The SMART study was a trial of intermittent use of antiretroviral therapy (ART) (drug conservation DC) versus continuous use of ART (viral suppression VS) as a strategy to reduce toxicities, ...including cardiovascular disease (CVD) risk. We studied the predictive value of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and mortality in HIV-infected patients who were enrolled in SMART beyond other measured CVD risk factors.
A blood sample was available in 5098 participants who were enrolled in the SMART study for the measurement of IL-6, hsCRP and D-dimer. Hazard ratios (HR) with 95% CI for CVD events were estimated for each quartile (Q) for each biomarker vs the 1(st) quartile and for 1 SD higher levels. For both treatment groups combined, unadjusted and adjusted HRs were determined using Cox regression models.
There were 252 participants who had a CVD event over a median follow-up of 29 months. Adjusted HRs (95% CI) for CVD for Q4 vs Q1 were 4.65 (2.61, 8.29), 2.10 (1.40, 3.16), and 2.14 (1.38, 3.33) for IL-6, hsCRP and D-dimer, respectively. Associations were similar for the DC and VS treatment groups (interaction p-values were >0.30). The addition of the three biomarkers to a model that included baseline covariates significantly improved model fit (p<0.001). Area under the curve (AUC) estimates improved with inclusion of the three biomarkers in a model that included baseline covariates corresponding to other CVD risk factors and HIV factors (0.741 to 0.771; p<0.001 for difference).
In HIV-infected individuals, IL-6, hsCRP and D-dimer are associated with an increased risk of CVD independent of other CVD risk factors. Further research is needed to determine whether these biomarkers can be used to improve CVD risk prediction among HIV positive individuals.
The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's ...disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts.
This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age ≥53 years), the Kungsholmen Project (KP) (n = 905, age ≥75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age ≥65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index.
For the ANU-ADRI using available data, the MAP study c-statistic was 0·637 (95% CI 0·596-0·678), for the KP study it was 0·740 (0·712-0·768) and for the CVHS it was 0·733 (0·691-0·776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625).
A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up.
Background.The association between hepatitis C virus (HCV) infection and coronary artery disease (CAD) is controversial. We conducted this study to determine and quantify this association. Methods.We ...used an established, national, observational cohort of all HCV-infected veterans receiving care at all Veterans Affairs facilities, the Electronically Retrieved Cohort of HCV Infected Veterans, to identify HCV-infected subjects and HCV-uninfected control subjects. We used the Cox proportional-hazards model to determine the risk of CAD among HCV-infected subjects and control subjects. Results.We identified 82,083 HCV-infected and 89,582 HCV-uninfected subjects. HCV-infected subjects were less likely to have hypertension, hyperlipidemia, and diabetes but were more likely to abuse alcohol and drugs and to have renal failure and anemia. HCV-infected subjects had lower mean (± standard deviation) total plasma cholesterol (175 ± 40.8 mg/dL vs. 198 ± 41.0 mg/dL), low-density lipoprotein cholesterol (102 ± 36.8 mg/dL vs. 119 ± 38.2 mg/dL), and triglyceride (144 ± 119 mg/dL vs. 179 ± 151 mg/dL) levels, compared with HCV-uninfected subjects (P<.001 for all comparisons). In multivariable analysis, HCV infection was associated with a higher risk of CAD (hazard ratio, 1.25; 95% confidence interval, 1.20-1.30). Traditional risk factors (age, hypertension, chronic obstructive pulmonary disease, diabetes, and hyperlipidemia) were associated with a higher risk of CAD in both groups, whereas minority race and female sex were associated with a lower risk of CAD. Conclusions.HCV-infected persons are younger and have lower lipid levels and a lower prevalence of hypertension. Despite a favorable risk profile, HCV infection is associated with a higher risk of CAD after adjustment for traditional risk factors.
The study of the incidence and prevalence of dementia is important to understand the distribution of dementing illness among age and sex groups, and for the detection of possible causes of these ...disorders. A variation in the incidence or prevalence of dementia, especially Alzheimer's disease (AD) by region or specific populations can be because of greater or lesser exposure to the causal agents of dementia. For example, in the past the striking differences in the incidence of coronary heart disease (CHD) led to the understanding of the relationship between dietary factors, such as saturated fat and dietary cholesterol, and the incidence of CHD. However, there is a high prevalence of dementia in elderly individuals around the world, and multiple studies conducted in industrialized and nonindustrialized countries have shown an age-standardized prevalence of dementia ranging from 5% to 7% in most countries. Dementia is not a specific disease but rather a constellation of cognitive changes and disability due to several "causes," i.e., AD, Lewy bodies, vascular disease, drugs, and alcohol. Whether there is a trend for reduced incidence of dementia has to be further evaluated. It is possible that the improvement in the treatments of risk factors, especially vascular disease, has resulted in decreased incidence. However, this could result in an increase in prevalence, since the improved therapies for risk factors will lead to increased longevity in patients with dementia.
The increasing longevity of the population has resulted in dementia becoming a leading cause of both death and disability. Dementia is not a single disease. Studies of rare Mendelian disorders have ...documented that Alzheimer's disease, the most common cause of dementia, is associated with a long incubation period from amyloid deposition to neurodegeneration to mild cognitive impairment and dementia. There are three broad hypotheses related to the causes of Alzheimer's dementia: (1) an aging process; (2) brain vascular disease; and (3) metabolic abnormalities associated with either increased production of amyloid-β or decreased clearance from the brain. Therefore, research on the early stages of the dementia process are of high priority. This paper reports that higher energy intake in both the Nurses’ Health Study and Health Professionals Follow-up Study is associated with very early symptoms that lead to mild cognitive impairment and dementia. The results are very interesting but hard to interpret because they also show that higher energy intake is not related to body mass index, a very unusual observation. A likely hypothesis is that there is an association between reporting of dietary intake and subjective symptoms, i.e. reporting bias, accounting for their results.
In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug ...conservation DC) than continuous ART (viral suppression VS).We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis.
Stored samples were used to measure six biomarkers: high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), amyloid A, amyloid P, D-dimer, and prothrombin fragment 1+2. Two studies were conducted: (1) a nested case-control study for studying biomarker associations with mortality, and (2) a study to compare DC and VS participants for biomarker changes. For (1), markers were determined at study entry and before death (latest level) for 85 deaths and for two controls (n = 170) matched on country, age, sex, and date of randomization. Odds ratios (ORs) were estimated with logistic regression. For each biomarker, each of the three upper quartiles was compared to the lowest quartile. For (2), the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following randomization. Higher levels of hsCRP, IL-6, and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality. Unadjusted ORs (highest versus lowest quartile) were 2.0 (95% confidence interval CI, 1.0-4.1; p = 0.05), 8.3 (95% CI, 3.3-20.8; p < 0.0001), and 12.4 (95% CI, 4.2-37.0; p < 0.0001), respectively. Associations were significant after adjustment, when the DC and VS groups were analyzed separately, and when latest levels were assessed. IL-6 and D-dimer increased at 1 mo by 30% and 16% in the DC group and by 0% and 5% in the VS group (p < 0.0001 for treatment difference for both biomarkers); increases in the DC group were related to HIV-RNA levels at 1 mo (p < 0.0001). In an expanded case-control analysis (four controls per case), the OR (DC/VS) for mortality was reduced from 1.8 (95% CI, 1.1-3.1; p = 0.02) to 1.5 (95% CI, 0.8-2.8) and 1.4 (95% CI, 0.8-2.5) after adjustment for latest levels of IL-6 and D-dimer, respectively.
IL-6 and D-dimer were strongly related to all-cause mortality. Interrupting ART may further increase the risk of death by raising IL-6 and D-dimer levels. Therapies that reduce the inflammatory response to HIV and decrease IL-6 and D-dimer levels may warrant investigation.
To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.
One thousand six hundred fifty-eight elderly ambulatory ...adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria.
During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval CI) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23-4.13) and 1.53 (95% CI: 1.06-2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02-4.83) and 1.69 (95% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.
Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.
Abstract
Epidemiology is the study of epidemics. It is a biological science that includes expertise in many disciplines in social and behavioral sciences. Epidemiology is also a key component of ...preventive medicine and public health. Unfortunately, over recent years, academic epidemiology has lost its relationship with preventive medicine, as well as much of its focus on epidemics. The new “-omics” technologies to measure risk factors and phenotypes, and advances in genomics (e.g., host susceptibility) consistent with good epidemiology methods will likely enhance epidemiology research. There is a need based on these new technologies to modify training, especially for the first-level doctorate epidemiologist.
Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these ...inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline.
We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9.
We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk.
We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline.
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•Higher baseline blood C-reactive protein levels were correlated with thinner posterior cingulate cortex, at study year 9.•Higher metabolic risk was strongly associated with higher blood CRP levels.•Higher blood CRP levels mediated an effect between higher metabolic risk and thinner cortex.•A polygenic score of AD risk variants in immune-related genes was associated with thinner cortex but not with CRP levels.
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