Psychosocial correlates of atrial natriuretic peptide: a marker of vascular health.

BACKGROUND: Psychosocial factors have been associated with cardiovascular outcomes, but few studies have examined the association between psychosocial function and natriuretic peptides. PURPOSE: The purpose of this study is to determine the predictive value of hostility, anger, and social support in relation to atrial natriuretic peptide (ANP), a marker of vascular health, among middle-aged men. METHODS: One hundred twenty-one men (mean age = 39.8 years, SD = 4.1) underwent assessments of ANP and completed the Cook-Medley Hostility Scale, the Spielberger State-Trait Anger Scale, and the Interview Schedule for Social Interaction. RESULTS: Higher levels of hostility (ß = 0.22 [95 % CI 0.04, 0.40], P = 0.032) and trait anger (ß = 0.18 [95 % CI 0.01, 0.37], P = 0.044) were associated with greater ANP levels. In contrast, higher perceived social support was also associated with lower ANP levels, (ß = -0.19 [95 % CI -0.05, -0.41], P = 0.010). CONCLUSIONS: Psychosocial factors, including hostility, anger, and social support, are associated with varying ANP levels among middle-aged men, independent of cardiovascular and behavioral risk factors.

Usefulness of heart rate to predict cardiac events in treated patients with high-risk systemic hypertension.

A high heart rate (HR) predicts future cardiovascular events. We explored the predictive value of HR in patients with high-risk hypertension and examined whether blood pressure reduction modifies this association. The participants were 15,193 patients with hypertension enrolled in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and followed up for 5 years. The HR was assessed from electrocardiographic recordings obtained annually throughout the study period. The primary end point was the interval to cardiac events. After adjustment for confounders, the hazard ratio of the composite cardiac primary end point for a 10-beats/min of the baseline HR increment was 1.16 (95% confidence interval 1.12 to 1.20). Compared to the lowest HR quintile, the adjusted hazard ratio in the highest quintile was 1.73 (95% confidence interval 1.46 to 2.04). Compared to the pooled lower quintiles of baseline HR, the annual incidence of primary end point in the top baseline quintile was greater in each of the 5 study years (all p <0.05). The adjusted hazard ratio for the primary end point in the highest in-trial HR heart rate quintile versus the lowest quintile was 1.53 (95% confidence interval 1.26 to 1.85). The incidence of primary end points in the highest in-trial HR group compared to the pooled 4 lower quintiles was 53% greater in patients with well-controlled blood pressure (p <0.001) and 34% greater in those with uncontrolled blood pressure (p = 0.002). In conclusion, an increased HR is a long-term predictor of cardiovascular events in patients with high-risk hypertension. This effect was not modified by good blood pressure control. It is not yet known whether a therapeutic reduction of HR would improve cardiovascular prognosis.

Predicting arterial stiffness with ambulatory blood pressure: an 11-year follow-up.

No prospective data have been published on whether ambulatory blood pressure (BP) works better than casual measurements in predicting arterial stiffness. This study with 11-year follow-up was launched to evaluate the usefulness of ambulatory intra-arterial BP in predicting pulse wave velocity (PWV). Ninety-seven previously healthy men were recruited from a routine physical check-up at baseline. BP was measured with standard cuff and intra-arterial ambulatory methods. Sixty-seven subjects with no antihypertensive medication were enrolled for a visit after a follow-up of 11 years. Arterial stiffness was estimated with PWV derived with impedance cardiography. Ambulatory 24-h systolic blood pressure (SBP) (r = 0.30, P = 0.01), 24-h mean arterial pressure (r = 0.27, P = 0.03), 24-h pulse pressure (r = 0.27, P = 0.03) and daytime SBP (r = 0.26, P = 0.03) were the best BP variables in predicting future PWV. Casual BP values did not bear significant correlations with future PWV. In hierarchical regression analysis, the best predictive value for future PWV was achieved with the model including ambulatory 24-h SBP, smoking (number of cigarettes) and age (adjusted R(2) = 0.26). In conclusion, to our knowledge, this is the only prospective follow-up study to show that ambulatory BP is superior to casual BP measurement in predicting future PWV.

Metabolic syndrome and arterial stiffness: the Health 2000 Survey.

Metabolic syndrome and its components have been associated with arterial stiffness and cardiovascular disease. The objective of this study was to examine the independent influences of metabolic syndrome, its components, and other cardiovascular risk factors on arterial stiffness as well as to compare 2 definitions for metabolic syndrome (National Cholesterol Education Program [NCEP] and International Diabetes Federation [IDF]) in their ability to identify subjects with arterial stiffness. The study population consisted of 401 Finnish men and women aged 45 years and older who participated in a substudy of the Finnish population-based Health 2000 Survey. Pulse wave velocity (PWV) measured by whole-body impedance cardiography was used as a marker of elevated arterial stiffness. In multivariate models, systolic blood pressure, age, waist circumference, and fasting blood glucose (P < or = .001 for all) were independent determinants for PWV. In the models including metabolic syndrome instead of its components, the NCEP and IDF definitions were similarly associated with PWV (P < or = .01 for both), the other independent determinants being age, sex (P < .001 for both) and plasma C-reactive protein concentration (P = .016 and P = .005 in models containing the NCEP and IDF definitions, respectively). Systolic blood pressure, age, waist circumference, and fasting blood glucose level were independently associated with increased arterial stiffness. Metabolic syndrome determined increased arterial stiffness independently of other known cardiovascular risk factors. The NCEP and IDF definitions did not differ in their ability to identify subjects with increased arterial stiffness.

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy.

In the main Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) report, we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens. In this report, we analyzed outcomes in 7080 patients (46.4%) who, at the end of the initial drug adjustment period (6 months), remained on monotherapy. Baseline characteristics were similar in the valsartan (N=3263) and amlodipine (N=3817) groups. Time on monotherapy was 3.2 years (78% of treatment exposure time). The average in-trial blood pressure was similar in both groups. Event rates in the monotherapy group were 16% to 39% lower than in the main VALUE trial. In the first analysis, we censored patients when they discontinued monotherapy ("censored"); in the second, we counted events regardless of subsequent therapy (intention-to-treat principle). We also assessed the impact of duration of monotherapy on outcomes. No difference was found in primary composite cardiac end points, strokes, myocardial infarctions, and all-cause deaths with both analyses. Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses (hazard ratios: 0.63, P=0.004 and 0.78, P=0.045, respectively). Longer duration of monotherapy amplified between-group differences in heart failure. New-onset diabetes was lower in the valsartan group with both analyses (odds ratios: 0.78, P=0.012 and 0.82, P=0.034). Thus, despite lower absolute event rates in monotherapy patients, the relative risks of heart failure and new-onset diabetes favored valsartan. Moreover, these findings support the feasibility of comparative prospective trials in lower-risk hypertensive patients.

Asymmetric dimethylarginine and hemodynamic regulation in middle-aged men.

The goal of this study was to evaluate the role of asymmetric dimethylarginine (ADMA) in the regulation of hemodynamic functions in hypertensive men. It has been suggested that ADMA, as an endogenous nitric oxide synthase inhibitor, is linked to hypertension and vascular reactivity. Sixty-seven men aged 51.1 years (range, 45-55 years) were studied. Plasma ADMA and symmetric dimethylarginine were determined by high-performance liquid chromatography-tandem mass spectrometry. Blood pressure (BP) was measured by 24-hour ambulatory recordings and casual measurements. Hemodynamic regulation was assessed by noninvasive methods. The nitric oxide production was estimated based on plasma nitrate (NO(3)(-)) determination. Results showed that plasma arginine derivatives or l-arginine/ADMA ratio was not associated with BP values observed during 24-hour monitoring or in casual measurements. Systemic vascular resistance, pulse wave velocity, or cardiac output was not associated with plasma ADMA or plasma NO(3)(-) levels. No association was found between plasma ADMA and NO(3)(-) either. Interestingly, subjects on antihypertensive treatment had lower plasma ADMA concentrations than nontreated subjects (0.30+/-0.08 and 0.36+/-0.11 micromol/L, respectively, P=.04) despite higher BP values. In conclusion, these results suggest that plasma ADMA does not have a determinative role in the regulation of hemodynamic functions in Finnish middle-aged men.

Impaired myocardial function in newly onset type 2 diabetes associates with arterial stiffness.

AIM: The aim of this study was to evaluate myocardial function using pulsed and color-coded tissue Doppler imaging (TDI) and vascular wall elasticity using whole-body impedance cardiography (ICG) in patients with newly diagnosed Type 2 diabetes mellitus (DM2), and to compare the measurements with those of healthy controls. METHODS: Systolic (SBP) and diastolic (DBP) blood pressure and glycosylated hemoglobin (HbA1c) were measured in 49 men (mean age 52.3+/-5.6 years, duration of DM2 1.8 years), and 15 healthy male control subjects (48.3+/-7.4 years). Mitral annular peak systolic (Svm), early (Evm), and late (Avm) diastolic velocities as well as myocardial peak systolic (Sv), early (Ev) and late diastolic (Av) velocity from middle segments of the anterior, inferior and lateral wall and the inferior septum were measured by TDI. ICG at rest was used to measure cardiac index (CI) and pulse wave velocity (PWV). RESULTS: The patients had higher body mass index (BMI 29.1+/-3.7 vs. 25.2+/-2.4 kg/m(2), p=0.000) and SBP (142+/-15 vs. 120+/-7 mmHg, p=0.005) than the controls, CI was comparable (2.8+/-0.5 vs. 2.8+/-0.6l/min/m(2)). The patients had lower age adjusted myocardial Sv (3.8+/-1.1 vs. 4.8+/-1.1cm/s, p=0.002) and Ev (4.6+/-1.6 vs. 6.2+/-1.7 cm/s, p=0.011), and also mitral annulus peak early diastolic velocity (Evm 7.8+/-1.9 vs. 10.4+/-2.6 cm/s, p=0.001). In diabetic patients PWV (14.2+/-2.7 vs. 10.0+/-1.7 m/s, p=0.002) was higher. Age (r=-0.39, p=0.001), BMI (r=-0.44, p=0.000) and PWV (r=-0.52, p=0.000) correlated significantly with Evm. PWV correlated with age (r=0.50, p=0.000), SBP (r=0.67, p=0.000), and HBA1c (r=0.36, p=0.010). In stepwise regression analysis, PWV (beta=-0.39, p=0.000) was the major determinant of Evm. CONCLUSION: Myocardial function is impaired in asymptomatic patients with newly detected DM2 consistent with diabetic heart muscle disease. Arterial stiffness is strongly related to myocardial dynamics, and both may have the same pathophysiologic background.

Gender differences in the treatment and secondary prevention of CHD at population level.

OBJECTIVES: Treatment and secondary prevention measures, received by persons with coronary heart disease (CHD), are insufficiently known at the moment. The aim of this study was to investigate the state of treatment and secondary prevention of CHD in a population-based sample and to analyze possible gender differences in different age groups. DESIGN: 300 men and 300 women with CHD were identified from a nationally representative health examination survey with 88% participation rate, carried out in Finland in 2000-2001. RESULTS: Revascularization had been performed on 34% (95% confidence interval 29, 40%) of men and 13% (8, 18%) of women. Moreover, 76% (71, 81%) of the men and 63% (57, 69%) of the women used antithrombotic medications. Two thirds of both men and women used beta-blockers and one third lipid-lowering medication. Smoking was more common among men, whereas obesity and high total cholesterol concentration were more common among women. CONCLUSIONS: Secondary prevention of CHD is far from optimal and there are gender differences in the care of CHD.

Atrial fibrillation in elderly patients after cardiac surgery: postoperative hemodynamics and low postoperative serum triiodothyronine.

OBJECTIVE: The purpose of this study was to evaluate serum triiodothyronine levels as a trigger of postoperative atrial fibrillation (AF) in elderly patients undergoing cardiac surgery and to study the possible association of serum triiodothyronine levels with preoperative and postoperative hemodynamics. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Forty-six consecutive nonemergency patients 65 years or older undergoing cardiac surgery during 1999 to 2000 in Tampere University Hospital, Tampere, Finland. INTERVENTIONS: Free serum T3 concentration was used as a measure of serum triiodothyronine levels. Samples were taken preoperatively, on the fourth postoperative day, and at the 3-month follow-up. The hemodynamic state of the patients was estimated by whole-body impedance cardiography preoperatively, during the intensive care unit period, daily until the fourth postoperative day, and at the 3-month follow-up. MEASUREMENTS AND MAIN RESULTS: AF occurred in 43% of the patients. The patients in the AF group had significantly more grafts (3.9 v 3.1, p = 0.02), and there was a small difference in age between the AF and non-AF groups (73 years v 69 years, p = 0.06). The free T3 concentration on the fourth postoperative day was significantly lower in the AF group (3.5 nmol/L v 4.6 nmol/L, p = 0.04). In logistic regression analysis, the independent predictors of AF were age, number of grafts, and serum free T3 concentration on the fourth postoperative day. In the group with low T3 concentration, the cardiac index was lower (1.4 v 1.8, p = 0.05) and the systemic vascular resistance index was higher (4,064 v 2,969, p = 0.04) but only immediately after the operation. Although the AF mostly appeared during the second to fourth postoperative days, there were no longer any differences in the hemodynamic state at that time. CONCLUSIONS: In a group of elderly patients undergoing cardiac surgery, there was a strong association between a postoperative decrease of serum triiodothyronine levels and atrial fibrillation. The decrease of serum triiodothyronine levels was related to the changes of hemodynamic parameters only in the immediate postoperative period.

Comparison of treatment benefit and outcome in women versus men with chronic heart failure (from the Valsartan Heart Failure Trial).

The comparison of treatment effect and co-morbidity between the genders in the Valsartan Heart Failure Trial showed equal benefit of treatment in men and women. Co-morbidities, such as diabetes and coronary artery disease, increased nonfatal cardiac morbidity more in women than in men.

Psychological stress tasks in the prediction of blood pressure level and need for antihypertensive medication: 9-12 years of follow-up.

Increased blood pressure (BP) reactivity to subtypes of psychological stimuli may differentially predict the development of future BP elevation or hypertension. The authors present the 9-12-year follow-up results of 82 (86%) of 95 male participants with different BP levels. They were healthy, untreated, and age-matched volunteers from a routine health checkup carried out on all 35-, 40-, and 45-year-olds from a medium-sized city. Intra-arterial systolic blood pressure (SBP) during the psychological tasks improved the prediction of future casual SBP and noninvasive 24-hr ambulatory SBP compared with predictions from casual diagnostic measurements. Diastolic blood pressure (DBP) was very useful when added to casual DBP in predicting the need for antihypertensive medication. Reactivity to active tasks especially predicts the need for antihypertensive medication.

Comparison of patients with acute coronary syndrome with and without systemic hypertension.

The role of systemic hypertension in acute coronary syndrome (ACS) has not been well studied. We studied consecutive subjects admitted to the University of Michigan Health System (Ann Arbor, Michigan) with symptoms of ACS. Data were collected using a standardized form. This observational study is currently ongoing; we collected data from May 1999 to December 2000 for 979 subjects, 890 of whom also had 6-month follow-up data. Hypertensives represented 64.4% (n = 630) of the total population. In general, hypertensive patients were older than normotensives (66.3 vs 59.9 years, p <0.0001), more often women (38.7% vs 26.9%, p = 0.0002), and had more comorbidities, such as previous myocardial infarction (47.9% vs 33.8%, p <0.0001), congestive heart failure (25.7% vs 12.0%, p <0.0001), and diabetes (36.9% vs 17.8%, p <0.0001). At admission, hypertensives had higher systolic blood pressure. Hypertensives had fewer electrocardiographic abnormalities indicating ischemic changes (67.9% vs 76.3%, p = 0.01) and had fewer incident of acute myocardial infarction (AMI) (70.7% vs 76.1%, p = 0.07) than normotensives. There was consistency over different levels of admission systolic blood pressure. Hypertensives received more oral cardiovascular drugs, and had undergone more invasive procedures. The lower rate of AMI in hypertensives seemed to be related to the higher frequency of a history of percutaneous coronary intervention and coronary artery bypass grafting. However, at 6-month follow-up, age- and gender-adjusted odds ratios for adverse events were equivalent in hypertensives and normotensives, suggesting no continuing differential treatment benefit for hypertensives in the months after the initial ACS episode.

Pulse pressure responses to psychological tasks improve the prediction of left ventricular mass: 10 years of follow-up.

OBJECTIVES: To examine the role of casual blood pressure measurements and blood pressure responses to psychological tasks in the prediction of future left ventricular mass index (LVMI), and to determine the importance of different components of blood pressure, and the predictive value of an individual's personal characteristics and antihypertensive medication on future LVMI. METHODS: At baseline, blood pressure was recorded by casual measurements; during tests it was recorded by intra-arterial monitoring. The participants were healthy, untreated 35-45-year old men. Echocardiography data both at baseline and after 10 years of follow-up were available from 65 individuals, of whom 49 (75%) were not taking antihypertensive medication at follow-up. Those not taking antihypertensive medication were included in the prediction of LVMI (g/m2). RESULTS: Baseline LVMI correlated significantly with future LVMI only among the 49 unmedicated individuals (r = 0.52, P < 0.0001). The predictive value of baseline LVMI on future LVMI among them (adjusted coefficient of determination = 0.26) was not improved by the inclusion of casual blood pressure. In contrast, blood pressure responses to the psychological tasks improved the prediction of future LVMI by 4-13%. Pulse pressure was the blood pressure variable that entered the final prediction models; the correlations with future LVMI were best for pulse pressure response to habituation task (r = 0.43, P < 0.05) and to relaxation (r = 0.37, P < 0.05). CONCLUSIONS: To our knowledge, this is the longest prospective follow-up to show that blood pressure responses to psychological tasks improve the prediction of LVMI compared with casual blood pressure measurements. The pulse pressure, which reflects the properties of the arterial wall, is the most significant blood pressure variable in predicting future LVMI.

A "gender blind" relationship of lean body mass and blood pressure in the Tecumseh study.

BACKGROUND: Body size correlates positively with blood pressure (BP) but there is controversy about the roles of obesity versus muscularity in this relationship. METHODS: We examined the BP relationship with overweight, lean body mass (LBM), and muscle performance in 231 adolescents (17.25 +/- 3.07 years, 123 males). The skinfold thickness (SKINT) was used to measure overweight, as this was a growing population. RESULTS: Maximal foot torque, a measure of muscle strength, correlated strongly (r = 0.51, P < .001) to LBM attesting to the validity of the calculated LBM. Anthropometric measurements were available also in 944 adults (29.9 +/- 5.5 years, 461 men). Correlations of LBM to systolic (adolescents r = 0.52, adults r = 0.19, both P < .001) and diastolic (adolescents r = 0.47, adults r = 0.20, both P < .001) BP were highly significant. SKINT also correlated significantly to systolic and diastolic BP in adolescents and in adults, respectively. In both genders and populations an increasing SKINT was associated with a similar increase in BP, but this effect was superimposed on an average 10 mm Hg between-gender BP difference. The LBM in both groups and genders related to the BP in an identical fashion; the men were on the high and the women on the low end of the same BP/LBM correlation line. Thus, the amount of LBM erased categoric BP differences between the genders. CONCLUSIONS: The gender-related BP differences appear to reflect the inherent gender differences in muscle bulk.

Atrial fibrillation after coronary surgery: comparison between different health care systems.

AIMS: No studies have evaluated the influence of management strategies in different health insurance environments on atrial fibrillation (AF). This observational study compared the incidence of and treatment strategies for postoperative AF after primary coronary bypass surgery. METHODS AND RESULTS: One insurance and one public funded location was compared: University of Michigan Health Center (USA, n=272) and Tampere University Hospital (Finland, n=314). USA patients had more co-morbidities and were treated more aggressively after acute myocardial infarction. More Finns were on beta-blockers both preoperatively (93 vs. 68%, P<0.001) and postoperatively (97 vs. 66%, P<0.001). However, AF was more frequent among Finns (38 vs. 29%, P=0.037) and present on 4.6% of cases when transferred postoperatively. No USA patients had AF at time of discharge. Mean length of stay was 8.6 days at USA, and not affected by AF. The incidence of in-hospital death, strokes and multiorgan failures was similar. Multivariable analysis, adjusted for site and selection biases (propensity analysis) revealed increasing age [OR=1.063 (1.042, 1.084), P<0.0001] and use of radial arteries [OR=2.175 (1.071, 4.417), P=0.032) to be independent predictors to the incidence of postoperative AF. CONCLUSIONS: We found several major differences in patient selection and treatment strategies among primary coronary bypass patients managed in the two institutions. Despite the marked practice variation, the incidence of postoperative AF was rather similar. Despite routine use of beta-blockers, AF occurred in 29-38% of patients. However, the length of stay was not particularly affected by postoperative AF.