Index respectively. The effect of multimorbidity and its interaction with dementia status was studied using individual growth models.The mean (SD) follow-up time was 4.7 (2.3) years. As expected, dementia related to both the decline in cognitive and daily functioning. Irrespective of dementia status, persons with more diseases had significantly worse baseline daily functioning. In dementia patients having more diseases also related to a significantly faster decline in daily functioning. Due to the combination of lower functioning in ADLs at baseline and faster decline, dementia patients with multimorbidity were about one to two years ahead of the decline of dementia patients without any co-morbidity. In persons without dementia, no significant decline in ADLs over time was present, nor was multimorbidity related to the decline rate. Cognitive decline measured with MMSE remained unrelated to the number of diseases present at baseline.Multimorbidity was related to baseline daily function in both persons with and without dementia, and with accelerated decline in people with dementia but not in non-demented individuals. No relationship of multimorbidity with cognitive functioning was established. These findings imply a strong interconnection between physical and mental health, where the greatest disablement occurs when both somatic and mental disorders are present

Comprehensive Geriatric Assessment

The CGA is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults in order to develop a coordinated plan to maximize overall health with aging. At present, no standard criteria are available to readily identify patients who are likely to benefit from the CGA. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. Evidence coming from RCTs and large systematic reviews and meta-analyses suggests that the healthcare setting may influence the effectiveness of CGA programs. Home CGA programs as well as the CGA performed in hospital have been shown to be consistently beneficial for several health outcomes. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cognitive impairment and dementia. The CGA, capable to effectively exploring multiple domains in older age, is indeed the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathological risk and the residual skills, as well as the shortand long-term prognosis, i.e., the Multidimensional Prognostic Index (MPI), to facilitate the clinical decision making on the personalized care plan of older subjects