Morten Rostrup

Association between acute hypobaric hypoxia and activation of coagulation in human beings

The risk of venous thrombosis is thought to be increased by flying. In a study of 20 healthy male volunteers who were suddenly exposed to a hypobaric environment similar to that encountered within aeroplane cabins, markers of activated coagulation transiently Increased by two-fold to eight-fold. We suggest that hypobaric hypoxia, with sedentariness and dehydration, may cause this increased risk of venous thrombosis.

Adjusted Drug Treatment Is Superior to Renal Sympathetic Denervation in Patients With True Treatment-Resistant Hypertension

&NA; We aimed to investigate for the first time the blood pressure (BP)–lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (P=0.42 and P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516

Sympathoadrenal Stress Reactivity Is a Predictor of Future Blood Pressure: An 18-Year Follow-Up Study

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 R2=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.

Skin conductance correlates with perioperative stress

Background: Skin conductance (SC) as a measure of emotional state or arousal may be a tool for monitoring surgical stress in anaesthesia. When an outgoing sympathetic nervous burst occurs to the skin, the palmar and plantar sweat glands are filled up, and the SC increases before the sweat is removed and the SC decreases. This creates a SC fluctuation. The purpose of this study was to measure SC during laparoscopic cholecystectomy with propofol and remifentanil anesthaesia and to evaluate whether number and amplitude of SC fluctuations correlate with perioperative stress monitoring.

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.

Autonomic Function in Hypertensive and Normotensive Subjects: The Importance of Gender

Abstract—Baroreceptor reflex sensitivity (BRS) has been found lower and heart rate variability (HRV) parasympathetic markers have been found higher in healthy women than in healthy men. Thus, in the present study we hypothesized gender differences in the autonomic function among hypertensive subjects. Forty-one hypertensive patients and 34 normotensive subjects, age 53±1 years, were examined. Four weeks after cessation of antihypertensive therapy, HRV was assessed in 24-hour Holter ECGs, and BRS was calculated with the transfer technique. A t test was performed after log transformation of spectral values. Resting blood pressure and heart rate in the hypertensive and the normotensive groups were 150±2/100±1 (mean±SEM) and 121±2/81±1 mm Hg, respectively, and 68±1 and 60±1 bpm, respectively (P <0.0005). Compared with normotensive controls, hypertensive patients had lower total power (1224±116 versus 1797±241 ms2;P =0.03), lower low frequency power (550±57 versus 813±115 ms2;P =0.04), lower high frequency power (141±23 versus 215±38 ms2;P =0.06), lower root mean square successive difference (28.7±2.7 versus 35.7±3.0 ms;P =0.03), and PNN50 (4.9±0.6% versus 9.8±1.5%;P =0.003). BRS was also lower in the hypertensive subjects (7.6±0.6 versus 10.4±0.8 ms/mm Hg;P =0.005). When comparing the same parameters between normotensive subjects and hypertensive subjects within the same gender group, we found significant reduction (P <0.05) only within the female group. The difference in BRS within the female group was twice that within the male group. Stepwise multiple regression analysis revealed gender, age, HDL cholesterol, and blood pressure as independent explanatory variables of BRS and HRV. Our results suggest that gender is an important determinant of BRS and HRV. Autonomic function parameters were especially impaired in hypertensive women compared with hypertensive men.

Renal Sympathetic Denervation in Patients With Treatment-Resistant Hypertension After Witnessed Intake of Medication Before Qualifying Ambulatory Blood Pressure

&NA;It is unknown whether the decline in blood pressure (BP) after renal denervation (RDN) is caused by denervation itself or concomitantly improved drug adherence. We aimed to investigate the BP lowering effect of RDN in true treatment-resistant hypertension by excluding patients with poor drug adherence. Patients with resistant hypertension (n=18) were referred for a thorough clinical and laboratory work-up. Treatment-resistant hypertension was defined as office systolic BP>140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs, including a diuretic. In addition, ambulatory daytime systolic BP>135 mm Hg was required after witnessed intake of antihypertensive drugs to qualify. RDN (n=6) was performed with Symplicity Catheter System. The mean office and ambulatory BPs remained unchanged at 1, 3, and 6 months in the 6 patients, whereas there was no known change in antihypertensive medication. Two patients, however, had a fall in both office and ambulatory BPs. Our findings question whether BP falls in response to RDN in patients with true treatment-resistant hypertension. Additional research must aim to verify potential BP lowering effect and identify a priori responders to RDN before this invasive method can routinely be applied to patients with drug-resistant hypertension. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

Awareness of high blood pressure increases arterial plasma catecholamines, platelet noradrenaline and adrenergic responses to mental stress

Thirty-six, 19-year-old men within the 95th percentile of mean blood pressure (110 mmHg) at a routine medical screening were randomized into two groups and requested to return for a follow-up visit in 2 weeks. One group was sent a neutral letter, while the other was sent a letter conveying the information that their blood pressures were elevated. After 15 min sitting in the laboratory, there was a significantly higher heart rate (P less than 0.05) in the informed group. Thirteen informed and 13 uninformed subjects were examined further by intra-arterial blood pressure recording and serial sampling of arterial catecholamines during cold pressor and mental stress tests. The study was undertaken examiner-blind. Informing the subjects of high blood pressure increased both baseline plasma noradrenaline (P less than 0.01) and adrenaline (P less than 0.05) and intraplatelet noradrenaline (P less than 0.05). Blood pressure (P less than 0.05) and heart rate (P less than 0.05) increased significantly more in the informed group when the subjects were told of the cold pressor test. In addition, there were exaggerated adrenaline (P less than 0.05) and diastolic blood pressure (P less than 0.05) responses to mental stress in the informed group. Thus, awareness of high blood pressure in young men may increase sympathetic tone and responses as measured in the laboratory. Conclusions from studies on early pathogenesis of essential hypertension should therefore be drawn with more caution when patients are aware of their high blood pressure.

Insulin sensitivity, sympathetic activity, and cardiovascular reactivity in young men

The present study was undertaken to examine the relationships between insulin sensitivity, blood pressure (BP), and cardiovascular reactivity, and to assess sympathetic nervous system influence. Insulin sensitivity (GDR/I; euglycemic glucose clamp technique) was related to BP and heart rate (HR) in different situations in 40 healthy young men: in the laboratory, during a mental arithmetic stress test, and during baseline conditions at home. GDR/I correlated with supine diastolic BP in the laboratory and with maximum diastolic BP during mental stress (r = -0.46, P = .003; r = -0.62, P = .0001, respectively), but not so strongly with diastolic BP measured at home (r = -0.29, P = .09). Diastolic BP during stress and body mass index were the only independent explanatory variables of GDR/I in multiple regression analysis (multiple R = 0.71, R2 = 0.50, P < .0001). GDR/I and systolic BP were not significantly correlated at any time. GDR/I correlated negatively with HR in the laboratory and with maximum HR during mental stress, but not with HR at home. Maximum plasma epinephrine during stress correlated with stress BP and HR (r = 0.53, P = .001; r = 0.70, P < .0001, respectively) and negatively with GDR/I (r = -0.36, P < .05). In the present study, GDR/I is related to diastolic but not to systolic BP, and more closely correlated to diastolic BP and HR measured during mental stress than to diastolic BP and HR during baseline conditions at home.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of anthocyanins on cardiovascular risk factors and inflammation in pre-hypertensive men: a double-blind randomized placebo-controlled crossover study.

High intake of fruits and vegetables is associated with reduced cardiovascular risk. A number of fruits and vegetables are rich in anthocyanins, which constitute a subgroup of the flavonoids. Anthocyanins have demonstrated anti-inflammatory and anti-oxidative properties, and anthocyanin-rich interventions have indicated beneficial effects on blood pressure and other cardiovascular risk factors. We assessed whether a purified anthocyanin supplement improves cardiovascular metabolic risk factors and markers of inflammation and oxidative stress in prehypertensive participants, and whether plasma polyphenols are increased 1–3 h following intake. In all, 31 men between 35–51 years with screening blood pressure >140/90 mm Hg without anti-hypertensive or lipid-lowering medication, were randomized in a double-blinded crossover study to placebo versus 640 mg anthocyanins daily. Treatment durations were 4 weeks with a 4-week washout. High-density lipoprotein (HDL)-cholesterol and blood glucose were significantly higher after anthocyanin versus placebo treatment (P=0.043 and P=0.024, respectively). No effects were observed on inflammation or oxidative stress in vivo, except for von Willebrand factor, which was higher in the anthocyanin period (P=0.007). Several plasma polyphenols increased significantly 1–3 h following anthocyanin intake. The present study strengthens the evidence that anthocyanins may increase HDL-cholesterol levels, and this is demonstrated for the first time in prehypertensive and non-dyslipidemic men. However, no other beneficial effects in the short term were found on pathophysiological markers of cardiovascular disease.