The combined effect of socioeconomic position and C-reactive protein for predicting incident cardiometabolic disease: Findings from a 14-year follow-up study of the English Longitudinal Study of Ageing (ELSA).

Cardiovascular disease and diabetes are leading causes of morbidity and mortality worldwide. Social inequalities in the distribution of these diseases across the population exist. The aim of the current study was to examine the additive effect of socioeconomic position and a known biological risk marker (C-reactive protein [CRP]) for future incident cardiometabolic disease. We used data from the English Longitudinal Study of Ageing (N = 5410). Tertiles of net financial wealth and CRP (>3 mg/L) were measured at wave 2 (2004/05) and disease incidence (coronary heart disease [CHD], stroke, diabetes/high blood glucose) was reported across the subsequent 14 years of follow-up (2006-2019). Individual diseases were modelled as well as cardiometabolic multimorbidity which was defined as 2 or more incident cardiometabolic disease diagnoses over follow-up. Participants were free from the disease of interest at baseline. Cox proportional hazard and logistic regression analyses were used controlling for sociodemographic, lifestyle and health-related covariates. After adjusting for all covariates, the combination of low wealth and elevated CRP was an independent predictor of incident diabetes/high blood glucose (Hazard Ratio (HR) = 2.14; 95% Confidence Interval (C.I.) = 1.49-3.07), CHD (HR = 2.48, 95% C.I. = 1.63-3.76), stroke (HR = 1.55; 95% C.I. = 1.18-2.04), relative to high wealth/low CRP. Low wealth and elevated CRP was also an independent predictor of incident cardiometabolic multimorbidity (Odds Ratio = 2.22, 95% C.I. = 1.16-4.28) in age and sex adjusted models. The presence of both low wealth and elevated CRP was implicated in the onset of CHD, stroke, diabetes/high blood glucose, and cardiometabolic multimorbidity up to 14 years later, reflecting the role of psychobiological processes in predicting disease burden. Our results reinforce calls for efforts to tackle structural inequalities to improve healthy ageing trajectories.

The effect of beta-adrenergic blockade on inflammatory and cardiovascular responses to acute mental stress.

Acute mental stress elicits increases in plasma cytokine concentrations in humans, but the underlying mechanisms remain poorly understood. We assessed the impact of beta-adrenergic blockade on plasma interleukin 6 (IL-6) and IL-1 receptor antagonist (IL-1Ra) responses in a parallel group, double-blind randomised placebo-controlled trial involving 64 healthy young adult volunteers. Participants were administered 80 mg slow-release propranolol or placebo daily for 7 days before the stress testing session in which responses to 3 behavioural challenges (public speaking, mirror tracing, mental arithmetic) were evaluated. Propranolol administration was associated with reduced baseline levels of heart rate and IL-1Ra, and systolic blood pressure (BP) in men. Tasks stimulated increased plasma IL-6 concentrations sampled 45 min and 75 min after challenge, but these responses were blocked by propranolol in men (p < 0.001). Propranolol did not influence IL-6 responses in women, or IL-1Ra in either sex. Blood pressure and heart rate increased markedly during the tasks, but there was no differential stress reactivity in propranolol and placebo conditions. The results of the study support a role of sympathetic nervous system activation in stimulating acute IL-6 responses to stress, but only in men. The reasons for the differences between men and women remain to be resolved.

Hybrid Bone SPECT/CT Imaging in Evaluation of Chronic Low Back Pain: Correlation with Facet Joint Arthropathy.

BACKGROUND: Evidence to support the use of bone hydroxydiphosphonate (HDP) single photon emission computed tomography (SPECT/CT) in patients with facetogenic low back pain (LBP) is still limited. In this study we compared the scintigraphic patterns on bone SPECT/CT with the degree of structural facet joint (FJ) degeneration on CT in patients with LBP. METHODS: Ninety-nine consecutive patients with LBP were prospectively evaluated. Patients with known or suspected malignancy, trauma, infectious processes, chronic inflammatory diseases, and previous surgery were excluded. The effect of LBP on the daily quality of life was assessed with the Oswestry disability index (ODI). The Pathria grading system was used to score FJ degeneration on CT scans. The correlation between the degree of FJ degeneration and osteoblastic activity on SPECT/CT was analyzed with Kappa statistics. RESULTS: Ninety-nine patients were included (59 female, mean age 56.2 years). The mean ODI score was 38.5% (range, 8% to 72%). In all, 792 FJ (L2-3 to L5-S1) were examined. Of the FJs, 49.6% were Pathria grade 0-1 (normal to mild degeneration) on CT, 35% were grade 2 (moderate degeneration), and 16% were grade 3 (severe degeneration). Sixty-seven percent of the patients had scintigraphically active FJs on SPECT/CT. Sixty-nine percent of Pathria grade 3 FJs were scintigraphically active; 5.5% and 16.8% of Pathria grade 0-1 and Pathria grade 2, respectively, were active. Of the metabolically active FJs, 71.4% were at the L4-5/L5-S1 levels. CONCLUSIONS: The ability of SPECT/CT to precisely localize scintigraphically active FJs may provide significant improvement in the diagnosis and treatment of patients with LBP. In this study we demonstrate that in >40% of FJs, the scintigraphic patterns on SPECT/CT did not correlate with the degree of degeneration on CT.

Hybrid Bone Single Photon Emission Computed Tomography Imaging in Evaluation of Chronic Low Back Pain: Correlation with Modic Changes and Degenerative Disc Disease.

BACKGROUND AND OBJECTIVE: Multiple radiologic modalities are used in the evaluation of patients with low back pain (LBP). Only limited evidence currently exists to support the use of bone hydroxydiphosphonate single photon emission computed tomography (SPECT/CT) in patients with Modic changes (MCs) and degenerative disc disease. The aim of this study was to assess the value of the hybrid bone SPECT/CT imaging in patients with chronic LBP. We evaluate the correlation of hybrid bone SPECT/CT imaging patterns with MCs and disc abnormalities on magnetic resonance imaging (MRI). METHODS: This was a prospective study. Ninety-nine consecutive patients with LBP from a single center. The degree of lumbar intervertebral disc and endplate degeneration on MRI and osteoblastic activity was shown on SPECT/CT. These 99 consecutive patients with LBP were prospectively evaluated. Patients with contemporary lumbosacral spine MRI and bone SPECT/CT were included. Patients with known or suspected malignancy, trauma, infectious processes, and previous surgery were excluded. The effect of LBP on the daily quality of life was assessed using Oswestry disability index. We analyzed the correlation between the degenerative changes at the intervertebral disc spaces and endplates on MRI and bone SPECT/CT findings using receiver operating characteristic curve analysis and Kappa statistics. The Pfirrmann grading system was used to score the severity of disc space degeneration on MRI scans. RESULTS: A total of 99 patients were included in the study (58 women, 41 men; mean age, 56.2 years). Mean Oswestry disability index score was 38.5% (range, 8%-72%). The L2-3 through to L5-S1 levels were studied. MCs were found in 54% of patients. Of the 396 levels examined 85 were found to have MCs (21.5%). The most affected levels were L4-5 (31.3%) and L5-S1 (40.9%). Pfirrmann grade 5 disc space (72.9%) was associated with MC (Pp<0.001). MC (70.6%) and Pfirrmann grade 5 disc spaces (73%) resulted in scintigraphically active endplate/disc space on SPECT/CT (P< 0.001). Bone SPECT/CT showed high metabolic activity in 96.1% of endplates with MC type I, 56% with MC type II, and 77.8% with MC type III. CONCLUSIONS: In this study we found a high agreement between MCs and increased metabolic activity on bone SPECT/CT imaging. MC type 1 and Pfirrmann grade 5 were the best binary predictors for positivity on bone SPECT/CT and had equivalent correlations. Lower vertebral levels in the lumbar spine were associated with higher degree of disc degeneration, high frequency of MCs, and positivity on bone SPECT/CT.

Assessing the translational feasibility of pharmacological drug memory reconsolidation blockade with memantine in quitting smokers.

RATIONALE: Preclinical reconsolidation research offers the first realistic opportunity to pharmacologically weaken the maladaptive memory structures that support relapse in drug addicts. N-methyl D-aspartate receptor (NMDAR) antagonism is a highly effective means of blocking drug memory reconsolidation. However, no research using this approach exists in human addicts. OBJECTIVES: The objective of this study was to assess the potential and clinical outcomes of blocking the reconsolidation of cue-smoking memories with memantine in quitting smokers. METHODS: Fifty-nine dependent and motivated to quit smokers were randomised to one of three groups receiving the following: (1) memantine with or (2) without reactivation of associative cue-smoking memories or (3) reactivation with placebo on their target quit day in a double-blind manner. Participants aimed to abstain from smoking for as long as possible. Levels of smoking and FTND score were assessed prior to intervention and up to a year later. Primary outcome was latency to relapse. Subjective craving measures and attentional bias to smoking cues were assessed in-lab. RESULTS: All study groups successfully reduced their smoking up to 3 months. Memantine in combination with smoking memory reactivation did not affect any measure of smoking outcome, reactivity or attention capture to smoking cues. CONCLUSIONS: Brief exposure to smoking cues with memantine did not appear to weaken these memory traces. These findings could be due to insufficient reconsolidation blockade by memantine or failure of exposure to smoking stimuli to destabilise smoking memories. Research assessing the treatment potential of reconsolidation blockade in human addicts should focus on identification of tolerable drugs that reliably block reward memory reconsolidation and retrieval procedures that reliably destabilise strongly trained memories.

Hostility and physiological responses to acute stress in people with type 2 diabetes.

OBJECTIVE: Hostility is associated with cardiovascular mortality and morbidity, and one of the mechanisms may involve heightened reactivity to mental stress. However, little research has been conducted in populations at high risk for cardiovascular disease. The aim of the present study was to assess the relationship between hostility and acute stress responsivity in individuals with Type 2 diabetes. METHODS: A total of 140 individuals (median age [standard deviation] 63.71 [7.00] years) with Type 2 diabetes took part in laboratory-based experimental stress testing. Systolic blood pressure, diastolic blood pressure, heart rate, plasma interleukin-6 (IL-6), and salivary cortisol were assessed at baseline, during two stress tasks, and 45 and 75 minutes later. Cynical hostility was assessed using the Cook Medley Cynical Hostility Scale. RESULTS: Participants with greater hostility scores had heightened increases in IL-6 induced by the acute stress tasks (B = 0.082, p = .002), independent of age, sex, body mass index, smoking, household income, time of testing, medication, and baseline IL-6. Hostility was inversely associated with cortisol output poststress (B = -0.017, p = .002), independent of covariates. No associations between hostility and blood pressure or heart rate responses were observed. CONCLUSIONS: Hostile individuals with Type 2 diabetes may be susceptible to stress-induced increases in inflammation. Further research is needed to understand if such changes increase the risk of cardiovascular disease in this population.

Blunted glucocorticoid and mineralocorticoid sensitivity to stress in people with diabetes.

Psychological stress may contribute to type 2 diabetes but mechanisms are still poorly understood. In this study, we examined whether stress responsiveness is associated with glucocorticoid and mineralocorticoid sensitivity in a controlled experimental comparison of people with type 2 diabetes and non-diabetic participants. Thirty-seven diabetes patients and 37 healthy controls underwent psychophysiological stress testing. Glucocorticoid (GR) and mineralocorticoid sensitivity (MR) sensitivity were measured by dexamethasone- and prednisolone-inhibition of lipopolysaccharide (LPS)-induced interleukin (IL) 6 levels, respectively. Blood pressure (BP) and heart rate were monitored continuously, and we periodically assessed salivary cortisol, plasma IL-6 and monocyte chemotactic protein (MCP-1). Following stress, both glucocorticoid and mineralocorticoid sensitivity decreased among healthy controls, but did not change in people with diabetes. There was a main effect of group on dexamethasone (F(1,74)=6.852, p=0.013) and prednisolone (F(1,74)=7.295, p=0.010) sensitivity following stress at 45 min after tasks. People with diabetes showed blunted stress responsivity in systolic BP, diastolic BP, heart rate, IL-6, MCP-1, and impaired post-stress recovery in heart rate. People with Diabetes had higher cortisol levels as measured by the total amount excreted over the day and increased glucocorticoid sensitivity at baseline. Our study suggests that impaired stress responsivity in type-2 diabetes is in part due to a lack of stress-induced changes in mineralocorticoid and glucocorticoid sensitivity.

Objectively assessed physical activity, adiposity, and inflammatory markers in people with type 2 diabetes.

OBJECTIVE: Inflammatory processes may play an important role in the development of acute coronary syndromes in people with type 2 diabetes; thus, strategies to control inflammation are of clinical importance. We examined the cross-sectional association between objectively assessed physical activity and inflammatory markers in a sample of people with type 2 diabetes. METHODS: Participants were 71 men and 41 women (mean age=63.9±7 years), without a history of cardiovascular disease, drawn from primary care clinics. Physical activity was objectively measured using waist-worn accelerometers (Actigraph GT3X) during waking hours for seven consecutive days. RESULTS: We observed inverse associations between moderate-to-vigorous physical activity (per 10 min) with plasma interleukin-6 (B=-0.035, 95% CI -0.056 to -0.015), interleukin-1ra (B=-0.033, 95% CI -0.051 to -0.015), and monocyte chemotactic protein-1 (B=-0.011, 95% CI -0.021 to 0.000). These associations largely persisted in multivariable adjusted models, although body mass index considerably attenuated the effect estimate. CONCLUSIONS: These data demonstrate an inverse association between physical activity and inflammatory markers in people with type 2 diabetes.

Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load.

Psychological stress-related processes are thought to contribute to the development and progression of type 2 diabetes, but the biological mechanisms involved are poorly understood. Here, we tested the notion that people with type 2 diabetes experience chronic allostatic load, manifest as dynamic disturbances in reactivity to and recovery from stress across multiple (cardiovascular, neuroendocrine, inflammatory, metabolic) biological systems, coupled with heightened experience of chronic life stress. We carried out an experimental comparison of 140 men and women aged 50-75 y with type 2 diabetes and 280 nondiabetic individuals matched on age, sex, and income. We monitored blood pressure (BP) and heart rate, salivary cortisol, plasma interleukin (IL)-6, and total cholesterol in response to standardized mental stress, and assessed salivary cortisol over the day. People with type 2 diabetes showed impaired poststress recovery in systolic and diastolic BP, heart rate and cholesterol, and blunted stress reactivity in systolic BP, cortisol, cholesterol, and IL-6. Cortisol and IL-6 concentrations were elevated, and cortisol measured over the day was higher in the type 2 diabetes group. Diabetic persons reported greater depressive and hostile symptoms and greater stress experience than did healthy controls. Type 2 diabetes is characterized by disruption of stress-related processes across multiple biological systems and increased exposure to life stress. Chronic allostatic load provides a unifying perspective with implications for etiology and patient management.

The association between cortisol response to mental stress and high-sensitivity cardiac troponin T plasma concentration in healthy adults.

OBJECTIVES: The objective of this study was to examine the association between cortisol response to mental stress and high-sensitivity cardiac troponin T (hs-cTnT) in healthy older individuals without history of cardiovascular disease (CVD). BACKGROUND: Mental stress is a recognized risk factor for CVD, although the mechanisms remain unclear. Cortisol, a key stress hormone, is associated with coronary atherosclerosis and may accentuate structural and functional cardiac disease. METHODS: This cross-sectional study involved 508 disease-free men and women aged 53 to 76 years drawn from the Whitehall II epidemiological cohort. We evaluated salivary cortisol response to standardized mental stress tests (exposure) and hs-cTnT plasma concentration using a high-sensitivity assay (outcome). We measured coronary calcification using electron-beam dual-source computed tomography and Agatston scores. RESULTS: After adjustment for demographic and clinical variables associated with CVD as well as for inflammatory factors, we found a robust association between cortisol response and detectable hs-cTnT (odds ratio [OR]: 3.98; 95% confidence interval [CI]: 1.60 to 9.92; p = 0.003). The association remained when we restricted the analysis to participants without coronary calcification (n = 222; OR: 4.77; 95% CI: 1.22 to 18.72; p = 0.025) or when we further adjusted for coronary calcification in participants with positive Agatston scores (n = 286; OR: 7.39; 95% CI: 2.22 to 26.24; p = 0.001). CONCLUSIONS: We found that heightened cortisol response to mental stress was associated with detectable plasma levels of cTnT using high-sensitivity assays in healthy participants, independently of coronary atherosclerosis. Further research is needed to understand the role of psychosocial stress in the pathophysiology of cardiac cell damage.

Systematic review of epidemiological studies on health effects associated with management of solid waste.

BACKGROUND: Management of solid waste (mainly landfills and incineration) releases a number of toxic substances, most in small quantities and at extremely low levels. Because of the wide range of pollutants, the different pathways of exposure, long-term low-level exposure, and the potential for synergism among the pollutants, concerns remain about potential health effects but there are many uncertainties involved in the assessment. Our aim was to systematically review the available epidemiological literature on the health effects in the vicinity of landfills and incinerators and among workers at waste processing plants to derive usable excess risk estimates for health impact assessment. METHODS: We examined the published, peer-reviewed literature addressing health effects of waste management between 1983 and 2008. For each paper, we examined the study design and assessed potential biases in the effect estimates. We evaluated the overall evidence and graded the associated uncertainties. RESULTS: In most cases the overall evidence was inadequate to establish a relationship between a specific waste process and health effects; the evidence from occupational studies was not sufficient to make an overall assessment. For community studies, at least for some processes, there was limited evidence of a causal relationship and a few studies were selected for a quantitative evaluation. In particular, for populations living within two kilometres of landfills there was limited evidence of congenital anomalies and low birth weight with excess risk of 2 percent and 6 percent, respectively. The excess risk tended to be higher when sites dealing with toxic wastes were considered. For populations living within three kilometres of old incinerators, there was limited evidence of an increased risk of cancer, with an estimated excess risk of 3.5 percent. The confidence in the evaluation and in the estimated excess risk tended to be higher for specific cancer forms such as non-Hodgkin's lymphoma and soft tissue sarcoma than for other cancers. CONCLUSIONS: The studies we have reviewed suffer from many limitations due to poor exposure assessment, ecological level of analysis, and lack of information on relevant confounders. With a moderate level confidence, however, we have derived some effect estimates that could be used for health impact assessment of old landfill and incineration plants. The uncertainties surrounding these numbers should be considered carefully when health effects are estimated. It is clear that future research into the health risks of waste management needs to overcome current limitations.