Anastasia Georgiades

Serum Heat Shock Protein 70 Levels Predict the Development of Atherosclerosis in Subjects With Established Hypertension

Abstract—Although heat shock proteins (Hsp’s) are present in the sera of healthy individuals and at elevated levels in subjects with early cardiovascular disease, their physiologic role in and value for predicting the development and/or progression of atherosclerosis have not been evaluated. Serum was obtained from 218 subjects with established hypertension (diastolic pressure >95 mm Hg) before their enrollment in the European Lacidipine Study on Atherosclerosis. Hsp60 and Hsp70, and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. As an indicator of the presence/progression of atherosclerosis, the means of the maximum intima-media (I-M) thicknesses in the far walls of common carotid arteries and bifurcations (CBMmax) were determined by ultrasonography at the time of enrollment and 4 years afterward. Increases in I-M thicknesses at follow-up were less prevalent in subjects having high serum Hsp70 levels (75th percentile) at the time of enrollment (odds ratio, 0.42; 95% confidence interval [CI], 0.22 to 0.8, P =0.008). Although a similar trend was observed for serum Hsp60 levels, this was not statistically significant (odds ratio, 0.6; 95% CI, 0.32 to 1.11, P =0.10). There was no relation between anti-Hsp antibody levels and changes in I-M thicknesses. The relation between Hsp70 levels and changes in I-M thickness was independent of age, atenolol or lacidipine treatment, smoking habits, and blood lipid levels. These findings indicate that circulating Hsp70 levels predict the development of atherosclerosis in subjects with established hypertension, and an intriguing possibility is that Hsp70 protects against or modifies the progression of atherosclerosis in this subject group.

Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease.

Poor subjective well-being has been associated with increased coronary heart disease (CHD) morbidity and mortality in population-based studies and with adverse outcomes in existing CHD. Little is known about the mechanisms responsible for this association, but immune activity appears to be a potential pathway. Despite the growing evidence linking immune activity to subjective feelings, very few studies have examined patients with CHD, and the results are conflicting. We examined consecutive women patients hospitalized for acute myocardial infarction, and/or underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. We assessed depression, vital exhaustion, and self-rated health by questionnaires. Circulating levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) concentrations were determined. After controlling for potential confounding factors there was a significant positive correlation between IL-6 levels and vital exhaustion and poor self-rated health. The association between hsCRP and vital exhaustion and self-rated health was borderline significant. In contrast, the correlations between psychological factors and IL-1ra levels were weak and non-significant, as were the correlations between inflammatory markers and depression. Similar relationships between the inflammatory markers and the measures of psychological well-being were obtained when the latter ones were categorized into tertiles. In conclusion, inflammatory activity, assessed by IL-6 and hsCRP levels, was associated with vital exhaustion and self-rated health in CHD women. These findings may provide further evidence for a possible psychoneuroimmune link between subjective well-being and CHD. Our observations also raise the possibility that a cytokine-induced sickness response in CHD may be better represented by constructs of vital exhaustion and self-rated health than of depression.

Changes in depressive symptoms and glycemic control in diabetes mellitus.

Objective: To investigate if changes in depressive symptoms would be associated with changes in glycemic control over a 12-month period in patients with Type 1 and Type 2 diabetes. Methods: Ninety (Type 1 diabetes, n = 28; Type 2 diabetes, n = 62) patients having Beck Depression Inventory (BDI) levels of >10 were enrolled in the study. Of those 90 patients, 65 patients completed a 12-week cognitive behavioral therapy intervention. BDI was assessed at baseline and thereafter biweekly during 12 months. Hemoglobin (HbA1c) and fasting blood glucose levels were assessed at baseline and at four quarterly in-hospital follow-up visits. Linear mixed-model analysis was applied to determine the effects of time and diabetes type on depressive symptoms, HbA1c levels, and fasting glucose levels. Results: Mean and standard deviation baseline BDI and HbA1c levels were 17.9 ± 5.8 and 7.6 ± 1.6, respectively, with no significant difference between patients with Type 1 and Type 2 diabetes. Mixed-model regression analysis found no difference between the groups with Type 1 and Type 2 diabetes in the within-subject effect of BDI score on HbA1c or fasting glucose levels during the study. Depressive symptoms decreased significantly (p = .0001) and similarly over a 12-month period in both patients with Type 1 and Type 2 diabetes, whereas HbA1c and fasting glucose levels did not change significantly over time in either group. Conclusion: Changes in depressive symptoms were not associated with changes in HbA1c or fasting glucose levels over a 1-year period in either patients with Type 1 or Type 2 diabetes. CBT = cognitive behavioral therapy; BDI = Beck Depression Inventory; BMI = body mass index; HAM-D = Hamilton depression scale.

Effects of Exercise and Weight Loss on Mental Stress–Induced Cardiovascular Responses in Individuals With High Blood Pressure

The purpose of this study was to determine the effects of exercise and weight loss on cardiovascular responses during mental stress in mildly to moderately overweight patients with elevated blood pressure. Ninety-nine men and women with high normal or unmedicated stage 1 to stage 2 hypertension (systolic blood pressure 130 to 179 mm Hg, diastolic blood pressure 85 to 109 mm Hg) underwent a battery of mental stress tests, including simulated public speaking, anger recall interview, mirror trace, and cold pressor, before and after a 6-month treatment program. Subjects were randomly assigned to 1 of 3 treatments: (1) aerobic exercise, (2) weight management combining aerobic exercise with a behavioral weight loss program, or (3) waiting list control group. After 6 months, compared with control subjects, participants in both active treatment groups had lower levels of systolic blood pressure, diastolic blood pressure, total peripheral resistance, and heart rate at rest and during mental stress. Compared with subjects in the control group, subjects in the exercise and weight management groups also had greater resting stroke volume and cardiac output. Diastolic blood pressure was lower for the weight management group than for the exercise-only group during all mental stress tasks. These results demonstrate that exercise, particularly when combined with a weight loss program, can lower both resting and stress-induced blood pressure levels and produce a favorable hemodynamic pattern resembling that targeted for antihypertensive therapy.

Inflammatory markers and heart rate variability in women with coronary heart disease.

Purpose.  Both heart rate variability (HRV) and inflammatory markers are carrying prognostic information in coronary heart disease (CHD), however, we know of no studies examining their relation in CHD. The aim of this study, therefore, was to assess the association between HRV and inflammatory activity, as reflected by the levels of interleukin‐6 (IL‐6), IL‐1 receptor antagonist (IL‐1ra) and C‐reactive protein (CRP).

Biobehavioral Approaches to the Treatment of Essential Hypertension

Despite recent advances in the medical management of hypertension, chronically elevated blood pressure remains a major health problem in the United States, affecting almost 50 million Americans. It is widely recognized that lifestyle factors contribute to the development and maintenance of elevated blood pressure. This article critically reviews current approaches to the nonpharmacological treatment of high blood pressure and highlights outcome studies of exercise, weight loss and dietary modification, and stress management and relaxation therapies. Methodological issues in the assessment and treatment of hypertension are discussed, along with possible mechanisms by which lifestyle modification may reduce elevated blood pressure.

Financial strain predicts recurrent events among women with coronary artery disease

BACKGROUND Although a number of epidemiological studies have found an association between socioeconomic status (SES) indices such as income and education and coronary morbidity and mortality, few have looked at health consequences arising from actually experiencing financial shortcomings. The objective of the present study was to examine whether financial strain predicts recurrent coronary artery disease (CAD) events among women with established CAD. METHODS Two hundred two women (mean age 62+/-9 years) hospitalized for an acute coronary event were followed over a period of 3.5 years. Demographic, socioeconomic, lifestyle-related, psychosocial and biological characteristics were obtained by means of questionnaires and clinical examination. Data on recurrent cardiac events were collected from the Swedish discharge and death registers. RESULTS Women experiencing financial strain over the past year had an increased risk for recurrent events, i.e. the combination of all-cause mortality, new acute myocardial infarction and unstable angina pectoris during the follow-up with an unadjusted hazard ratio (HR) of 3.2 (95% CI 1.6-6.6), and a HR of 2.76 (95% CI 1.02-7.50) after controlling for education, household income, age, cohabiting status, inclusion diagnosis and rehabilitation therapy. Adjustment for potential mediators, i.e. psychosocial factors, lipids, diabetes mellitus, smoking, body-mass index, blood pressure, physical activity, alcohol consumption, participation in other cardiac rehabilitation programs did not alter the results significantly. CONCLUSIONS Financial strain was a predictor for recurrent events among women with CAD, independently of commonly used SES indicators such as education and household income. Future studies will have to explore the mechanism behind this association.

Psychosocial work characteristics and perceived control in relation to cardiovascular rewind at night.

This study examined the effects of psychosocial work characteristics on cardiovascular rewind at night. Ambulatory 24-hr recordings of blood pressure (BP) and heart rate (HR) of 75 borderline hypertensive and 74 normotensive men were related to diary ratings of perceived control (PC) and to scores of psychological demand (P), control (C), and social support (S) at work determined by an occupational classification system. Multiplicative interaction terms for job strain (P x C), isostrain (P x C x S), and Job Strain x Perceived Control (P x C x PC) were calculated. The P x C x PC interaction predicted diastolic BP at night but not at work. A delayed latency to attain the lowest systolic BP during the night was found for jobs with high job strain and isostrain. Low perceived control and social support were associated with higher HR at work and at night. A logistic regression analysis indicated that the interaction between P x C x PC and the body mass index was independently associated with borderline hypertension.

Stress-induced blood pressure measurements predict left ventricular mass over three years among borderline hypertensive men

Exaggerated cardiovascular reactivity has been implicated in the development of left ventricular hypertrophy. The aim of the present study was to investigate the predictive value of casual clinic, 24‐h ambulatory blood pressure and stress‐induced blood pressure measurements in the laboratory for left ventricular structures over a 3‐year period in a group of middle‐aged borderline hypertensive men. The stress test included a pretask resting period and two tasks, mental arithmetic and isometric muscle contraction. Left ventricular wall thickness was assessed by M‐mode echocardiography. All stress‐induced blood pressure levels and reactivity measures as well as ambulatory systolic blood pressure and mean arterial pressure levels were significantly correlated with left ventricular mass index (LVMI) 3 years later (r = 0.31–0.50), whereas there were no significant correlations between casual clinic or resting BP measurement and LVMI. A stepwise multiple regression analysis with LVMI at the 3‐year follow‐up as the dependent variable was applied. Baseline LVMI was entered as a forced variable and explained 24% of the variance in LVMI. Mean arterial blood pressure reactivity in the laboratory was the strongest additional independent variable, and added 15% to the prediction of LVMI 3 years later. Using a median split approach, the borderline hypertensive group was divided into high and low BP reactors. High and low BP reactors did not differ at initial baseline, but at the 3‐year follow‐up the high reactive group had significantly larger LVMI than the low reactive group. Results from the present study suggest that stress‐induced BP reactivity measurements predict the development of LVMI better than casual or resting BP measurements. Thus, measuring BP during standardized stress tests could be a method used to identify borderline hypertensive individuals at increased risk of developing left ventricular hypertrophy.

Atheroprotective natural anti-phosphorylcholine antibodies of IgM subclass are decreased in Swedish controls as compared to non-westernized individuals from New Guinea.

ObjectiveTo determine the importance of IgM antibodies against phosphorylcholine (aPC), a novel protective factor for cardiovascular disease (CVD), in a population with a non-western life style as compared with a Swedish control group.Methods and resultsRisk factors for cardiovascular disease were determined in a group of 108 individuals aged 40–86 years from New Guinea and 108 age-and sex-matched individuals from a population based study in Sweden. Antibodies were tested by ELISA. aPC IgM levels were significantly higher among New Guineans than among Swedish controls (p < 0.0001). This difference remained significant among both men and women when controlled for LDL and blood pressure which were lower and smoking which was more prevalent in New Guineans as compared to Swedish controls (p < 0.0001). aPC IgM was significantly and negatively associated with age and systolic blood pressure among Swedish controls and with waist circumference among New Guineans. aPC IgM levels were significantly higher among women than men in both groups. The proportion of the saturated fatty acid (FA) myristic acid in serum cholesterol esters was negatively but polyunsaturated eicosapentaenoic acid and also lipoprotein (a) were positively associated with aPC IgM levels.ConclusionIgM-antibodies against PC, which have atheroprotective properties, are higher in a population from Kitava, New Guinea with a traditional lifestyle, than in Swedish Controls, and higher among women than men in both populations tested. Such antibodies could contribute to the low incidence of cardiovascular disease reported from Kitava and could also provide an explanation as to why women have a later onset of CVD than men.