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1.  Cortisol Responses to Mental Stress and the Progression of Coronary Artery Calcification in Healthy Men and Women 
PLoS ONE  2012;7(2):e31356.
Psychosocial stress is a risk factor for coronary heart disease (CHD). The mechanisms are incompletely understood, although dysfunction of the hypothalamic pituitary adrenal (HPA) axis might be involved. We examined the association between cortisol responses to laboratory-induced mental stress and the progression of coronary artery calcification (CAC).
Methods and Results
Participants were 466 healthy men and women (mean age = 62.7±5.6 yrs), without history or objective signs of CHD, drawn from the Whitehall II epidemiological cohort. At the baseline assessment salivary cortisol was measured in response to mental stressors, consisting of a 5-min Stroop task and a 5-min mirror tracing task. CAC was measured at baseline and at 3 years follow up using electron beam computed tomography. CAC progression was defined as an increase >10 Agatston units between baseline and follow up. 38.2% of the sample demonstrated CAC progression over the 3 years follow up. There was considerable variation in the cortisol stress response, with approximately 40% of the sample responding to the stress tasks with an increase in cortisol of at least 1 mmol/l. There was an association between cortisol stress reactivity (per SD) and CAC progression (odds ratio = 1.27, 95% CI, 1.02–1.60) after adjustments for age, sex, pre-stress cortisol, employment grade, smoking, resting systolic BP, fibrinogen, body mass index, and use of statins. There was no association between systolic blood pressure reactivity and CAC progression (odds ratio per SD increase = 1.03, 95% CI, 0.85–1.24). Other independent predictors of CAC progression included age, male sex, smoking, resting systolic blood pressure, and fibrinogen.
Results demonstrate an association between heightened cortisol reactivity to stress and CAC progression. These data support the notion that cortisol reactivity, an index of HPA function, is one of the possible mechanisms through which psychosocial stress may influence the risk of CHD.
PMCID: PMC3273460  PMID: 22328931
2.  Influence of myocardial ischemia on outcomes in patients with systolic versus non-systolic heart failure 
Background: Heart failure (HF) is a leading cause of adult hospitalization, morbidity, and mortality. We evaluated the influence of myocardial ischemia and left ventricular ejection fraction (LVEF) on outcomes in patients who were hospitalized with new onset HF. Methods: We prospectively recruited 201 consecutive patients hospitalized for a first episode of HF from 17 medical centers across Europe and North America. All patients received gated single-photon emission computed tomographic testing with standardized study interpretations by trained core laboratory investigators. Predefined data from routine care were collected and aggregated. Computerized scoring was performed at the core laboratory and participants with a summed difference score ≥4 were defined as having myocardial ischemia. Participants were categorized as having systolic heart failure (SHF) (LVEF<40%) or nonsystolic heart failure (NS-HF) (LVEF≥40%). A proportional hazards model was used to assess the impact of clinical predictors on the outcomes of mortality, cardiac rehospitalization and a combined outcome within 2 years of study enrollment. Results: 180 patients (mean age was 65.5 ± 14.6 years and 57.2% male) fulfilled study criteria and were included. Myocardial ischemia was present in 45 (41.2%) patients with SHF and 19 (27.5%) patients with NS-HF (p <0.01). During the follow-up period, 11.1% (n=20) died and 42.2% (n=76) experienced a recurrent hospitalization. Patients with NS-HF and ischemia had the highest (73.7%) event rate compared with the other cohorts (multivariate OR=3.29, 95% CI 1.69-6.42, p=0.001). Conclusions: In new-onset HF, those with NS-HF and myocardial ischemia are at the highest risk for poor outcomes.
PMCID: PMC3253494  PMID: 22254196
Heart failure; new onset heart failure; myocardial ischemia; recurrent hospitalizations; outcomes
3.  Persistent cognitive depressive symptoms are associated with coronary artery calcification 
Atherosclerosis  2010;210(1):209-213.
The association between depression and sub-clinical atherosclerosis remains unclear. By assessing depressive symptoms only at one point in time, most previous studies have failed to ascertain long-term exposure. We examined the association of long-term depressive symptoms assessed at three time points (over 10 yrs) with a marker of sub-clinical atherosclerosis.
Participants included 454 healthy, non-medicated men and women from the Whitehall II epidemiological cohort without known cardiovascular disease (CVD). Depressive symptoms were assessed at three time points (over 10 yrs) and coronary atherosclerosis was assessed at follow-up in terms of coronary artery calcification (CAC).
18.9% of the sample reported depressive symptoms at least once during follow-up. Participants that were persistently depressed had over a two-fold increased risk of detectable CAC (Agatston score > 0) (odds ratio [OR] = 2.56, 95% CI, 1.14–5.78) and high CAC (Agatston score ≥ 100) (OR = 2.36, 1.04–5.35) compared with never depressed after adjustment for age, sex, and a range of conventional cardiac risk factors. These associations were more robust in men. Participants who were depressed on only one occasion were not at elevated risk of CAC.
Persistent cognitive symptoms of depression assessed over several time points, but not on a single occasion, are related to sub-clinical coronary atherosclerosis in men free of known CVD and diabetes.
PMCID: PMC2877780  PMID: 20153471
4.  Walking speed and subclinical atherosclerosis in healthy older adults: the Whitehall II study 
Heart  2010;96(5):380-384.
Extended walking speed is a predictor of incident cardiovascular disease (CVD) in older individuals, but the ability of an objective short-distance walking speed test to stratify the severity of preclinical conditions remains unclear. This study examined whether performance in an 8-ft walking speed test is associated with metabolic risk factors and subclinical atherosclerosis.
Epidemiological cohort.
530 adults (aged 63±6 years, 50.3% male) from the Whitehall II cohort study with no known history or objective signs of CVD.
Main outcome
Electron beam computed tomography and ultrasound was used to assess the presence and extent of coronary artery calcification (CAC) and carotid intima-media thickness (IMT), respectively.
High levels of CAC (Agatston score >100) were detected in 24% of the sample; the mean IMT was 0.75 mm (SD 0.15). Participants with no detectable CAC completed the walking course 0.16 s (95% CI 0.04 to 0.28) faster than those with CAC ≥400. Objectively assessed, but not self-reported, faster walking speed was associated with a lower risk of high CAC (odds ratio 0.62, 95% CI 0.40 to 0.96) and lower IMT (β=−0.04, 95% CI −0.01 to −0.07 mm) in comparison with the slowest walkers (bottom third), after adjusting for conventional risk factors. Faster walking speed was also associated with lower adiposity, C-reactive protein and low-density lipoprotein cholesterol.
Short-distance walking speed is associated with metabolic risk and subclinical atherosclerosis in older adults without overt CVD. These data suggest that a non-aerobically challenging walking test reflects the presence of underlying vascular disease.
PMCID: PMC2921267  PMID: 19955091
Ageing; atherosclerosis; computed tomography scanning; epidemiology; exercise testing; gait speed; imaging; physical function; risk stratification
5.  Socioeconomic Status and Subclinical Coronary Disease in the Whitehall II Epidemiological Study 
PLoS ONE  2010;5(1):e8874.
There are pronounced socioeconomic disparities in coronary heart disease, but the extent to which these primarily reflect gradients in underlying coronary artery disease severity or in the clinical manifestation of advanced disease is uncertain. We measured the relationship between socioeconomic status (SES) as indexed by grade of employment and coronary artery calcification (CAC) in the Whitehall II epidemiological cohort, and tested the contribution of lifestyle, biological and psychosocial factors in accounting for this association.
Methods and Findings
CAC was assessed in 528 asymptomatic men and women aged 53–76 years, stratified into higher, intermediate and lower by grade of employment groups. Lifestyle (smoking, body mass index, alcohol consumption, physical activity), biological (blood pressure, lipids, fasting glucose, inflammatory markers) and psychosocial factors (work stress, financial strain, social support, depression, hostility, optimism) were also measured. Detectable CAC was present in 293 participants (55.5%). The presence of calcification was related to lifestyle and biological risk factors, but not to grade of employment. But among individuals with detectable calcification, the severity of CAC was inversely associated with grade of employment (p = 0.010), and this relationship remained after controlling for demographic, lifestyle, biological and psychosocial factors. Compared with the higher grade group, there was a mean increase in log Agatston scores of 0.783 (95% C.I. 0.265–1.302, p = 0.003) in the intermediate and 0.941 (C.I. 0.226–1.657, p = 0.010) in the lower grade of employment groups, after adjustment for demographic, lifestyle, biological and psychosocial factors.
Low grade of employment did not predict the presence of calcification in this cohort, but was related to the severity of CAC. These findings suggest that lower SES may be particularly relevant at advanced stages of subclinical coronary artery disease, when calcification has developed.
PMCID: PMC2810334  PMID: 20111604
6.  Finding the age of the patient's heart 
BMJ : British Medical Journal  2003;326(7398):1045-1046.
PMCID: PMC1125972  PMID: 12750180

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