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BackgroundUsing contemporary data from NORIC (Norwegian Registry of Invasive Cardiology) we investigated the predictive value of patient age and time from ECG diagnosis to sheath insertion (ECG‐2‐sheath) in primary percutaneous coronary intervention for ST‐segment–elevation myocardial infarction (STEMI).Methods and ResultsData from 11 226 patients collected from all centers offering 24/7/365 primary percutaneous coronary intervention service were explored. For patients aged Pvalue 80 years and mortality at 30 days, mortality was 10.5% and 17.7% for Restricted mean survival gains during median 938 days of follow‐up in patients with ECG‐2‐sheath time ConclusionsTime from ECG‐diagnosis to sheath insertion is strongly correlated with mortality. This applies especially to octogenarians who derive the most in terms of absolute mortality reduction.RegistrationURL:https://helsedata.no/en/forvaltere/norwegian‐institute‐of‐public‐health/norwegian‐registry‐of‐invasive‐cardiology/.

Introduction If reperfusion can be performed within 120 minutes, pPCI is the ESC guideline recommended treatment in patients with ST-elevation myocardial infarction (STEMI). Aims Historically, prognosis is dependent on time from diagnosis to reperfusion in patients with STEMI. We sought to investigate this in a contemporary patient population by assessing mortality as function of time from ECG diagnosis to sheath insertion in the Norwegian registry for invasive cardiology (NORIC). Methods NORIC, which is a part of the Norwegian Cardiovascular Disease Registry, is a national, mandatory and non-consensual person-identifiable health registry. Data from NORIC were linked with the National Population Register. Data were registered from 1st of January 2013 to 31st of June 2019. Results During this period complete data were available for n=5754 patients with 526 events. ECG diagnosis to sheath insertion was a predictor of mortality with the 4th (>106 min) vs 1st quartile ( Nationally 62% percent of the patients received pPCI within the ESC recommended 90 minutes from ECG-diagnosis with large geographical variation (range 38–89%). Nationally 80% received pPCI within 115 minutes (range 75–202 minutes). Conclusion In a contemporary STEMI population, time from ECG diagnosis to sheath insertion is a strong predictor for mortality in patients admitted for pPCI for STEMI. However, the data also demonstrate large variations between different geographical health regions in Norway that should be addressed. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Haukeland University Hospital

Introduction Limitations of the current reports on prognosis in ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), are that they are based on selected samples from hospitals voluntary registries, trials and surveys and thereby lack full population coverage. In contrast to most developed countries, Sweden and the UK were for a long term, the only two countries worldwide that had continuous national clinical registries for acute coronary syndrome with mandated participation for all hospitals. This is now also the case in Norway. Of all STEMIs admitted to hospital in Norway, 77% is treated with PCI (2016). Since 2013 invasive coronary procedures is registered in The Norwegian registry for invasive cardiology (NORIC). Purpose The purpose of the current report from NORIC was to assess the mortality rates in patients treated with PCI for STEMI in Norway. Moreover we sought to assess the relationship between mortality and age at admission in this population. Methods NORIC, which is a part of the Norwegian Cardiovascular Disease Registry (NCDR), is a national person-identifiable health registry that does not require consent from the registered individual. Data were registered from 1st of January 2013 to 13th of June 2018. Results During this period 10524 patients were registered with a STEMI. The incidence is calculated for the years of 2015–2017 when the registry had full national coverage. The incidence of STEMI treated with PCI in Norway was (53 in 2015, 50 in 2016 and 52 in 2017 per 100 000). For patients younger than 80 years at admission, the mortality rates were 4.9%, 6.8% and 8.0% at 30 days, 365 days and 730 days respectively. For patients older than 80 years at admission the mortality rates were 8.3%, 15.6% and 19.0% at 30 days, 365 days and 730 days respectively. The mortality rates stratified by age are illustrated in figure 1. Survival stratified by age Conclusions Mortality in STEMI patients offered primary PCI in Norway is equal or even lower than the mortality reported from well-established national registries from UK and Sweden. This indicates a well functioning treatment strategy despite challenging geography. Age is an important determinant of mortality.

Background: The optimal management of elderly patients with non-ST-segment elevation myocardial infarction (NSTEMI) is still discussed. We aimed to study short- and long-term survival in NSTEMI patients ≥75 years managed with an invasive or a conservative strategy. Methods: NSTEMI patients admitted to Oslo University Hospital Ulleval during 2005–2011 were included consecutively in a prospective registry. Vital status until December 31, 2013, was obtained from the Norwegian Cause of Death Registry. Patients ≥75 years were identified, and 30-day and 7-year survival were analyzed. Logistic- and Cox regression was used to estimate OR and hazard ratio (HR) for death in the invasive versus conservative group, adjusting for registered confounders. Results: There were 2,064 NSTEMI patients ≥75 years (48.2% women); 1,200 (58.1%) were treated with an invasive strategy, and were younger, more likely to be male and previously revascularized compared to 864 (41.9%) patients treated conservatively (p < 0.0001 for all). Survival at 30-day was 94.9% in the invasive and 76.6% in the conservative group. For 30-day survivors, 7-year survival was 47.4% (95% CI 42.9–51.8) and 11.6% (95% CI 8.3–15.6), respectively. After multivariate adjustment, an invasive strategy was associated with lower long-term risk (adjusted HR [aHR] 0.49 [95% CI 0.41–0.59]). Actual revascularization was associated with lower risk of long-term mortality compared to angiography only (aHRPCI 0.73 [95% CI 0.59–0.90], aHRCABG 0.43 [95% CI 0.28–0.65]). Conclusion: In this real-life cohort of NSTEMI patients ≥75 years, 30-day survival was 95%, and 7-year survival was 47% with an invasive strategy. Revascularized patients had a superior long-term prognosis. With a conservative strategy, short- and long-term survival was lower, probably due to selection bias and unmeasured confounding.

Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life.We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life.At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups.In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

We aimed to study in-hospital mortality and long-term survival in elderly compared to younger patients with ST-segment elevation myocardial infarction (STEMI) in the era of primary angioplasty.This was a prospective cohort study. All consecutive STEMI-patients admitted to our hospital between September 2005-December 2011 were included in a local registry. Predefined variables were registered during hospital admission. Vital status was obtained from the Norwegian Cause of Death Registry with censoring date 31 December 2011. Adjusted effects of age ⩾80 years on in-hospital- and long-term mortality were determined using propensity score analysis. Of 4525 registered STEMI patients, 600 (13%) were octogenarians or older. In-hospital mortality was 17% in patients ⩾80 years and 4% in patients80 years. In invasively treated patients (83% of patients ⩾80 years; 98% of patients80 years), in-hospital mortality was 13% and 3.4%, respectively. Median follow-up time was 2.5 years. Three-year cumulative survival was 52% in patients ⩾80 years vs 89% in patients80 years. In invasively treated patients ⩾80 years, three-year survival was 58%. The adjusted odds ratio of in-hospital mortality was 2.61 (1.94-3.52) and adjusted incidence rate ratio of long-term mortality was 4.07 (3.43-4.84) in very elderly compared to younger patients.Short-term prognosis was acceptable in very elderly STEMI patients, especially in the invasively treated subgroup. However, only 52% of STEMI patients ⩾80 years were alive after three years of follow-up. Very elderly patients had 2.6 times higher risk of in-hospital mortality and 4.1 times the risk of not surviving during long-term follow-up compared to patients80 years, after adjustment for confounding factors and selection bias.

Background Renal denervation (RDN) has been introduced as a potential new treatment for patients with treatment-resistant hypertension, defined as a blood pressure above 140/90 mm Hg despite treatment with at least three antihypertensive drugs. We present an overview of this type of treatment, describe the method and discuss its possible future uses. Method The review is based on a discretionary selection of relevant articles from our archive, our own experience and a literature search in PubMed. Results The use of RDN for treatment-resistant hypertension is based on a single randomised study with a total of 104 patients, in which the intervention group experienced a fall in blood pressure of 32/12 mm Hg, while blood pressure in the control group remained unchanged. More than 16,000 patients, particularly in Germany, have been treated on this basis. In the USA, data from a larger randomised study (n = 530) that includes sham surgery are awaited before any decision is made on whether to approve the method for use. Interpretation Before RDN can become recommended treatment in Norway, more evidence is required that the method lowers blood pressure, and that this reduces morbidity and mortality.

Our objective was to evaluate the ability of CMR to visualize myocardial injuries over the course of myocarditis. We studied 42 patients (39 males, 3 females; age 37 ± 14 years) with myocarditis during the acute phase and after 12 ± 9 months. CMR included function analyses, T2-weighted imaging (T2 ratio), T1-weighted imaging before and after i.v. gadolinium injection (global relative enhancement; gRE), and late gadolinium enhancement (LGE). In the acute phase, the T2 ratio was elevated in 57%, gRE in 31%, and LGE was present in 64% of the patients. In 32 patients (76%) were any two (or more) out of three sequences abnormal. At follow-up, there was an increase in ejection fraction (57.4 ± 11.9% vs. 61.4 ± 7.6; P

A variety of conditions other than acute myocardial infarction may cause ST-elevation. Our objective was to evaluate the impact of cardiac magnetic resonance (CMR) on differential diagnosis from a prospective series of patients with suspected ST-elevation myocardial infarction (STEMI) and completely normal coronary arteries. Among 1,145 patients with suspected STEMI, 49 patients had completely normal coronary arteries and entered a prospective registry. CMR was done within 24 h, if possible, and included function analyses, T2-weighted imaging (T2 ratio), T1-weighted imaging before and after gadolineum administration (global relative enhancement; gRE), and late gadolineum enhancement (LGE). All patients were asked for a follow-up CMR after approximately 3 months. The incidence of patients with suspected STEMI and normal coronary arteries was 4.3% and mean age was 45 ± 14 years (STEMI group 64 ± 13 years; P

Left ventricular (LV) hypertrophy is related to blood pressure level and neurohormonal factors. The authors previously demonstrated that arterial norepinephrine levels predict LV mass in middle-aged men who developed hypertension through 20 years. The aim of this 20-year prospective study was to investigate arterial vasopressin, aldosterone, and renin as long-term predictors of LV mass. Normotensives (n=17), subjects who developed hypertension (n=17), and sustained hypertensives (n=22) were compared at baseline (42 years) and at follow-up (62 years). There were no significant differences in baseline vasopressin, aldosterone, or renin levels. The group with sustained hypertension had more LV hypertrophy (P=.025) at follow-up. Among new hypertensives, multiple regression analysis demonstrated that baseline arterial vasopressin (beta-0.53; P=.041) and aldosterone (beta-0.56;P=.032) independently explained LV mass index (R(2)=0.85; P=.035). In conclusion, baseline arterial vasopressin and aldosterone, but not renin, appear to predict LV mass in middle-aged men who developed hypertension over a 20-year period.

Background— We aimed to investigate coronary angiographic findings in unselected out-of-hospital cardiac arrest patients referred to immediate coronary angiography (ICA) irrespective of their first postresuscitation ECG and to determine whether this ECG is useful to select patients with no need of ICA. Methods and Results— All resuscitated patients admitted after out-of-hospital cardiac arrest without a clear noncardiac cause underwent ICA. Patients were retrospectively grouped according to the postresuscitation ECG blinded for ICA results: (1) ST elevation or presumably new left bundle branch block, (2) other ECG signs indicating myocardial ischemia, and (3) no ECG signs indicating myocardial ischemia. All coronary angiograms were reevaluated blinded for postresuscitation ECGs. Two hundred and ten patients were included with mean age 62±12 years. Six-months survival with good neurological outcome was 54%. Reduced Thrombolysis in Myocardial Infarction flow (0–2) was found in 55%, 34%, and 18% and a ≥90% coronary stenosis was present in 25%, 27%, and 19% of patients in group 1, 2, and 3, respectively. An acute coronary occlusion was found in 11% of patients in group 3. ST elevation/left bundle branch block identified patients with reduced Thrombolysis in Myocardial Infarction (0–2) flow with 70% sensitivity and 62% specificity. Among patients with initial nonshockable rhythms (24%), 32% had significantly reduced Thrombolysis in Myocardial Infarction flow. Conclusions— Initial ECG findings are not reliable in detecting patients with an indication for ICA after experiencing a cardiac arrest. Even in the absence of ECG changes indicating myocardial ischemia, an acute culprit lesion may be present and patients may benefit from emergent revascularization. Clinical Trial Registration—URL: http://www.clinicaltrials.gov . Unique identifier: NCT01239420.

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.

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.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.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.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.

In the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study, there was a 25% risk reduction for stroke with angiotensin receptor blocker-based therapy (losartan) as compared with beta-blocker-based therapy (atenolol) despite comparable blood pressure reductions. This substudy examines treatment effects on the amount and density of atherosclerotic lesions in the common carotid arteries and the carotid bulb in 81 patients during 3 years of treatment. There were no statistically significant changes in the amount of carotid plaque in patients treated with losartan compared with an atenolol-based treatment program. A statistically nonsignificant increase in plaque density and index (average of plaque amount and density) was seen in the atenolol group compared with those treated with losartan. The small number of patients evaluated may have limited the power to detect a difference in outcome. The difference in carotid plaque index increase between the treatment groups during 3 years of treatment could not be statistically linked to specific treatments in the present substudy.

The aim of this study was to investigate the effects of losartan- vs atenolol-based antihypertensive treatment on circulating collagen markers beyond the initial blood pressure (BP) reduction.In 204 patients with hypertension and left ventricular (LV) hypertrophy we measured serum concentration of carboxy-terminal telopeptide of type I procollagen (ICTP), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), amino-terminal propeptide of type I procollagen (PINP) and LV mass by echocardiography at baseline and annually during 4 years of losartan- or atenolol-based antihypertensive treatment; 185 patients completed the study.Beyond the first year of treatment systolic and diastolic BP, LV mass index (LVMI) as well as collagen markers did not change significantly and were equal in the two treatment groups. Changes in PICP during first year of treatment were related to subsequent changes in LV mass index after 2 and 3 years of treatment (r=0.28 and r=0.29, both p0.05) in patients randomized to losartan, but not atenolol.Long-term losartan- vs atenolol-based antihypertensive treatment did not influence collagen markers differently, making a BP-independent effect of losartan on collagen markers unlikely. However, initial reduction in circulating PICP may predict later regression of LV hypertrophy during losartan-based antihypertensive treatment.

The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with hypertension taking aspirin : the Losartan Intervention for Endpoint Reduction in hypertension (LIFE) study.

We studied plasma adrenaline (A) in relation to physical fitness, metabolic cardiovascular risk factors and cardiovascular responses. Men (age 21-24 years) with high and normal (both n=19) screening blood pressure (BP) were studied cross-sectionally. We measured peak oxygen uptake (VO2peak) (treadmill exercise), and plasma catecholamines, heart rate (HR), finger systolic (SBP) and diastolic (DBP) BP, and insulin-adjusted glucose disposal rate (GDR/I) during a hyperinsulinaemic glucose clamp (rest) and mental arithmetic stress test (MST). By multiple regression, A at rest (Arest) (beta=0.37, p0.05) and during MST (Amst) (beta=0.40, p0.01) were associated with high screening BP. In the respective models, Arest was negatively related to body mass index (BMI) (beta=-0.56, p0.001) and Amst positively to VO2peak (beta=0.54, p0.001). BP and HR responses correlated positively with VO2peak, but were determined by Amst in multiple regression models. Independently of BMI and VO2peak, serum high-density lipoprotein cholesterol was positively related to A levels, whereas GDR/I was independently related only to VO2peak. Increased adrenaline secretion may be related to high BP, but may at the same time be associated with a beneficial metabolic profile.

OBJECTIVES We hypothesized that insulin sensitivity and vagal cardiac control are independently related in young men after adjustment for fitness and other confounding variables. DESIGN Male volunteers aged 21-24 years with high (borderline hypertensive; n = 20) and low-normal (normotensive; n = 21) screening blood pressure (BP) were studied cross-sectionally. METHODS Mean R-R interval (RR) and heart rate variability (HRV) were computed from 30-min ECGs, and baroreflex sensitivity (BRS) and latency (phase shift) from 15-min beat-to-beat finger blood pressure (BP) and heart rate recordings. Insulin-adjusted glucose disposal rate (GDR/I) was measured with a 90-min hyperinsulinaemic glucose clamp and fitness by peak oxygen uptake (VO2peak) during a treadmill test. RESULTS HRV, baroreflex function, GDR/I, and VO2peak did not differ between the groups. GDR/I correlated positively with time and frequency domain HRV, including high-frequency power (HF) (r = 0.40, P = 0.01) and root-mean squared successive differences (RMSSD) (r = 0.43, P = 0.005), but not BRS or phase shift. GDR/I correlated with VO2peak (r = 0.70, P < 0.0001) and was explained (R = 0.56) by VO2peak (beta = 0.57, P < 0.0001) and RR (beta = 0.29, P = 0.03), independently of HRV and measures of obesity. Conversely, RR (beta = 0.55, P = 0.0004) and HRV, including HF (beta = 0.44, P = 0.006) and RMSSD (beta = 0.46, P = 0.004) were explained by GDR/I, independently of VO2peak. CONCLUSIONS Insulin sensitivity and autonomic cardiac control are related independently of physical fitness in young men.

BACKGROUND N-terminal pro-brain natriuretic peptide (Nt-proBNP) and N-terminal pro-atrial natriuretic peptide (Nt-proANP) are strong cardiovascular risk markers in patients with chronic heart failure, as well as in the general population. We investigated whether high Nt-proBNP or Nt-proANP could also predict the composite endpoint (CEP) of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction in patients with hypertension and left ventricular (LV) hypertrophy. METHODS After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 183 hypertensive participants in the LIFE echo substudy with electrocardiographic LV hypertrophy. Nt-proBNP and Nt-proANP were measured by immunoassay at baseline. The patients were followed for 60 +/- 5 months. RESULTS Using Cox regression analysis, the 25 CEP were predicted by ln(Nt-proBNP) (hazard ratio 1.61 per 2.73-fold increase, P < 0.01) as well as ln(Nt-proANP) (hazard ratio 2.93, P < 0.05). Nt-proBNP above the median value of 21.8 pmol/ml was associated with higher incidence of CEP (19.6 versus 7.7%, P < 0.05). Nt-proBNP above the median value was associated with higher incidence of CEP in the 123 patients without history of diabetes or cardiovascular disease (14.8 versus 4.3%, P < 0.05), but the association was insignificant in the 60 patients with a history of diabetes or cardiovascular disease (26.3 versus 18.2%, NS). Nt-proANP showed the same tendency. CONCLUSION Nt-proBNP, more than Nt-proANP, strongly predicts cardiovascular events in patients with hypertension and LV hypertrophy, especially in patients without diabetes or clinically overt cardiovascular disease.

Background There may be a link among stress, adrenal medullary activation, and the development of hypertension. Obesity is characterized by sympathetic activation and predisposes to hypertension, but may be associated with low or normal adrenal medullary activity. We hypothesized that plasma epinephrine (E) levels and adrenal medullary responsiveness to mental stress are lower in overweight than in lean borderline hypertensive subjects. Methods We compared groups of lean ( n = 62) and overweight ( n = 29) borderline hypertensive young men as well as lean ( n = 36) and overweight ( n = 7) normotensive young men from the same population. Plasma catecholamines and heart rate (HR) were measured at rest during a hyperinsulinemic glucose clamp and during mental arithmetic–induced stress. Results Plasma norepinephrine (NE) and E, HR, and responses to stress were increased in borderline hypertensive subjects. Our results showed that NE was increased only in lean borderline hypertensive subjects at rest, but in overweight subjects as well during stress, with ΔNE being similar in lean and overweight subjects. We found that E was higher in lean than in overweight borderline hypertensive subjects at rest and during stress (both P P P P P = .02). Conclusions Sympathetic neural activity and responsiveness are increased in borderline hypertensive young men, but measures of overweight are independently related to lower plasma E and HR responses. We suggest that adrenal medullary activation in borderline hypertension mainly characterizes lean subjects.

The cardiovascular metabolic syndrome is characterized by the presence of several cardiovascular risk factors, including blood pressure (BP) elevation. We aimed to study the relation between mental stress, plasma catecholamines, BP and BP responses to mental stress in healthy young Caucasian men selected from different levels of screening BP. We included 98 men with high and 22 men with normal screening BP. They were examined at baseline in the laboratory, during a hyperinsulinemic, isoglycemic glucose clamp and during mental stress. At baseline in the laboratory, the men with high screening BP were characterized by elevated BP (p0.005) and plasma catecholamines (p0.05), but unaltered serum lipid levels compared to men with normal screening BP. After 2 h rest the differences almost disappeared, but could be reproduced during a mental arithmetic stress test. The men with elevated screening BP had significantly higher fasting glucose (p = 0.01) and lower insulin sensitivity (p0.005). In a multiple regression model, norepinephrine during mental stress (R2 = 0.10, p0.05) was the main variable to retrospectively explain allocation to the normal or high screening BP group. In conclusion, young healthy men with elevated screening BP are characterized by increased sympathetic activity and insulin resistance. Norepinephrine during mental stress is the main variable to explain allocation to the normal or elevated screening BP group. We have shown that one single screening BP measurement predicts insulin resistance and elevated fasting glucose in this cohort.

We assessed plasma noradrenaline (NA) and adrenaline (A) at rest during a hyperinsulinaemic glucose clamp and responses to a mental arithmetic stress test (MST) in relation to blood pressure (BP) responses (Finapres) and distress in 20 men with high (or =140/90 mmHg) and 21 men with normal (or =115/75 mmHg) screening BP, 21-24 years of age. Perceived stress, effort and overall discomfort were scored 1-10. Catecholamines and BP increased in both groups, change in diastolic BP (DeltaDBP; 9.9 vs. 3.8 mmHg, p0.05) and DeltaDBP carryover (recovery period minus baseline) (7.2 vs. 2.2 mmHg, p0.01) being greater in men with high screening BP. Independently of BP status, change in systolic BP (DeltaSBP) and DeltaSBP carryover were related to A (both p0.001), and DeltaDBP and DeltaDBP carryover to DeltaNA (both p0.001). The subjective score sum correlated with maximal NA (rs = 0.40) and A (rs = 0.37) (both p0.05). Maximal NA was independently related to stress (p0.05) and the subjective score sum (p0.01). DeltaA% was greater in the high- (scoreor =6) than in the low-stress category, independently of BP status (p0.05). High screening BP is associated with impaired BP recovery after mental stress. Plasma catecholamine responses are related to BP responses and carryover effects, and reflect perceived stress in young men.

Serum uric acid (SUA) but also hemorheological parameters such as hematocrit (Hct) and whole blood viscosity (WBV) are markers of cardiovascular risk. Increased blood cell volume is one of the known causes of hyperuricemia. We therefore aimed to investigate the relationship between SUA and hemorheology in untreated borderline hypertensive young men (n = 67) and in subjects with established hypertension and left ventricular hypertrophy (n = 40) examined when they had been without treatment for 2 weeks. We found positive correlations between SUA and Hct (r = 0.46, p < 0.0001), hemoglobin (Hgb) (r = 0.40, p = 0.001), mean blood pressure (BP) (r = 0.39, p = 0.001) and body weight (r = 0.26, p = 0.036) in the borderline hypertensive young men. No relation between SUA and glucose disposal rate (GDR) assessed with hyperinsulinemic isoglycemic glucose clamp appeared (r = -0.06, p = 0.633). Multiple regression analysis showed that 33% of the variation in SUA could be explained by BP and Hct. We also found positive correlations between SUA and Hgb (r = 0.40, p = 0.011) and body weight (r = 0.42, p = 0.006) and an inverse trend with GDR (r = -0.27, p = 0.087) in the subjects with established hypertension. Multiple regression showed that 32% of the variation in SUA was explained by Hgb and body weight. These data suggest that hemorheology may be involved in the uric acid metabolism in borderline as well as in established hypertensives. Hemorheology may possibly be a link between SUA and cardiovascular risk. There was no relation between SUA and insulin resistance in these hypertensive groups.

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 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

Renal denervation (RDN) has been introduced as a potential new treatment for patients with treatment-resistant hypertension, defined as a blood pressure above 140/90 mm Hg despite treatment with at least three antihypertensive drugs. We present an overview of this type of treatment, describe the method and discuss its possible future uses.The review is based on a discretionary selection of relevant articles from our archive, our own experience and a literature search in PubMed.The use of RDN for treatment-resistant hypertension is based on a single randomised study with a total of 104 patients, in which the intervention group experienced a fall in blood pressure of 32/12 mm Hg, while blood pressure in the control group remained unchanged. More than 16,000 patients, particularly in Germany, have been treated on this basis. In the USA, data from a larger randomised study (n = 530) that includes sham surgery are awaited before any decision is made on whether to approve the method for use.Before RDN can become recommended treatment in Norway, more evidence is required that the method lowers blood pressure, and that this reduces morbidity and mortality.

We aimed to study the glycemic response to epinephrine during hyperinsulinemia and infused epinephrine (0.03 microg/kg/min) for 30 min after 90 min of hyperinsulinemic glucose clamp in 14 borderline hypertensive young men. Plasma epinephrine was increased from 0.34 +/- 0.08 to 2.33 +/- 0.33 nmol/L while insulin and glucose infusions were kept constant with consequent changes in blood glucose. Initially (90 to 95 min), there was a decrease in blood glucose (P = .016) that correlated negatively with glucose disposal rate corrected for insulin (r = -0.55, P = .040) and positively with fasting insulin (r = 0.55). Thereafter, there was an increase in blood glucose (95 to 120 min) (P < .001) that persisted during the recovery period (120 to 140 min). The glucose increase (90 to 140 min) correlated positively with fasting insulin (r = 0.55), systolic blood pressure (r = 0.57), delta epinephrine 90 to 120 min (r = 0.59), and baseline epinephrine (r = 0.57). Blood glucose remained unchanged (P = .207) in a saline control group (n = 6) with a significant group X treatment effect versus epinephrine (P = .003). Thus, epinephrine caused a biphasic response in blood glucose during hyperinsulinemia. The initial dip in glucose was more pronounced with higher insulin sensitivity, corresponding to previous observations during mental stress test. The following increment in blood glucose was positively related to insulin, systolic blood pressure, and epinephrine levels. These data suggest that insulin may modify the glycemic response to epinephrine in a potentially favorable direction and indicate some lag time before epinephrine gains effect. Subjects who are insulin sensitive and have low blood pressure and resting epinephrine levels seem to be less prone to hyperglycemia induced by epinephrine.

Chronic occlusion of the left coronary artery is an infrequent finding in patients undergoing coronary angiography. These patients usually present symptoms of angina or heart failure. We describe a patient who was training regularly without cardiac symptoms until ventricular fibrillation suddenly occurred during a long-distance run. A chronic left main stem occlusion with well-developed right-to-left coronary collaterals was demonstrated by angiography. Up to this event, the collateral flow had been sufficient to allow physical exercise at a high performance level without symptoms. The patient later underwent coronary bypass surgery and recovered completely.

In a recent study, we could not find evidence to support the hypothesis that insulin activates the sympathetic nervous system (SNS) during a hyperinsulinemic glucose clamp procedure. Mental stress tests (MST), however, may be used to detect differences in blood pressure and SNS activity that are not present during baseline or resting conditions. In this study, we aimed to investigate the effects of hyperinsulinemia during glucose clamp on blood pressure and sympathetic responses to mental stress. Borderline hypertensive but otherwise healthy 21-year-old men (n = 18) underwent 5 min of mental arithmetic stress testing (MST-1) before and at the end of 120 min of isoglycemic hyperinsulinemic glucose clamp (MST-2) with infusion rates of glucose and insulin kept constant. Insulin concentration increased from 119 +/- 10 pmol/L to 752 +/- 65 pmol/L. We observed highly significant increases in blood pressure and heart rate in response to MST, but neither insulin nor saline solution infusions affected these responses. During MST-1, norepinephrine increased by 461 +/-165 pmol/L (mean +/- SEM) and epinephrine by 218 +/- 76 pmol/L. During MST-2 the changes were 372 +/- 112 pmol/L and 187 +/- 60 pmol/L, respectively. The norepinephrine (P = .8) and epinephrine (P = .7) responses were unchanged by insulin. Thus, there were similar increases in blood pressure, heart rate, and plasma catecholamine concentrations in arterialized venous blood in response to MST despite the infusion of insulin. A possible time effect was excluded by including a saline solution control group (n = 7) that showed almost identical results. Our results suggest that acute hyperinsulinemia during isoglycemic glucose clamp does not interfere with cardiovascular or sympathetic responses to mental stress.

We have seen relationships between whole blood viscosity (WBV) and components of the metabolic cardiovascular syndrome in borderline hypertensive young men and suggested that sympathetic nervous system (SNS) activity may be a mediator. In the present study we aimed to test this hypothesis in established hypertension and to investigate the relationship between WBV and cardiac dimensions. Unmedicated patients (n = 42) with stage II-III hypertension and electrocardiographic left ventricular hypertrophy (LVH) underwent hyperinsulinemic isoglycemic glucose clamp to assess glucose disposal rate (GDR) and echocardiographic studies. WBV, plasma catecholamines and insulin were measured in arterialized venous blood. WBV at high shear rate correlated with baseline plasma adrenaline (r = 0.33, p = 0.04) and fasting insulin (r = 0.34, p = 0.04) while there was a negative trend for GDR (r = -0.21, p = 0.2). WBV at low shear rate correlated with plasma adrenaline (r = 0.49, p = 0.002) and resting heart rate (r = 0.36, p = 0.02). WBV was higher in smokers than in non-smokers (p = 0.02) and in males than in females (p = 0.02). Fasting insulin independently explained 12% of the variation in WBV at high shear, while baseline adrenaline independently explained 17% of the variation in WBV at low shear. Systolic blood pressure explained 31% of the variation in LV mass index. Thus, we demonstrate positive relationships between blood viscosity versus plasma adrenaline and fasting insulin in hypertensive patients with LVH. We suggest that adrenergic activity may increase hematocrit and viscosity and hence reduce insulin sensitivity.

BACKGROUND Insulin resistance is associated with hypertension. The relative influences of hyperinsulinaemia and high blood pressure on vascular hypertrophy and carotid distensibility is unclear in patients with longstanding hypertension. METHODS In 88 unmedicated patients with stage II-III hypertension and left ventricular hypertrophy on electrocardiogram we measured blood pressure, minimal forearm vascular resistance (MFVR) using plethysmography, intima-media thickness (IMT) and the wall distensibility of the common carotid arteries using ultrasound, and insulin sensitivity using a 2-h isoglycaemic hyperinsulinaemic clamp. RESULTS IMT was positively correlated to systolic blood pressure (r= 0.26, P < 0.05), whole body glucose uptake index (M/IG; r= 0.22, P< 0.05), age (r= 0.24, P< 0.05) and negatively correlated to body mass index (r= -0.24, P < 0.05); IMT did not correlate to fasting serum insulin (r= -0.14, NS). In men (n = 64) MFVR was positively correlated to systolic blood pressure (r = 0.30, P < 0.05), but was unrelated to M/G and serum insulin. The distensibility of the common carotid arteries was negatively correlated to systolic blood pressure (r = -0.40, P< 0.001) and in untreated patients (n = 22) positively correlated to M/IG (r = 0.47, P < 0.05). CONCLUSIONS High systolic blood pressure was related to vascular hypertrophy, whereas hyperinsulinaemia and insulin resistance were not, suggesting that longstanding high blood pressure is a far more important determinant for structural vascular changes than insulin resistance at this stage of the hypertensive disease. However, hyperinsulinaemia and insulin resistance were associated with low distensibility of the common carotid arteries in the subgroup of never treated hypertensive patients.

In a previous study we found that elevated blood viscosity was linked to the insulin resistance syndrome, and we proposed that high blood viscosity may increase insulin resistance. That study was based on calculated viscosity.To determine whether directly measured whole-blood viscosity was related to the insulin-resistance syndrome in the same way as calculated viscosity had been found to be.Healthy young men were examined with the hyperinsulinemic isoglycemic glucose clamp technique, and we related insulin sensitivity (glucose disposal rate) to other metabolic parameters and to blood viscosity. We established a technique for direct measurement of whole-blood viscosity.There were statistically significant negative correlations between glucose disposal rate and whole-blood viscosity at low and high shear rates (r = -0.41, P = 0.007 for both, n = 42). Whole-blood viscosity was correlated positively (n = 15) to serum triglyceride (r = 0.54, P = 0.04) and total cholesterol (r = 0.52, P = 0.05), and negatively with high-density lipoprotein cholesterol (r = -0.53, P = 0.04) concentrations. Insulin sensitivity index was correlated positively to high-density lipoprotein cholesterol (r = 0.54, P = 0.04) and negatively to serum triglyceride (r = -0.69, P = 0.005) and to total cholesterol (r = -0.81, P = 0.0003) concentrations.The present results demonstrate for the first time that there is a negative relationship between directly measured whole-blood viscosity and insulin sensitivity as a part of the insulin-resistance syndrome. Whole-blood viscosity contributes to the total peripheral resistance, and these results support the hypothesis that insulin resistance has a hemodynamic basis.

Whole blood viscosity contributes to the total peripheral resistance and has been suggested to be a risk factor for cardiovascular disease. Whole blood viscosity was measured using a direct technique in 105 healthy blood donors and in addition to establishing our reference values, the relationship to blood pressure and other cardiovascular risk factors was assessed. Whole blood viscosity correlated with systolic blood pressure (r = 0.29, p = 0.003), cholesterol (r = 0.21, p = 0.034), cholesterol/HDL cholesterol ratio (r = 0.33, p = 0.01), triglycerides (r = 0.37, p0.0005), body mass index (r = 0.29, p = 0.003) and waist-hip ratio (r = 0.30, p = 0.002). Subjects with systolic blood pressure130 mmHg (n = 16) had higher whole blood viscosity (p = 0.017) than those with lower blood pressure. Whole blood viscosity was significantly lower in women (n = 52) than in men at all shear rates (0.045p0.001). These results suggest that even in a population of healthy normotensive blood donors of a wide age range and either gender, there are positive correlations between directly assessed whole blood viscosity and a number of the components of the metabolic cardiovascular syndrome including systolic blood pressure, weight and blood lipids.

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.

Takotsubo cardiomyopathy (TTC) is a diagnostic entity that is increasingly being recognized. Data from cardiac magnetic resonance (CMR) imaging and its impact on differential diagnosis are limited.After 26 months, coronary angiography revealed normal coronary arteries and left ventriculography and/or echocardiography left ventricular dysfunction with apical ballooning in 20 patients with acute coronary syndrome (ACS). Four patients were excluded from CMR and in three patients an alternative diagnosis was revealed. Thirteen patients (all female; 60 ± 8 years) with TTC underwent a multisequential CMR, in which all showed myocardial oedema with an elevated T2 ratio in the apical region (2.4 ± 0.4; p0.001 vs. healthy controls), and five patients an elevated global relative enhancement (gRE; 3.7 ± 1.4; p0.05 vs. healthy controls). No late gadolinium enhancement (LGE) was detected on CMR. Follow-up after 132 ± 33 days showed a normalized left ventricular ejection fraction, myocardial mass, T2 ratio, and gRE in all patients.TTC is a small but definite group among patients with ACS and normal coronary arteries. CMR allows differentiating TTC from other causes such as myocarditis and cardiomyopathies, as well as to identify the transient increase of myocardial mass and resolution of myocardial oedema as the systolic dysfunction improves. Therefore, CMR might add valuable information for the differential diagnoses and therapeutic decision-making in patients with suspected TTC.

Fossum E, Gleim GW, Kjeldsen SE, Kizer JR, Julius S, Devereux RB, Brady WE, Hille DA, Lyle PA, Dahlof B (University of Oslo, Oslo, Norway, Merck Research Laboratories, West Point, PA; University of Michigan, Ann Arbor, MI, Comell University, New York, NY, USA; and University Hospital/Ostra, Goteborg, Sweden). The effect of baseline physical activity on cardiovascular outcomes and new-onset diabetes in patients treated for hypertension and left ventricular hypertrophy: the LIFE study. J Intern Med 2007; 262: 439-448. Objectives. Physical activity (PA) is a preventive strategy for cardiovascular disease and for managing cardiovascular risk factors. There is little information on the effectiveness of PA for the prevention of cardiovascular outcomes once cardiovascular disease is present. Thus, we studied the relationship between PA at baseline and cardiovascular events in a high-risk population. Design. A prespecified analyses of observational data in a prospective, randomized hypertension study. Setting. Losartan Intervention For Endpoint reduction in hypertension (LIFE) study Subjects. Hypertension and left ventricular hypertrophy (LVH) (n = 9193). Interventions. Losartan versus atenolol. Main outcome measures. Reported level of PA: never exercise, exercise ≤30 min twice per week, or exercise >30 min twice per week at baseline and after a mean of 4.8 years of treatment with losartan- versus atenolol-based therapy. Risk reductions were calculated by level of PA for the primary composite end-point and its components cardiovascular death, stroke and myocardial infarction, and also all-cause mortality and new-onset diabetes. Results. A modest level of PA (>30 min twice per week) was associated with significant reductions in risk for the primary composite end-point [adjusted hazard ratio (aHR) 0.70, P 30 min twice per week) in patients with hypertension and LVH in the LIFE study was associated with significant reductions in risk for the primary composite end-point and its components of cardiovascular death, stroke, and myocardial infarction, all-cause mortality, and new-onset diabetes.

We have previously demonstrated that neurohormonal activity can predict left ventricular (LV) mass in men who developed hypertension over 20 years. The aim of the study was to investigate early markers of cardiac and hemorheological changes at baseline in these men, i.e., before a rise in blood pressure. Fifty-six middle-aged men were followed for 20 years; 22 were sustained hypertensives, 17 developed hypertension, and 17 were sustained normotensives. They were compared at baseline (42 years) and follow-up (62 years). We investigated Cornell voltage product and Sokolow-Lyon voltage, hematocrit (Hct), and echocardiographic LV parameters. There was no sign of LV hypertrophy by electrocardiography (ECG) at baseline. Baseline Hct discriminated between the groups ( P = .015) and correlated to diastolic blood pressure (DBP) at baseline ( r = 0.37, P = .006) and follow-up ( r = 0.31, P = .020). Regression analysis identified baseline Hct as an independent correlate of DBP in the cohort at baseline when they were untreated (β = .33, P = .013, R 2 = 0.25), and of borderline significance at follow-up (β = .26, P = .060, R 2 = 0.12) despite possible interference by antihypertensive drugs. Hct was elevated at baseline compatible with the hypothesis that pathogenic hemorheological processes could be activated at the outset and prior to cardiac changes in men who later develop hypertension.

We studied effects of mental stress on whole-blood viscosity (WBV) and blood pressure (BP), and relations between WBV and autonomic nervous system activity and insulin sensitivity. We measured WBV (rotational rheometer), plasma noradrenaline (NA), finger BP, heart rate variability (HRV) and baroreflex sensitivity (BRS; transfer technique) during hyperinsulinaemic glucose clamp and mental arithmetic stress test (MST) in 20 men with high ( > or =140/90 mmHg) and 21 men with normal (< or =115/75 mmHg) screening BP, and 10 women regardless of screening BP (all normotensive). WBV and NA increased during the MST, while HRV and BRS decreased. During the MST, WBV (all shear rates) and the response ((delta)WBV) (low shear) were higher in men with high compared to normal screening BP (p

BACKGROUND Secretion of natriuretic peptides is related to cardiac wall stress and influenced by the renin-angiotensin system. Therefore, we investigated the influence of blood pressure (BP) reduction with losartan versus atenolol on N-terminal pro-atrial natriuretic peptide (Nt-proANP) and N-terminal pro-brain natriuretic peptide (Nt-proBNP). METHODS In 183 patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy, enrolled in the LIFE Study, we measured BP and serum Nt-proANP and Nt-proBNP by immunoassay after 2 weeks of placebo treatment and after 1, 2, 4, 6, 12, 24, 36 and 48 months of randomized treatment with losartan- or atenolol-based antihypertensive regimens. RESULTS There was no significant difference in BP at any time point between the two treatment groups. In patients treated with losartan, median Nt-proANP decreased gradually throughout the study, reaching significance after 6 months of treatment (1125-1060 pmol/l, P < 0.001), and Nt-proBNP decreased within the first month (24.7-18.7 pmol/l, P < 0.01) and stayed reduced throughout the study. During losartan-based antihypertensive treatment, Nt-proANP and Nt-proBNP as a percentage of baseline values were correlated to reductions in systolic BP (r = 0.11, P < 0.01 and r = 0.10, P = 0.01) and diastolic BP (r = 0.17, P < 0.001 and r = 0.07, P = 0.09). In atenolol-treated patients, Nt-proANP (1100-1640 pmol/l, P < 0.001) and Nt-proBNP (20.0-37.7 pmol/l, P < 0.001) increased during the first month, and remained elevated throughout the study. During atenolol-based antihypertensive treatment, changes in Nt-proANP (r = -0.16, P < 0.001) and Nt-proBNP (r = -0.07, P = 0.08) were negatively related to change in heart rate. CONCLUSION Nt-proANP and Nt-proBNP were reduced in parallel with BP in losartan-treated patients whereas they increased in parallel with decreased heart rate in atenolol-treated patients.

We conducted a subgroup analysis in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study to determine whether aspirin interacted with the properties of losartan, an angiotensin-II receptor antagonist.Negative interactions between angiotensin-converting enzyme inhibitors and aspirin have been reported. There are no data reported from clinical trials about possible interactions between angiotensin-II receptor antagonists and aspirin.The LIFE study assigned 9,193 patients with hypertension and left ventricular hypertrophy (LVH) to losartan- or atenolol-based therapy for a mean of 4.7 years, with 1,970 (21.4%) taking aspirin at baseline. The primary composite end point (CEP) included cardiovascular death, stroke, and myocardial infarction (MI). The present cohort was stratified by aspirin use at baseline.Blood pressures were reduced similarly in the losartan with aspirin (n = 1,004) and atenolol with aspirin (n = 966) groups. The CEP was reduced by 32% (95% confidence interval 0.55 to 0.86, p = 0.001) with losartan with aspirin compared to atenolol with aspirin, adjusted for Framingham risk score and LVH. The test for treatment versus aspirin interaction, excluding other covariates, was significant for the CEP (p = 0.016) and MI (p = 0.037).There was a statistical interaction between treatment and aspirin in the LIFE study, with significantly greater reductions for the CEP and MI with losartan in patients using aspirin than in patients not using aspirin at baseline. Further studies are needed to clarify whether this represents a pharmacologic interaction or a selection by aspirin use of patients more likely to respond to losartan treatment.

Hypertension is a major risk factor for morbidity and mortality. Plasma catecholamines are linked to the pathogenesis of hypertension. Pharmacological intervention, including treatment with beta-blockers, reduces cardiovascular mortality and morbidity. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the angiotensin receptor blocker losartan significantly reduced cardiovascular end points compared to the beta-blocker atenolol. Thus, for the first time, one drug was shown to be superior to another in hypertension. The present substudy examined the effects of atenolol vs losartan treatment on plasma catecholamines at rest and during hyperinsulinaemia in a cohort of 86 LIFE patients. Plasma adrenaline increased significantly from placebo treatment at baseline to year 1 of treatment (P

(2003). Hypertension treatment and stroke prevention. Blood Pressure: Vol. 12, No. 5-6, pp. 264-268.

There may be a link among stress, adrenal medullary activation, and the development of hypertension. Obesity is characterized by sympathetic activation and predisposes to hypertension, but may be associated with low or normal adrenal medullary activity. We hypothesized that plasma epinephrine (E) levels and adrenal medullary responsiveness to mental stress are lower in overweight than in lean borderline hypertensive subjects.We compared groups of lean (n = 62) and overweight (n = 29) borderline hypertensive young men as well as lean (n = 36) and overweight (n = 7) normotensive young men from the same population. Plasma catecholamines and heart rate (HR) were measured at rest during a hyperinsulinemic glucose clamp and during mental arithmetic-induced stress.Plasma norepinephrine (NE) and E, HR, and responses to stress were increased in borderline hypertensive subjects. Our results showed that NE was increased only in lean borderline hypertensive subjects at rest, but in overweight subjects as well during stress, with DeltaNE being similar in lean and overweight subjects. We found that E was higher in lean than in overweight borderline hypertensive subjects at rest and during stress (both P.001), as were DeltaE and DeltaHR (both P.05). Independent of BP status, body mass index was negatively related to E during stress (P.01) and waist circumference negatively related to resting E (P.001) and DeltaHR (P =.02).Sympathetic neural activity and responsiveness are increased in borderline hypertensive young men, but measures of overweight are independently related to lower plasma E and HR responses. We suggest that adrenal medullary activation in borderline hypertension mainly characterizes lean subjects.

The effect of thrombolytic therapy in patients with myocardial infarction is well documented. In patients presenting with chest pain it may, however, be difficult to discriminate between myocardial infarction and aortic dissection only on the basis of clinical manifestations. Moreover, patients with type A dissection may have ECG changes caused by affection of the coronary flow.We retrospectively investigated all patients admitted to our hospital with type A dissection of the aorta over the period 1999 to March 2001.Fourteen patients were identified. Only two patients had normal ECG, six had ST elevation. Two patients had received antithrombotic or thrombolytic therapy.In patients with chest pain and ST elevation, aortic dissection must be considered as a differential diagnosis before thrombolytic therapy.

Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured blood pressure; insulin sensitivity by hyperinsulinaemic euglucaemic clamp; minimal forearm vascular resistance (MFVR) by plethysmography; intima-media cross-sectional area of the common carotid arteries (IMA) by ultrasound; and LV mass, relative wall thickness (RWT), systolic function and diastolic filling by echocardiography after two weeks of placebo treatment. LV mass index correlated to IMA/height (r=0.36, P=0.001), serum insulin (r=−0.25, P

The Carvedilol Acute Myocardial Infarction Study (CAMIS) investigates cardiac remodeling in patients (n = 250) randomized to carvedilol vs atenolol and treated for 12 months after acute myocardial infarction. In a sub-study, we compared sympathetic, hemorrheological and vascular effects in small but particularly well-matched groups of participants who had been on reasonably equipotent but unchanged doses of carvedilol (n = 10) or atenolol (n = 10) for at least 4 weeks. Blood pressures (p < 0.05), plasma adrenaline (p = 0.034), plasma vasopressin (p = 0.022) and whole blood viscosity at shear rate 0.5 cp (p = 0.050), 1.1 cp (p = 0.023), 5.8 cp (p = 0.049) and 201 cp (p = 0.060) taken in the laboratory at baseline before 2 h of using the hyperinsulinemic, isoglycemic glucose clamp were lower on carvedilol. Plasma noradrenaline was lower on carvedilol at baseline and throughout the clamp (p < 0.0005). Forearm vascular resistance as measured by plethysmography during the clamp tended to be lower on carvedilol (p = 0.074). No significant difference was found between the groups in glucose disposal rate measured by clamp, maximal forearm blood flow and minimal forearm vascular resistance after 10 min of ischemia, or in ambulatory blood pressure and heart rate taken a few days later. Thus, potential benefits of carvedilol vs atenolol were seen in these post-infarction patients in a laboratory setting. These findings suggest that the inhibitory effects on the sympathetic nervous system and related blood viscosity are stronger with carvedilol than with atenolol.

Home blood pressure (BP) monitoring has become popular in clinical practice and several automated devices for home BP measurement are now recommendable. Home BP is generally lower than clinic BP, and similar to daytime ambulatory BP. Home BP measurement eliminates the white coat effect and provides a high number of readings, and it is considered more accurate and reproducible than clinic BP. It can improve the sensitivity and statistical power of clinical drug trials and may have a higher prognostic value than clinic BP. Home monitoring may improve compliance and BP control, and reduce costs of hypertension management. Diagnostic thresholds and treatment target values for home BP remain to be established by longitudinal studies. Until then, home BP monitoring is to be considered a supplement. However, high home BP may support or confirm the diagnosis made in the doctor's office, and low home BP may warrant ambulatory BP monitoring. During long-term follow-up, home BP monitoring provides an opportunity for close attention to BP levels and variations. The first international guidelines have established a consensus document with recommendations, including a proposal of preliminary diagnostic thresholds, but further research is needed to define the precise role of home BP monitoring in clinical practice.

We have previously shown correlations between cardiovascular risk factors such as blood pressure (BP), sympathetic nervous system activity, lipids and insulin resistance in young men with elevated screening BP. In the present study we aimed to: (1) compare the genotype distribution and allele frequencies of 11 polymorphisms in seven candidate genes for BP regulation in healthy 21-year-old Caucasian men, between 18 men with normal and 67 men with high screening BP, and (2) evaluate the effect of these polymorphisms in candidate genes on casual BP, BP responses to mental stress or catecholamines and metabolic parameters including insulin sensitivity. There were no differences in genotype distributions or allele frequencies between the subjects with normal and those with high screening BP. Insulin sensitivity was significantly higher in GG homozygotes in the G-261A polymorphism at the alpha 2A-adrenergic receptor (alpha(2A)AR) locus compared to GA heterozygotes (p = 0.007). Subjects who were homozygous both GG in the G-261A polymorphism at the alpha(2A)AR locus and GlyGly in the Arg16Gly polymorphism at the beta2-adrenergic (beta2AR) receptor loci had significantly higher insulin sensitivity and lower catecholamine levels during mental stress than subjects with other genotypes. Subjects who were II homozygous at the angiotensin converting enzyme (ACE) locus and AA homozygous at the angiotensin type I receptor (AT1R) locus had lower BP and a better lipid profile than the rest of the group. Thus, in this explorative study, we report an association between insulin sensitivity and a polymorphism at the alpha(2A)AR locus. We suggest the presence of gene-gene interactions in the renin-angiotensin system and the sympathetic nervous system.