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Objective. In patients with chest pain, exercise stress test has a moderate accuracy for coronary artery disease (CAD). Adding a reliable cardiac biomarker to the exercise test could potentially improve the precision of the test. We investigated circulating NT-proBNP levels before and during exercise stress test in patients with and without angiographically verified CAD. We hypothesized that NT-proBNP would give an additive diagnostic value to the exercise stress test. Methods. In patients presenting with symptoms of stable CAD, venous blood samples were taken at rest and within 5 min of termination of a maximal stress test on a bicycle ergometer. All study participants underwent coronary angiography. Significant CAD was defined as ≥75% stenosis in one or more segments of the coronary arteries. Results. Of the 297 participants, significant CAD was found in 111 (37%) patients. Resting levels of NT-proBNP were significantly higher in patients with CAD compared with patients without CAD (74.18 vs. 56.03 ng/L), p =.005. During exercise, NT-proBNP levels increased in the total population (p <.001). The rise was, however, not significantly different between the two groups (8.24 vs. 8.51 ng/L), p =.700. Combining resting NT-proBNP with positive exercise stress test was superior to exercise test alone in predicting CAD, AUC = 0.68 vs. 0.64. Conclusion. Exercise-induced change in circulating NT-proBNP could not distinguish between patients with or without CAD. However, resting levels of NT-proBNP were significantly higher in patients with CAD than those without CAD. [ABSTRACT FROM AUTHOR]

Abstract Background Possible mechanisms behind psychophysiological hyperreactivity may be located at a cognitive-emotional level. Several personality traits have been associated with increased cardiovascular reactivity. Subjects with white coat hypertension, which may constitute a kind of hyperreactivity, are found to suppress their emotions and adapt to the surroundings to a larger extent than controls. We hypothesized in this study that a) stress reactivity is related to personality, and that b) responses to cold pressor test (CPT) and mental stress test (MST) are associated with different personality traits. Methods 87 men were selected from the 1st, 50th and 99th percentile of a blood pressure screening. Cardiovascular and catecholamine responses to MST and CPT were recorded. Fifteen personality traits were assessed using the Karolinska Scale of Personality. Possible independent explanatory predictors for cardiovascular and catecholamine variables at baseline and during stress were analyzed in multiple linear regression analyses using a stepwise forward procedure. Results Multiple regression analyses showed that muscular tension (β = 0.298, p = 0.004), irritability (β = 0.282, p = 0.016), detachment (β = 0.272, p = 0.017), psychasthenia (β = 0.234, p = 0.031) and somatic anxiety (β = 0.225, p = 0.046) were significant explanatory variables of reactivity to CPT. During MST, verbal aggression (β = -0.252, 0.031) and detachment (β = 0.253, p = 0.044) were significant predictors of norepinephrine and diastolic blood pressure response, respectively. Based on KSP-trait quartiles, delta (Δ) systolic (p = 0.025) and Δ diastolic blood pressure (p = 0.003) during MST were related to detachment score, with the highest reactivity in the 4th quartile, while Δ norepinephrine was significantly related to muscular tension (p = 0.033). Δ systolic and Δ diastolic blood pressure responses to CPT were dependent on detachment (p = 0.049 and p = 0.011, respectively) and psychasthenia (p = 0.020 and p = 0.015), while high verbal aggression was associated with lower reactivity measured by Δ norepinephrine (p = 0.037). Conclusion The present study indicates that stress reactivity is clearly related to different personality traits, without any single trait being dominant over others. Furthermore, personality seems to have as much, or even more, importance of predicting responses to CPT than responses to MST.

Background: Previous studies have indicated an association between interleukin-18 and glucose. Interleukin-18 becomes active when cleaved by caspase-1, activated by the NLR family pyrin domain containing-3 inflammasome. Aim: To investigate associations between glucometabolic variables and serum levels of interleukin-18 and genetic expression of interleukin-18, caspase-1 and NLR family pyrin domain containing-3 in adipose tissue and circulating leukocytes, and whether these mediators are related to the amount of abdominal adipose tissue . Materials and Methods: Fasting blood samples and subcutaneous adipose tissue were collected in a cohort of 103 middle-aged men. Serum levels of interleukin-18 were determined by enzyme-linked immunosorbent assay, gene expression by real-time polymerase chain reaction and insulin sensitivity by glucose clamp. The distribution of abdominal adipose tissue, separated into superficial- and deep subcutaneous, and visceral adipose tissue, was assessed by computed tomography scan. Results: Glucometabolic variables correlated significantly to serum levels of interleukin-18, and to the expression of interleukin-18 and NLR family pyrin domain containing-3 in subcutaneous adipose tissue (p < 0.05). Significant correlations were further observed between the amount of fat in the different compartments of abdominal adipose tissue and both serum levels of interleukin-18 and genetic expression of interleukin-18 and NLR family pyrin domain containing-3 in adipose tissue. Conclusion: The results implicate that the glucometabolic state is of importance for the inflammasome-related inflammation expressed both circulatory and genetically in subcutaneous adipose tissue, the latter highly reflected in the amount of abdominal adipose tissue. [ABSTRACT FROM AUTHOR]

Background: Strenuous exercise may trigger myocardial infarction through increased pro-coagulant activity. We aimed to investigate whether patients referred for exercise testing, who were found to have angiographically verified coronary artery disease (CAD), have a more hypercoagulable profile during exercise testing than those without CAD. Methods: Patients with symptoms of stable CAD were examined with exercise electrocardiography on bicycle ergometer. Venous blood samples were taken at rest and within 5 min after end of exercise. The following haemostatic variables were analyzed: tissue factor pathway inhibitor (TFPI) activity and antigen, prothrombin fragment 1 + 2 (F1 + 2), D-dimer and endogenous thrombin potential (ETP). All participants underwent conventional coronary angiography. CAD was defined as having any degree of atherosclerosis. Results: Out of the 106 patients enrolled, 70 were found to have CAD. Mean exercise duration was 10:06 ± 4:11 min, with no significant differences between the groups. A significant increase from baseline to after exercise testing was observed in all measured markers in the total population (p ≤ 0.002 for all). In patients with angiographically verified CAD, total TFPI was significantly lower at baseline compared to patients without CAD (median value 67.4 and 76.6 ng/ml respectively, p = 0.027). However, no significant differences in changes of any of the measured markers during exercise were observed between the two groups. Conclusion: Pro-coagulant activity increased during short-term strenuous exercise testing in patients with symptoms suggestive of CAD. However the hypercoagulable state observed, was not more pronounced in patients with angiographically verified CAD compared to patients without CAD. NCT01495091. [ABSTRACT FROM AUTHOR]

Objective. Approximately 10-20% of the general population have masked hypertension. However, how best to identify affected individuals is uncertain, and what predicts future masked hypertension is largely unknown. This study aimed to identify longitudinal predictors of masked hypertension. Methods. A long-term follow-up study of 100 healthy young men who had normal ( n = 28) or high ( n = 72) screening blood pressure (BP) at the compulsory military draft was carried out. They were examined in a detailed and highly standardized way for cardiovascular risk markers at baseline and at follow-up after a mean of 17.4 years. Results. At follow-up, 40% had masked hypertension. Participants with high screening BP had a 4.8 times higher likelihood of having masked hypertension at follow-up compared to men with low screening BP (odds ratio 4.8, 95% confidence interval 1.7-13.5, p = 0.003). Furthermore, only 25% of the men with masked hypertension had high normal office BP at follow-up, and the remaining 75% would, according to guidelines, not be recommended ambulatory BP measurements, and thus go undiagnosed. Conclusion. Our data suggest that high screening BP at a young age is an important predictor of future masked hypertension in young men, and that BP measurement according to guidelines is insufficient to uncover masked hypertension. [ABSTRACT FROM AUTHOR]

Cardiovascular (CV) hyperreactivity to stress must be reasonably stable if it is considered to be important in the development of hypertension and CV disease. The aim of the present study was to assess long-term stability of blood pressure, heart rate, epinephrine, and norepinephrine responses to a cold pressor test and a mental arithmetic stress test. Eighty-one subjects selected from the first (n=30), 50th (n=30), and 95th to 99th (n=39) percentiles of the mean blood pressure distribution at a military draft procedure were tested on 2 occasions 18 years apart. Stress responses were measured during a cold pressor test (hand immersed in ice water for 1 minute) and during a mental stress test (subtraction for 5 minutes). Intra-arterial blood pressure measurements and arterial catecholamine samples were taken at the initial examination. At follow-up, noninvasive Finapres beat-to-beat blood pressure measurements and venous plasma catecholamine samples were used. The 18-year correlations of the CV and epinephrine absolute responses during mental stress ranged from 0.6 to 0.8. The entry/follow-up correlation of systolic blood pressure during the mental stress test (95% CI: 0.69 to 0.86) was significantly higher than during the cold pressor test (95% CI: 0.30 to 0.65), and responses to mental stress overall appeared to be more stable than responses to the cold pressor test. Our study suggests that CV and sympathoadrenal reactivity, specifically to mental stress, are relatively stable individual characteristics. These results support one of the necessary preconditions to consider hyperreactivity involved in the development of hypertension and CV disease. [ABSTRACT FROM AUTHOR]

In the present study we hypothesized that arterial catecholamine concentrations during rest and 2 laboratory stress tests were independent predictors of blood pressure at an 18-year follow-up. At entry, blood pressure, heart rate, and arterial plasma epinephrine and norepinephrine concentrations were measured in 99 healthy men (age: 19.3+/-0.4 years, mean+/-SD) at rest, during a mental arithmetic test, and during a cold pressor test. After 18.0+/-0.9 years of follow-up, resting blood pressure was measured. The norepinephrine and epinephrine concentrations during the mental arithmetic explained 12.7% of the variation of future systolic blood pressure after adjusting for initial resting blood pressure, family history, body mass index, and systolic blood pressure during the stress test in a multiple regression analysis (adjusted R(2)=0.651; P<0.001). To conclude, the present study shows that sympathetic nervous activity during mental arithmetic predicts future blood pressure, indicating a possible causal factor in the development of essential hypertension independent of the initial blood pressure. [ABSTRACT FROM AUTHOR]

Aims. We have previously found improved insulin sensitivity in hypertensives after additional treatment with angiotensin II-receptor blocker (ARB) compared with calcium-channel blocker (CCB) alone, despite similar blood pressure lowering effects. In this study, we compare the effect of these two principal different vasodilating agents on the autonomic nervous system in the same patients, and test whether potential differences in these variables might explain the difference seen in insulin sensitivity. Methods. In a double-blind crossover study, 21 hypertensive patients were randomized to receive either 100 mg losartan (ARB) or 5 mg amlodipine (CCB) in addition to an open-labelled treatment of amlodipine 5 mg. The patients were treated for 8 weeks with either treatment regimens after a 4-week run-in and a 4-week washout period. Plasma catecholamines were measured using radioenzymatic technique and baroreflex sensitivity and heart rate variability was tested at rest and during 24-h ECG registration. Results. Plasma noradrenaline was significantly lower after additional treatment with ARB compared with CCB alone (304±29 pg/ml vs 373±43 pg/ml, p = 0.022). Heart rate variability, baroreflex sensitivity or plasma adrenaline did not differ significantly between the two treatment regimens. Conclusion. The results may suggest that improvement of insulin sensitivity by ARB is related to decreased plasma noradrenaline and potential sympatholytic effects. [ABSTRACT FROM AUTHOR]

Objective - Activation of the sympathetic nervous system may increase hematocrit (Hct), whole blood viscosity (WBV), and possibly cardiovascular risk. The aim was to study gender specific differences of mental stress on sympathetic reactivity and blood rheology. Methods - Responses in blood pressure, heart rate (HR), Hct, WBV (Bohlin rotational viscosimeter), and plasma catecholamines to a mental arithmetic stress test (MST) were measured in male (n = 10, 23 ± 3 years, BMI 23 ± 2 kg/m2) and female (n = 10, 21 ± 4 years, BMI 24 ± 2 kg/m2) students. Results - Systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR increased during MST in men and women, and declined to baseline levels after 15 min of recovery. In men, plasma adrenaline increased by 217% during MST (p < 0.01, ANOVA), and plasma noradrenaline increased by 68% (p < 0.05). Hct and WBV at low shear rates (0.5 and 1.1 l/s) increased as well (p < 0.01, p < 0.05, and p < 0.05, respectively). In women, the increase in plasma adrenaline averaged 118% during MST (p < 0.05) while plasma noradrenaline (-3%, p = 0.38), Hct, and WBV at all shear rates remained unchanged. Men and women differed in Δ adrenaline (p < 0.05), Δ noradrenaline (p = 0.01), Δ Hct (p < 0.05), and Δ WBV (p < 0.05). Δ Hct tended to correlate with Δ SBP (r = 0.60, p = 0.07), Δ DBP (r = 0.57, p = 0.09), and Δ HR (r = 0.50, p = 0.14), and correlated significantly with Δ noradrenaline (r = 0.66, p < 0.05) in men only. Multiple regression analysis showed that gender independently explained 22% of the change in Hct during mental stress. Conclusion - Data suggest gender specific differences in sympathetic and hemorrheological responses to mental stress in healthy young subjects. In men, sympathetic responses were related to hemorrheological responses, but not in women. It may be speculated whether such differences in stress responses may contribute to lower cardiovascular risk in premenopausal women than in men. [ABSTRACT FROM AUTHOR]

Elevated levels of gut leakage markers have been shown after strenuous exercise in healthy individuals. Any association between a temporary increase in these markers and the presence of coronary artery disease (CAD) is unknown. We therefore aimed to explore circulating gut leakage markers in response to a bout of strenuous exercise in patients with symptoms of CAD. Patients referred to exercise stress testing due to symptoms of CAD were included (n = 287). A maximal exercise ECG stress test was performed and venous blood samples were drawn at rest and within five minutes after, for analysis of soluble cluster of differentiation 14 (sCD14), lipopolysaccharide-binding protein (LBP), intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide (LPS) and gene expression of toll-like receptor 4 (TLR4) in circulating leukocytes. Patients then underwent coronary angiography. LPS, LBP and sCD14 increased significantly after strenuous exercise in patients with symptoms of CAD, suggesting that even short bouts of vigorous exercise are associated with gut leakage. The gene expression of TLR4 decreased significantly after exercise, possibly as a negative feedback to the increase in LPS. There were no differences in exercise-induced changes between the groups of CAD, suggesting gut leakage to be independent of the presence of CAD. [ABSTRACT FROM AUTHOR]

Background Abdominal adipose tissue (AAT) consists of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), which can be further divided into superficial and deep SAT. Despite being a key factor in the development of metabolic and cardiovascular diseases, what predicts future amount of AAT is largely unknown. Objective To determine long-term predictors of amount of AAT. Methods This was a mean 18-year follow-up study of a cohort of 94 healthy young Caucasian men, with and without a family history of diabetes (FHD). Cardiovascular risk markers were examined both at baseline and at follow-up. At follow-up, computed tomography (CT) of AAT was conducted to assess amount of superficial and deep SAT, and VAT. Results In multiple regression analyses, baseline body mass index (BMI) remained a positive predictor of future amount of superficial and deep SAT, while high-density lipoprotein (HDL) cholesterol was a negative predictor of all three sub-compartments. Baseline risk markers were generally stronger predictors among men with FHD, than among men without. In addition, FHD had greater impact on amount of deep SAT and VAT, than on amount of superficial SAT. Conclusion Our data suggest that the traditional cardiovascular risk markers BMI, HDL cholesterol and family history of diabetes are long-term predictors of the different abdominal adipose tissue compartments from young towards middle age in healthy men. In men with family history of diabetes, cardiovascular risk markers at a young age seem to be of greater importance to future amount of abdominal adipose tissue, than among men without. [ABSTRACT FROM AUTHOR]

Background: Possible mechanisms behind psychophysiological hyperreactivity may be located at a cognitive-emotional level. Several personality traits have been associated with increased cardiovascular reactivity. Subjects with white coat hypertension, which may constitute a kind of hyperreactivity, are found to suppress their emotions and adapt to the surroundings to a larger extent than controls.We hypothesized in this study that a) stress reactivity is related to personality, and that b) responses to cold pressor test (CPT) and mental stress test (MST) are associated with different personality traits., Methods: 87 men were selected from the 1st, 50th and 99th percentile of a blood pressure screening. Cardiovascular and catecholamine responses to MST and CPT were recorded. Fifteen personality traits were assessed using the Karolinska Scale of Personality. Possible independent explanatory predictors for cardiovascular and catecholamine variables at baseline and during stress were analyzed in multiple linear regression analyses using a stepwise forward procedure., Results: Multiple regression analyses showed that muscular tension (beta = 0.298, p = 0.004), irritability (beta = 0.282, p = 0.016), detachment (beta = 0.272, p = 0.017), psychasthenia (beta = 0.234, p = 0.031) and somatic anxiety (beta = 0.225, p = 0.046) were significant explanatory variables of reactivity to CPT. During MST, verbal aggression (beta = -0.252, 0.031) and detachment (beta = 0.253, p = 0.044) were significant predictors of norepinephrine and diastolic blood pressure response, respectively.Based on KSP-trait quartiles, delta (Delta) systolic (p = 0.025) and Delta diastolic blood pressure (p = 0.003) during MST were related to detachment score, with the highest reactivity in the 4th quartile, while Delta norepinephrine was significantly related to muscular tension (p = 0.033). Delta systolic and Delta diastolic blood pressure responses to CPT were dependent on detachment (p = 0.049 and p = 0.011, respectively) and psychasthenia (p = 0.020 and p = 0.015), while high verbal aggression was associated with lower reactivity measured by Delta norepinephrine (p = 0.037)., Conclusion: The present study indicates that stress reactivity is clearly related to different personality traits, without any single trait being dominant over others. Furthermore, personality seems to have as much, or even more, importance of predicting responses to CPT than responses to MST.

Atrial fibrillation is the most frequent occurring sustained cardiac arrhythmia and it is related to common cardiac disease conditions. Hypertension increases the risk of atrial fibrillation by approximately two-fold and, because of the high prevalence of hypertension, it accounts for more cases of atrial fibrillation than any other risk factor. In recent years, there are two large hypertension trials (LIFE and VALUE) and two large heart failure trials (CHARM and Val-HeFT) reporting the beneficial effect of angiotensin II-receptor blockers (ARBs) on new-onset atrial fibrillation, beyond the blood pressure-lowering effect. Blockade of the renin-angiotensin system may prevent left atrial dilatation, atrial fibrosis, dysfunction and conduction velocity slowing. Some studies also indicate direct anti-arrhythmic properties. This review aims to consider the preventive effect of ARBs on new-onset atrial fibrillation observed in recent reports from these trials, and to discuss possible mechanisms of the beneficial effect of angiotensin II-receptor blockade.

We hypothesized that resting blood pressure is related to sympathetic activity in young men who are unaware of their blood pressure status in high, normal, and low ranges and that there is a relationship between sympathetic activity and coronary risk factors. Forty-three healthy, young men from the 1st [group 1, 106/52+/-2/2 mm Hg (+/-SEM), n=15], 50th (group 2, 129/79+/-2/1 mm Hg, n=15), and 98th to 99th percentile (group 3, 166/97+/-3/1 mm Hg, n=13) at a blood pressure screening were studied with intraarterial blood pressure, heart rate, and arterial plasma catecholamine responses to a mental, cold pressor, and orthostatic stress test. At baseline, group 3 had significant higher blood pressure (137/74+/-3/2 mm Hg) than group 2 (126/66+/-3/2 mm Hg; P<0.01) and group 1 (116/62+/-2/1 mm Hg; P<0.001). Group 1 had lower systolic blood pressure than group 2 (P=0.007). Baseline epinephrine and norepinephrine showed a clear positive linear trend (P<0.05), with the lowest values being in group 1 and highest in group 3. High-density lipoprotein was negatively related to epinephrine (r=-0.387; P=0.010). Mental stress was the only test that showed significant differences in cardiovascular and sympathetic responses among the groups, where group 3 had a more pronounced response in systolic and diastolic blood pressure and heart rate compared with group 1 (P<0.001) and group 2 (P<0.01). Furthermore, we found significant positive linear trends for Deltacatecholamines during mental stress across the groups (Deltaepinephrine P=0.001 and Deltanorepinephrine P=0.026, ANOVA). We conclude that resting blood pressure reflects both variation in resting arterial catecholamines and variation in cardiovascular and sympathetic responses specifically to mental stress.