Mental stress, socioeconomic status and cardiovascular disease: integrating socioeconomic circumstances into the paradigm of psycho-neuro-endocrino-immunology

Background Mental stress is a recognized risk factor and trigger for heart disease. Socioeconomic status (SES) is associated with morbidity and mortality, with low SES people having poorer health compared to their counterparts. I hypothesised that those two factors may interact with each other, so that when they are present simultaneously the total harmful effect is more than the sum of the two risk factors alone. Research aim My aim was to test whether lower SES interacts with mental stress and amplifies its effect on heart disease, so that the effect of mental stress on heart disease would be more pronounced in people from low SES backgrounds. Studies I carried out three studies. For my first study, I analysed data from a cross-sectional study involving about 500 disease-free middle/old-aged men and women drawn from the Whitehall II epidemiological cohort. I evaluated their salivary cortisol responses to standardized mental stress tests (exposure variable) and their cardiac troponin T plasma concentration (a marker of heart damage) using a high-sensitivity assay (HS-CTnT, outcome variable). I also used measures of coronary calcification levels using electron-beam dual-source computed tomography and Agatston scores. After adjustment for demographic and clinical variables associated with heart disease as well as for inflammatory factors, I found a robust association between cortisol response to mental stress and detectable troponin T (odds ratio [OR] =3.8, 95% confidence interval [CI] =1.5-9.4, P =0.005). The association remained when I restricted the analysis to participants without coronary calcification (n =222, OR =4.8; 95% CI =1.2-18.3; P =0.023) or when I further adjusted for coronary calcification in participants with positive Agatston scores (n =286, OR =6.2, 95% CI =1.9-20.6; P =0.003). In analyses stratified by SES, there was a trend showing that the lower the SES was, the higher the OR, although this trend was not significant (P >0.05). In my second study, I selected about 67,000 male and female participants from the Health Survey for England who were 35 years or older, free of cancer and cardiovascular disease at baseline, and living in private households in England from 1994 to 2004. Selection used stratified random sampling (hence representative of the nation), and participants were linked prospectively to mortality records from the Office of National Statistics (mean follow-up, 8.2 years). Mental stress was measured using the 12-item General Health Questionnaire, and SES was indexed by occupational class. The crude incidence rates for heart disease and all-cause mortality of the cohort were 1.9 (95%CI =1.7-2.0) and 14.5 (95%CI =14.2-14.8) per 1,000 person-years. After adjustment for age and sex, mental stress was associated with increased mortality rates. In a stratified analysis, the association of mental stress with the outcomes differed with SES, with the strongest associations being observed in the lowest SES categories (the adjusted P values for interaction were 0.012 for all-cause mortality and 0.047 for heart disease mortality). My third study involved about 80,000 post-menopausal women selected from the United Kingdom Collaborative Trial of Ovarian Cancer Screening study, who were followed up for about three years on average. Mental stress was measured using the hopelessness/helplessness index and incident heart disease was assessed using hospital electronic records. The overall incidence rate of hospitalisation for acute heart disease event was 2.7 per 1,000 person years (95% CI=2.5-3.0). The augmented incidence for people who experienced mental stress was higher in people of low SES, medium in people of medium SES, and lower in people of high SES (adjusted P value for interaction =0.013). Conclusion These studies suggest that the interaction between socioeconomic status and mental stress is associated with ischemic heart disease, in such a way that people in low socioeconomic circumstances are more vulnerable to the negative effects of mental stress. In other words, the harmful effect of mental stress for human cardiac health may be modified by socioeconomic position and rendered more deleterious for people from disadvantaged backgrounds. Further research is needed to disentangle the dynamics of this effect amplification

Low socioeconomic status and psychological distress as synergistic predictors of mortality from stroke and coronary heart disease.

The purpose of this study was to test whether lower socioeconomic status (SES) augments the effect of psychological distress on mortality from stroke or coronary heart disease (CHD)

Individualised headband simulation test for predicting outcome after percutaneous bone conductive implantation.

Trans-cutaneous bone conduction (BC) stimulators, when coupled to the HB (BC-HB), are generally used to predict the results that could be achieved after bone conductive implant (BCI) surgery, and their performance is generally considered inferior to that provided by the definitive percutaneous system. The aim of the present study was to compare the performances between BC-HB and BCI of the same typology, when the former's sound processor is fitted in accordance to the individual auditory situation. Twenty-two patients selected for surgical application of a BCI were evaluated and the same audiological protocol was used to select the candidate and assess the final outcome. The BC-HB was properly fitted based on individual hearing loss and personal auditory targets, and tested as primary step of the protocol to obtain the most reliable predictive value. The BAHA Divino and BP100 sound processors were applied in 12 patients with conductive/mixed hearing loss (CMHL) and in 10 subjects with single sided deafness (SSD). Audiometric evaluation included the pure tone average (PTA3) threshold between 250-1000 Hz; the PTA thresholds at 2000 and 4000 Hz; intelligibility scores as percentage of word recognition (WRS) in quiet and in noise; and subjective evaluation of perceived sound quality by a visual analogue scale (VAS). Statistical evaluation with a student's t test was used for assessment of efficacy of BC-HB and BCI compared with the unaided condition. Spearman's Rho coefficient was used to confirm the reliability of the BC-HB simulation test as a predictor of definitive outcome. The results showed that the mean PTA difference between BCI and BC-HB ranged from 2.54 to 8.27 decibels in the CMHL group and from 1.27 to 3.9 decibels in the SSD group. Compared with the BC-HB, BCI showed a better WRS both in CMHL (16% in quiet and 12% in noise) and in SSD (5% in quiet and a 1% in noise) groups. Spearman's Rho coefficient, calculated for PTA, WRS in quiet and in noise and VAS in the two aided conditions, showed a significant correlation between BC-HB and BCI, between PTA and VAS and between WRS in quiet and VAS. It is possible to conclude that the headband test, when the sound processor of the selected bone conductive implant is fitted and personalised for individual hearing loss and auditory targets of the candidate, may provide highly predictive data of the definitive outcome after BCI implant surgery

Temporal patterns in the recorded annual incidence of common mental disorders over two decades in the United Kingdom: a primary care cohort study

BACKGROUND: Common mental disorders (CMDs) including depression, anxiety, and stress are very common, but it is unclear whether the last decades of social, economic, and political change have impacted incidence of CMD. This study explored temporal trends in the recorded incidence of CMD in the United Kingdom. METHODS: We used data from general practices in the United Kingdom (Clinical Practice Research Datalink) to estimate the annual recorded incidence of CMD for 2000-2020, including symptoms, diagnosis, or pharmaceutical treatment. Trends were explored by sex, age, ethnicity, region, deprivation, and comorbidity. RESULTS: We included 29 480 164 individuals who were followed up for 12.5 years on average (s.d. = 6.4 years). The recorded incidence of CMD episodes was 55.9 per 1000 person-years in 2000 [95% confidence interval (CI) 55.8-56.1], increasing to 79.6 per 1000 person-years in 2019 (95% CI 79.5-79.8). Females had higher recorded incidence rates, as did those living in more deprived areas. We observed striking patterns by age over time, with rates in ages 16-24 increasing from 40.2 per 1000 in 2000 (95% CI 39.8-40.5), to 107.8 per 1000 in 2019 (95% CI 107.0-108.6). In contrast, the rates in those aged ≥55 years decreased since 2014. There were differing patterns of incidence by ethnic group, with a steeper increase in Asian, Black, and mixed groups in recent years. CONCLUSIONS: Overall, the incidence of recorded CMD in the UK general practice increased between 2000 and 2019 with a small decrease in 2020. The overall trends obscured important differences across population subgroups, which may have implications for prevention

Temporal patterns in the recorded annual incidence of common mental disorders over two decades in the United Kingdom: a primary care cohort study

BACKGROUND: Common mental disorders (CMDs) including depression, anxiety, and stress are very common, but it is unclear whether the last decades of social, economic, and political change have impacted incidence of CMD. This study explored temporal trends in the recorded incidence of CMD in the United Kingdom. METHODS: We used data from general practices in the United Kingdom (Clinical Practice Research Datalink) to estimate the annual recorded incidence of CMD for 2000-2020, including symptoms, diagnosis, or pharmaceutical treatment. Trends were explored by sex, age, ethnicity, region, deprivation, and comorbidity. RESULTS: We included 29 480 164 individuals who were followed up for 12.5 years on average (s.d. = 6.4 years). The recorded incidence of CMD episodes was 55.9 per 1000 person-years in 2000 [95% confidence interval (CI) 55.8-56.1], increasing to 79.6 per 1000 person-years in 2019 (95% CI 79.5-79.8). Females had higher recorded incidence rates, as did those living in more deprived areas. We observed striking patterns by age over time, with rates in ages 16-24 increasing from 40.2 per 1000 in 2000 (95% CI 39.8-40.5), to 107.8 per 1000 in 2019 (95% CI 107.0-108.6). In contrast, the rates in those aged ≥55 years decreased since 2014. There were differing patterns of incidence by ethnic group, with a steeper increase in Asian, Black, and mixed groups in recent years. CONCLUSIONS: Overall, the incidence of recorded CMD in the UK general practice increased between 2000 and 2019 with a small decrease in 2020. The overall trends obscured important differences across population subgroups, which may have implications for prevention

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

The effects of six-day SSRI administration on diurnal cortisol secretion in healthy volunteers

RATIONALE: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been widely reported in depression, and evidence suggests that selective serotonin reuptake inhibitors (SSRIs) might exert their therapeutic effects through altering cortisol secretion. OBJECTIVE: This study assessed the effects of SSRI administration on diurnal cortisol secretion in healthy volunteers. METHODS: Sixty-four healthy men and women were randomised to receive either 10 mg escitalopram or placebo for six days in a double-blind fashion. On day six of medication, saliva samples were obtained at home for measurement of diurnal cortisol parameters (cortisol slope, cortisol awakening response, total daily cortisol output). RESULTS: Women receiving escitalopram had significantly steeper cortisol slopes across the day compared with those receiving placebo (F(1, 36) = 7.54, p = 0.009). This alteration in cortisol slope was driven by increases in waking cortisol levels (F(1, 35) = 9.21, p = 0.005). Escitalopram did not have any significant effect on the cortisol awakening response or the total daily cortisol output. CONCLUSIONS: Flattened cortisol slopes have been seen in depression. The results of this study suggest that escitalopram might exert its therapeutic effect in women in part through correction of a flattened diurnal cortisol rhythm

The mediation of coronary calcification in the association between risk scores and cardiac troponin T elevation in healthy adults: Is atherosclerosis a good prognostic precursor of coronary disease?

BACKGROUND: Conventional cardiac risk scores may not be completely accurate in predicting acute events because they only include factors associated with atherosclerosis, considered as the fundamental precursor of cardiovascular disease. In UK in 2006-2008 (Whitehall II study) we tested the ability of several risk scores to identify individuals with cardiac cell damage and assessed to what extent their estimates were mediated by the presence of atherosclerosis. METHODS: 430 disease-free, low-risk participants were tested for high-sensitivity cardiac troponin-T (HS-CTnT) and for coronary calcification using electron-beam, dual-source, computed tomography (CAC). We analysed the data cross-sectionally using ROC curves and mediation tests. RESULTS: When the risk scores were ranked according to the magnitude of ROC areas for HS-CTnT prediction, a score based only on age and gender came first (ROC area=0.79), followed by Q-Risk2 (0.76), Framingham (0.70), Joint-British-Societies (0.69) and Assign (0.68). However, when the scores were ranked according to the extent of mediation by CAC (proportion of association mediated), their order was essentially reversed (age&gender=6.8%, Q-Risk2=9.7%, Framingham=16.9%, JBS=17.8%, Assign=17.7%). Therefore, the more accurate a score is in predicting detectable HS-CTnT, the less it is mediated by CAC; i.e. the more able a score is in capturing atherosclerosis the less it is able to predict cardiac damage. The P for trend was 0.009. CONCLUSIONS: The dynamics through which cardiac cell damage is caused cannot be explained by 'classic' heart disease risk factors alone. Further research is needed to identify precursors of heart disease other than atherosclerosis

Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multicentre nation-wide cohort

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95%CI=6.3-13.1). Multiple Cox regression analysis identified 3 key predictors: age showed a positive log-linear effect (adjusted HR for 50% increase=1.2, 95%CI=1.1-1.3, P=0.005), the serum concentration of thyrotropin (TSH) showed a positive linear effect (adjusted HR for 1 mIU/L increase=1.3, 95%CI=1.1-1.4, P