Effects of mild hypercapnia on myocardial injury after out-of-hospital cardiac arrest. A sub-study of the TAME trial.

PURPOSE: Mild hypercapnia did not improve neurological outcomes for resuscitated out-of-hospital cardiac arrest (OHCA) patients in the Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial. However, the effects of hypercapnic acidosis on myocardial injury in patients with cardiac arrest is unexplored. We investigated whether mild hypercapnia compared to normocapnia, following emergency coronary intervention, increased myocardial injury in comatose OHCA-patients with AMI. METHODS: Single-centre, prospective, pre-planned sub-study of the TAME trial. Patients were randomised to targeted mild hypercapnia (PaCO2 =6.7-7.3 kPa) or normocapnia (PaCO2 =4.7-6.0 kPa) for 24 hours. Myocardial injury was assessed with high-sensitive cardiac troponin T (hs-cTnT) measured at baseline, 24, 48 and 72 hours. Haemodynamics were assessed with right heart catheterisation and blood-gas analyses every 4th hour for 48 hours. RESULTS: We included 125 OHCA-patients. 57 (46%) had an AMI, with 31 and 26 patients randomised to hypercapnia and normocapnia, respectively. Median peak hs-cTnT in AMI-patients was 58% lower in the hypercapnia-group: 2136 (IQR: 861-4462) versus 5165 ng/L (IQR: 2773-7519), p =0.007. Lower average area under the hs-cTnT curve was observed in the hypercapnia-group: 2353 (95% CI 1388-3319) versus 4953 ng/L (95% CI 3566-6341), P-group =0.002. Hypercapnia was associated with increased cardiac power output (CPO) and lower lactate levels in patients with AMI (P-group <0.05). hs-cTnT, lactate and CPO were not significantly different between intervention groups in OHCA-patients without AMI (p >0.05). CONCLUSIONS: Mild hypercapnia was not associated with increased myocardial injury in resuscitated OHCA-patients. In AMI-patients, mild hypercapnia was associated with lower hs-cTnT and lactate, and improved cardiac performance. TRIAL REGISTRATION NUMBER: NCT03114033 Take-home-message: In this single-centre, prospective sub-study of a randomised cardiac arrest trial targeting mild hypercapnia was not associated with increased myocardial injury after out-of-hospital cardiac arrest. Compared to targeted normocapnia, mild hypercapnia was associated with lower hs-cTnT levels in patients with acute myocardial infarction as the cause of cardiac arrest.

Cardiovascular changes induced by targeted mild hypercapnia after out of hospital cardiac arrest. A sub-study of the TAME cardiac arrest trial.

AIM: Hypercapnia may elicit detrimental haemodynamic effects in critically ill patients. We aimed to investigate the consequences of targeted mild hypercapnia versus targeted normocapnia on pulmonary vascular resistance and right ventricular function in patients resuscitated from out-of-hospital cardiac arrest (OHCA). METHODS: Pre-planned, single-centre, prospective, sub-study of the Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial. Patients were randomised to mild hypercapnia (PaCO2 = 6.7-7.3 kPa) or normocapnia (PaCO2 = 4.7-6.0 kPa) for 24 hours. Haemodynamic assessment was performed with right heart catheterisation and serial blood-gas analyses every4th hour for 48 hours. RESULTS: We studied 84 patients. Mean pH was 7.24 (95% CI 7.22-7.30) and 7.32 (95% CI 7.31-7.34) with hypercapnia and normocapnia, respectively (P-group < 0.001). Pulmonary vascular resistance index (PVRI), pulmonary artery pulsatility index, and right atrial pressure did not differ between groups (P-group > 0.05). Mean cardiac index was higher with mild hypercapnia (P-group < 0.001): 2.0 (95% CI 1.85-2.1) vs 1.6 (95% CI 1.52-1.76) L/min/m2. Systemic vascular resistance index was 2579 dyne-sec/cm-5/ m2 (95% CI 2356-2830) with hypercapnia, and 3249 dyne-sec/cm-5/ m2 (95% CI 2930-3368) with normocapnia (P-group < 0.001). Stroke volumes (P-group = 0.013) and mixed venous oxygen saturation (P-group < 0.001) were higher in the hypercapnic group. CONCLUSION: In resuscitated OHCA patients, targeting mild hypercapnia did not increase PVRI or worsen right ventricular function compared to normocapnia. Mild hypercapnia comparatively improved cardiac performance and mixed venous oxygen saturation.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Exercise-induced change in circulating NT-proBNP could not distinguish between patients with and without coronary artery disease: the CADENCE study.

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.

Gut Leakage Markers in Response to Strenuous Exercise in Patients with Suspected Coronary Artery Disease.

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.

Differential associations of cardiac troponin T and cardiac troponin I with coronary artery pathology and dynamics in response to short-duration exercise.

BACKGROUND: We aimed to assess the associations between cardiac troponin (cTn) T and I concentrations, physical exercise and the presence and severity of angiographic coronary artery disease (CAD) in patients evaluated for suspected chronic coronary syndrome (CCS). METHODS AND RESULTS: All patients performed an exercise stress test on a bicycle ergometer and underwent invasive coronary angiography with weighted anatomical evaluation using the Gensini score. Blood samples were collected before and after exercise and analysed with high-sensitivity (hs) cTnT and cTnI assays. Of 297 patients (median age 62 (Quartile [Q]1-3 56-69) years, 35% female), 46% were categorized as "severe CAD" (Gensini score ≥ 20). Resting hs-cTnT and hs-cTnI concentrations were detectable in 88% and 100% of patients, with medians of 6 (Q1-3 4-9) ng/L and 1.5 (0.9-2.4) ng/L, respectively. In adjusted normalized linear regression analyses, higher resting concentrations were associated with increasing Gensini score (hs-cTnT: B 0.19, 95% Confidence Interval [CI] [0.09-0.41], p < 0.001; hs-cTnI: B 0.18, [0.06-0.30], p = 0.002). The area under the receiver operating characteristics curve for predicting severe CAD was 0.72 (95% CI [0.66-0.78]) and 0.68 (0.62-0.74) for resting hs-cTnT and hs-cTnI, p = 0.11 for difference. The median (Q1-3) relative increase in hs-cTnT and hs-cTnI concentrations were 5 (0-12) % and 13 (3-27) %, respectively, with no significant associations with CAD severity. CONCLUSIONS: In patients with suspected CCS, higher hs-cTn concentrations at rest were associated with increasing angiographic severity of CAD, without any significant differences between the troponin isotypes. Post-exercise hs-cTn concentrations did not have discriminatory power for CAD.

Markers of remodeling in subcutaneous adipose tissue are strongly associated with overweight and insulin sensitivity in healthy non-obese men.

Alteration in extracellular matrix (ECM) in adipose tissues (AT) has been associated with insulin resistance, diabetes and obesity. We investigated whether selected biomarkers of ECM remodeling in AT in healthy subjects associated with the amount and distribution of AT and with glucometabolic variables. Subcutaneous AT and fasting blood samples from 103 middle-aged healthy non-obese men were used. AT gene expression and circulating levels of the biomarkers were quantified. Distribution of AT was assessed by computed tomography, separated into subcutaneous, deep subcutaneous and visceral AT. Insulin sensitivity was measured by glucose clamp technique. Metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-1 and plasminogen activator inhibitor (PAI)-1 expression in AT correlated significantly to the amount of AT in all compartments (rs = 0.41-0.53, all p ≤ 0.01), and to insulin sensitivity, insulin, C-peptide, waist circumference and body mass index (BMI) (rs = 0.25-0.57, all p ≤ 0.05). MMP-9 was 5.3 fold higher in subjects with insulin sensitivity below median (p = 0.002) and 3.1 fold higher in subjects with BMI above median level (p = 0.013). In our healthy non-obese middle-aged population AT-expressed genes, central in remodeling of ECM, associated strongly with the amount of abdominal AT, overweight and insulin sensitivity, indicating AT-remodeling to play a role also in non-obese individuals. The remodeling process seems furthermore to associate significantly with glucometabolic disturbances.Trial registration: ClinicalTrials.gov, NCT01412554. Registered 9 August 2011, https://clinicaltrials.gov/ct2/show/NCT01412554?term=NCT01412554 .

High-sensitive cardiac Troponin T and exercise stress test for evaluation of angiographically significant coronary disease.

BACKGROUND: Exercise stress test (EST) has a moderate precision for diagnosis of CAD and could potentially obtain improved accuracy if adding a reliable cardiac biomarker to the test. OBJECTIVE: We aimed to investigate resting levels and change in hs-cTnT during EST in patients with and without angiographically significant CAD. Moreover, we intended to explore the additive value of hs-cTnT to EST results in diagnosis of stable CAD. We hypothesized that hs-cTnT would be higher in CAD patients and increase diagnostic precision of EST. METHOD: Patients presenting with symptoms of stable CAD, performed a maximal EST on a bicycle ergometer. Venous blood samples were taken at rest and within 5 min post-exercise. All patients underwent coronary angiography. Significant CAD was defined as having ≥75% stenosis in one or more segments of the coronary arteries. RESULTS: Out of the 297 participants, significant CAD was found in 111 (37%) patients. Patients with significant CAD compared to without, had higher resting levels of hs-cTnT (median 8.1 vs 5.0 ng/L) and no significant difference in exercise-induced change (median 0.5 vs 0.3 ng/L), p < 0.001 and p = 0.086 respectively. Combined resting hs-cTnT with EST had higher predictive value for significant CAD than EST alone, AUC = 0.751 vs. AUC = 0.637. In an adjusted multivariable regression analysis, resting hs-cTnT >6.0 ng/L was predictive for having significant CAD, OR 2.55 (CI 95% 1.40, 4.65 p = 0.002). CONCLUSION: In patients with suspected stable CAD, hs-cTnT has a predictive value alone, as well as added to a diagnostic EST for CAD.

Interleukin-18 and the NLR family pyrin domain containing-3 inflammasome in adipose tissue are strongly associated with glucometabolic variables in a cohort of middle-aged men.

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.

Effect of strenuous exercise on mediators of inflammation in patients with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is considered a low-grade inflammatory disease. We aimed to identify effects of short-term strenuous exercise on mediators of systemic inflammation, endothelial and platelet activation in patients with angiographically verified CAD. We hypothesized that a more pronounced inflammatory response would be present in patients with CAD than in those without CAD. METHODS: In subjects with symptoms indicative of stable CAD, an exercise stress test on a bicycle ergometer was performed. Venous blood samples, taken at rest and within 5 min after end of exercise, were analyzed for the following markers by ELISAs: TNF-α, IL-6, MCP-1, ICAM-1, VCAM-1, E-selectin, P-selectin, CD40L and RANTES. All participants underwent conventional coronary angiography. CAD was defined as having any degree of atherosclerosis. RESULTS: A total of 110 patients were included, of whom 74 were found to have CAD. Mean exercise duration was 10:06 ±â€¯3:56 min with no significant difference between the two groups. All measured markers changed significantly during exercise (p ≤ 0.012). A significantly less pronounced increase in CD40L in the CAD group than in the no CAD group was observed (p = 0.050), however, after adjustment for hematocrit this difference was no longer significant. CONCLUSION: An instant inflammatory response was observed during short-term strenuous exercise in patients with symptoms of CAD. However, the exercise mediated response was not more pronounced in patients with CAD.

Pro-coagulant activity during exercise testing in patients with coronary artery disease.

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.

Predictors of abdominal adipose tissue compartments: 18-year follow-up of young men with and without family history of diabetes.

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.

Family history of hypertension and serum triglycerides predict future insulin sensitivity: a 17-year follow-up study of young men.

OBJECTIVE: Low insulin sensitivity is closely related to both cardiovascular diseases and diabetes development. Still, correlates of insulin sensitivity have mainly been examined in cross-sectional studies. As far as we are aware, the longitudinal stability of insulin sensitivity in young men is largely unknown. We aimed for the first time to examine both the stability (tracking) and longitudinal predictors of future insulin sensitivity in healthy young men with and without a family history of diabetes or hypertension. METHODS: We performed a 17-year follow-up study of a cohort of 100 healthy young men. Cardiovascular risk markers, including insulin sensitivity measured by the gold standard method--hyperinsulinaemic isoglycaemic glucose clamp--were examined both at baseline and at follow-up. RESULTS: Baseline insulin sensitivity showed no significant correlation with insulin sensitivity at follow-up, whereas all other measured cardiovascular risk markers had significant correlation (tracking coefficients 0.4-0.7). In multiple regression analyses, family history of hypertension and baseline triglycerides remained the negative predictors of future insulin sensitivity. This was driven by the strong correlations in men with family history of diabetes. CONCLUSION: Our data suggest that clamp-derived insulin sensitivity is not a stable feature in young men, and that family history of hypertension and baseline triglycerides were associated with future insulin sensitivity, especially in men with a family history of diabetes, and irrespective of blood pressure status 17 years earlier. These findings provide further insight into the development of insulin sensitivity and related diseases.

High screening blood pressure at young age predicts future masked hypertension: A 17 year follow-up study.

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.

The prognostic significance of heart rate for cardiovascular disease and hypertension.

Five decades ago, hypertension was a debated risk factor for the development of cardiovascular disease. After further studies and the introduction of antihypertensive medications, few, if any, have doubted the important role hypertension plays as a cardiovascular risk factor. Today, a growing body of evidence emphasizes the relationship between heart rate and hypertension, and heart rate and cardiovascular disease, which makes the measurement of heart rate an important component of the cardiovascular risk assessment. Current European guidelines for managing arterial hypertension recommend the measurement of heart rate for risk stratification, but there still are no recommendations for treatment. This review discusses the evidence for a relationship between heart rate and cardiovascular mortality and morbidity and hypertension.

Long-term stability of cardiovascular and catecholamine responses to stress tests: an 18-year follow-up study.

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.

High heart rate as predictor of essential hypertension: the hyperkinetic state, evidence of prediction of hypertension, and hemodynamic transition to full hypertension.

Although essential hypertension seems to have a strong hereditary component, the triggering mechanism is unclear. It is likely that the central nervous system via autonomic sympathetic overactivation plays a key role in the development of hypertension. High heart rate has proven to be a strong predictor for cardiovascular disease and a predictor of the development of essential hypertension. Because heart rate is highly influenced by many factors such as anxiety and physical activity, it is sometimes difficult to interpret the value of heart rate measurement in individual persons. Whether heart rate itself is a risk factor for development of hypertension or just a marker for sympathetic overactivation is still a matter of debate, but the presence of elevated heart rate in both hyperkinetic and hypertensive subjects makes it an interesting and easy measurable prognostic marker.

Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study.

Insulin resistance and sympathetic activity are related by a positive feedback system. However, which precedes the other still remains unclear. The present study aimed to investigate the predictive role of sympathoadrenal activity in the development of insulin resistance in an 18-year follow-up study. We also examined whether reactivity to 2 different stress tests, a cold pressor test and a mental stress test, would differ in their predictive power. The 2 tests are supposed to represent different reactivity mechanisms: alpha- and beta-adrenergic responses, respectively. At entry, arterial plasma epinephrine and norepinephrine concentrations were measured in 99 healthy men (age, 19.3 +/- 0.4 years, mean +/- SD) during rest, a mental stress test, and a cold pressor test. Fasting plasma glucose concentration was measured at entry and at follow-up. Insulin resistance at follow-up was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Eighty subjects (81%) were eligible for follow-up after 18.0 +/- 0.9 years (mean +/- SD). The norepinephrine responses to cold pressor test at entry predicted plasma glucose concentration (r = 0.301, P = .010) and HOMA-IR (r = 0.383, P = .004) at follow-up in univariate analyses. In multiple regression analyses, corrected for fasting glucose at entry, family history of diabetes, blood pressure-lowering medication, body mass index at entry, and level of exercise, norepinephrine response to cold pressor test was found to be a positive predictor of future HOMA-IR (P = .010). This is the first long-term follow-up study in white subjects showing that sympathetic reactivity predicts future insulin resistance 18 years later. These findings may provide further insights into the pathophysiologic mechanisms of insulin resistance.

Prevention of atrial fibrillation in hypertension.

Hypertensive patients have an increased risk of developing atrial fibrillation (AF), which increases cardiovascular morbidity and mortality in this population. Primary prevention is a new strategy in treating AF; previously, it was more common to focus on preventing adverse outcomes and controlling the arrhythmia's rate and rhythm. In this review, we consider the possible preventive effects of antihypertensive treatment on new-onset AF seen in recent trials, especially with blockers of the renin-angiotensin system (RAS). Several secondary analyses of large, randomized trials regarding hypertension and heart failure have shown promising results with benefits beyond the expected blood pressure-lowering effect. A few prospective studies on prevention of AF recurrence with RAS blockade have been published, and more studies are expected to be published in the near future.

Effects on plasma noradrenaline may explain some of the improved insulin sensitivity seen by AT-1 receptor blockade.

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.