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S E Kjeldsen

Publications and source records attributed to S E Kjeldsen.

At least 19 recordsLinked to original sources
PubMed2001

[Are newer antihypertensive agents better than the older ones? Results of trials (CAPPP, STOP-2, NORDIL, INSIGHT and ALLHAT) with newer antihypertensive agents].

Until recently, no morbidity-mortality study had examined the effects of "newer" drugs, like angiotensin-converting enzyme inhibitors, calcium antagonists, and alpha-blockers compared to "old", but well-proven, thiazide diuretics, and beta-blockers in the treatment of essential hypertension. The prospective and randomised clinical trials, CAPPP, STOP-2, NORDIL, INSIGHT, and one arm of ALLHAT, with a total of about 58,000 middle-aged or elderly hypertensive patients have now been published. The primary outcome, composite cardiovascular (CV) death, cerebral stroke, and myocardial infarction, or composite fatal coronary heart disease and myocardial infarction, was the same, irrespective of the drug in all trials. Thus, prevention of CV complications depends on the lowering of blood pressure with well-tolerated medication, irrespective of class.

Adult↗
PubMed2001

[Comparison of preventive effect of "new" and "old" antihypertensive agents].

BACKGROUND: Until recently no morbidity-mortality study had examined the effects of newer drugs like angiotensin-converting enzyme inhibitors, calcium-antagonists and alpha-blockers compared to "old" but well-proven thiazide diuretics and beta-blockers in the treatment of essential hypertension. MATERIAL AND METHODS: The prospective and randomized clinical trials CAPPP, STOP-2, NORDIL, INSIGHT and one arm of ALLHAT, with a total of approximately 58,000 middle-aged or elderly hypertensive patients have been assessed. RESULTS: The primary outcome, composite cardiovascular (CV) death, cerebral stroke and myocardial infarction, in one study with heart failure, or composite fatal coronary heart disease and myocardial infarction, was equal in all trials. INTERPRETATION: According to current evidence, prevention of cardiovascular disease in hypertension is the same irrespective of the class of drug.

Adrenergic alpha-Antagonists↗
PubMed2001

Relationship of the electrocardiographic strain pattern to left ventricular structure and function in hypertensive patients: the LIFE study. Losartan Intervention For End point.

OBJECTIVES: This study was designed to assess the relation of electrocardiographic (ECG) strain to increased left ventricular (LV) mass, independent of its relation to coronary heart disease (CHD). BACKGROUND: The classic ECG strain pattern, ST depression and T-wave inversion, is a marker for left ventricular hypertrophy (LVH) and adverse prognosis. However, the independence of the relation of strain to increased LV mass from its relation to CHD has not been extensively examined. METHODS: Electrocardiograms and echocardiograms were examined at study baseline in 886 hypertensive patients with ECG LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage enrolled in the Losartan Intervention For End point (LIFE) echocardiographic substudy. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite to the QRS axis in leads V5 and/or V6. RESULTS: Strain occurred in 15% of patients, more commonly in patients with than without evident CHD (29%, 51/175 vs. 11%, 81/711, p < 0.001). When differences in gender, race, diabetes, systolic pressure, serum creatinine and high density lipoprotein cholesterol were controlled, strain on baseline ECG was associated with greater indexed LV mass in patients with (152 +/- 33 vs. 131 +/- 32 g/m2, p < 0.001) or without CHD (131 +/- 24 vs. 119 +/- 22 g/m2, p < 0.001). In logistic regression analyses, strain was associated with an increased risk of anatomic LVH in patients with CHD (relative risk 5.14, 95% confidence interval [CI] 1.16 to 22.85, p = 0.0315), without evident CHD (relative risk 2.91, 95% CI 1.50 to 5.65, p = 0.0016), and in the overall population when CHD was taken into account (relative risk 2.98, 95% CI 1.65 to 5.38, p = 0.0003). CONCLUSIONS: When clinical evidence of CHD is accounted for, ECG strain is likely to indicate the presence of anatomic LVH. Greater LV mass and higher prevalence of LVH in patients with strain offer insights into the known association of the strain pattern with adverse outcomes.

Aged↗
PubMed2001

Biphasic effect of epinephrine on blood glucose during hyperinsulinemia in borderline hypertensive young men.

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.

Adolescent↗
PubMed2001

Relation of echocardiographic left ventricular mass and hypertrophy to persistent electrocardiographic left ventricular hypertrophy in hypertensive patients: the LIFE Study.

BACKGROUND: The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) trial used left ventricular hypertrophy (LVH) on a screening ECG to identify patients at high risk for morbid events. Because of regression to the mean, not all patients who met screening criteria had persistent ECG LVH on the ECG performed at study baseline. METHODS: The relationship of echocardiographic LV mass and LVH to persistence or loss of ECG LVH between screening and baseline evaluation was examined in 906 hypertensive patients in the LIFE study, who had echocardiograms and additional ECG performed at study baseline. Patients were categorized according to the presence or absence of ECG LVH by Cornell voltage-duration product criteria or Sokolow-Lyon voltage criteria; echocardiographic LVH was defined by LV mass index (LVMI) > 104 g/m2 in women and > 116 g/m2 in men. RESULTS: A total of 678 patients (75%) had persistent ECG LVH at baseline evaluation. Compared with the 228 patients without ECG LVH on the second ECG by either criterion, the 106 patients with LVH by both Cornell product and Sokolow-Lyon criteria had significantly higher LVMI (140+/-31 v 114+/-21 g/m2, P < .001) and a higher prevalence of echocardiographic LVH (86% v 55%, P < .001). Patients with ECG LVH on the baseline ECG by either Cornell product criteria (n = 410) or Sokolow-Lyon voltage criteria (n = 162) had intermediate values of LVMI (125+/-25 and 121+/-21 g/m2) and prevalences of echocardiographic LVH (78% and 62%). After controlling for possible effects of age, sex, ethnicity, systolic blood pressure, and body mass index, persistence of ECG LVH on the baseline ECG was associated with an increased risk of echocardiographic LVH: compared with patients with neither ECG criteria for LVH, patients with only Sokolow-Lyon voltage criteria had a 1.2-fold increased risk of echocardiographic LVH, those with only Cornell product criteria had a 2.7-fold increased risk, and patients with both ECG criteria had a 4.1-fold increased risk of echocardiographic LVH (P < .001). CONCLUSIONS: Persistent ECG LVH between screening and LIFE study baseline identified patients with greater LV mass and a higher prevalence of echocardiographic LVH, suggesting that these patients may be at higher risk for subsequent morbid and mortal events.

Aged↗
PubMed2001

Glucose disposal rates calculated from 60- to 90-minute isoglycemic hyperinsulinemic glucose clamp correlate with cardiovascular risk factors in borderline hypertensive young men.

The hyperinsulinemic glucose clamp is generally performed for at least 120 minutes, due to assumptions of steady-state. We were interested in relationships between glucose disposal rate (GDR) and cardiovascular risk factors, rather than a standard measure of insulin sensitivity per se. Therefore, we analyzed 120-minute clamps performed on borderline hypertensive, but otherwise healthy young men (n = 19). GDR was calculated at different time points and related to baseline cardiovascular risk factors and responses to a mental stress test (MST). The 60-, 90-, and 120-minute GDR correlated significantly with serum high-density lipoprotein (HDL) cholesterol (r=.59, r=.50, and r=.53, respectively), heart rate (HR) during MST (r = -.65, r = -.64, and r = -.58, respectively) and plasma epinephrine (Epi) (r = -.55, r= -.58, and r = -.56, respectively) and norepinephrine (NE) (r = -.52, r = -.49, and r = -.48, respectively) 1 minute after announcement of the MST (all P <.05). Although not statistically significant at all time points, similar relationships were observed between GDR and resting HR, systolic blood pressure (BP) at rest and during mental stress, body mass index (BMI), serum total cholesterol (Chol), serum triglycerides (TG), and blood hemoglobin (HgB), with remarkable consistency from about 40 to 50 minutes onwards. HDL cholesterol and Epi remained independent in stepwise multiple regression analyses with the 60-, 90-, and 120-minute GDR as dependent variables (all P <.05). We suggest that 60- to 90-minute glucose clamps may provide information about the relationship between insulin sensitivity and various cardiovascular risk factors in borderline hypertensive young caucasian men.

Adult↗
PubMed2001

Characteristics of 15,314 hypertensive patients at high coronary risk. The VALUE trial. The Valsartan Antihypertensive Long-term Use Evaluation.

Valsartan is an orally active, selective antagonist of the angiotensin II-1 (AT1) receptor developed for the treatment of hypertension. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) Trial of Cardiovascular Events in Hypertension is a double-blind, randomized prospective, parallel group study designed to compare the effects of valsartan with those of the calcium-antagonist amlodipine on the reduction of cardiac morbidity and mortality. Patients with essential hypertension, aged 50 years and older, and at particularly high risk of coronary events were enrolled. 18,119 patients were screened and 15,314 patients in 31 countries were randomized mainly between January 1998 and December 1999. These hypertensives had a mean blood pressure of 154.7/87.5 mmHg at the time of their randomization to blinded medication. The population comprises both genders (men 57.6%), Caucasians (89.1%), mean age 67.2 years, mean body mass index 28.6 kg/m2, coronary heart disease (45.8%), high cholesterol (33.0%), type 2 diabetes mellitus (31.7%) and smokers (24.0%). More than 92% of the randomized participants had been treated for high blood pressure for at least 6 months when screened for the study. The randomized population is now being treated (goal blood pressure < 140/90 mmHg) in adherence with the protocol until at least 1450 patients experience primary cardiac endpoint defined as clinically evident or aborted myocardial infarction, hospitalization for heart failure or death caused by coronary heart disease.

Aged↗
PubMed2001

Polymorphisms in candidate genes for blood pressure regulation in young men with normal or elevated screening blood pressure.

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.

Adult↗
PubMed2001

Home blood pressure monitoring. Current knowledge and directions for future research.

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.

Blood Pressure Determination↗
PubMed2001

Gender specific sympathetic and hemorrheological responses to mental stress in healthy young subjects.

OBJECTIVE: Activation of the sympathetic nervous system may increase hematocrit (Hct), whole blood viscosity (WBV), and possibly cardiovascular risk. The aim was to study gender specific differences of mental stress on sympathetic reactivity and blood rheology. METHODS: Responses in blood pressure, heart rate (HR), Hct, WBV (Bohlin rotational viscosimeter), and plasma catecholamines to a mental arithmetic stress test (MST) were measured in male (n = 10, 23 +/- 3 years, BMI 23 +/- 2 kg/m2) and female (n = 10, 21 +/- 4 years, BMI 24 +/- 2 kg/m2) students. RESULTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR increased during MST in men and women, and declined to baseline levels after 15 min of recovery. In men, plasma adrenaline increased by 217% during MST (p < 0.01, ANOVA). and plasma noradrenaline increased by 68% (p < 0.05). Hct and WBV at low shear rates (0.5 and 1.1 l/s) increased as well (p < 0.001, p < 0.05, and p < 0.05, respectively). In women, the increase in plasma adrenaline averaged 118% during MST (p < 0.05) while plasma noradrenaline (-3%, p = 0.38), Hct, and WBV at all shear rates remained unchanged. Men and women differed in A adrenaline (p < 0.05), A noradrenaline (p = 0.01), delta Hct (p < 0.05), and delta WBV (p < 0.05). A Hct tended to correlate with delta SBP (r= 0.60, p = 0.07), A DBP (r = 0.57. p = 0.09). and delta HR (r = 0.50, p = 0.14), and correlated significantly with A noradrenaline (r = 0.66, p < 0.05) in men only. Multiple regression analysis showed that gender independently explained 22% of the change in Hct during mental stress. CONCLUSION: Data suggest gender specific differences in sympathetic and hemorrheological responses to mental stress in healthy young subjects. In men, sympathetic responses were related to hemorrheological responses, but not in women. It may be speculated whether such differences in stress responses may contribute to lower cardiovascular risk in premenopausal women than in men.

Adult↗
PubMed2001

Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.

OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.

Adrenergic beta-Antagonists↗
PubMed2001

Supine and exercise systolic blood pressure predict cardiovascular death in middle-aged men.

AIM AND METHODS: The outcome of 1999 apparently healthy men, aged 40-59 years, initially investigated in the period 1972-1975, has previously been ascertained at 7 and 16 year follow-ups. This has now been repeated after 21 years, to determine whether seated systolic blood pressure (BP) during a bicycle ergometer exercise test adds prognostic information on cardiovascular (CV) mortality beyond that of systolic BP measured after 5 min of supine rest. RESULTS: After 21 years, 41 979 years of observation, 470 patients had died, 255 from CV causes. Supine systolic BP [2 SD increase: relative risk (RR) 1.6, 95% confidence interval (CI) 1.3-2.0, P < 0.0001], 6 min exercise systolic BP (2 SD increase: RR 1.6, 95% CI 1.3-2.0, P < 0.0001) on the starting workload of 600 kpm/min (approximately 100 W, 5880 J/min) and maximal systolic BP (2 SD increase: RR 1.5, 95% CI 1.2-1.9, P = 0.0005) during work were all related to CV mortality when adjusting for a large number of variables measured in the present study including age, exercise capacity, heart rates, smoking habits, glucose tolerance and serum cholesterol. When including other systolic BPs in the continuous multivariate analysis, supine systolic BP (2 SD increase: RR 1.4, 95% CI 1.04-1.9, P = 0.029) and 6 min systolic BP at 600 kpm/min (2 SD increase: RR 1.4, 95% CI 1.06-1.9, P = 0.017) were independent predictors of CV death but not maximal systolic BP during exercise (2 SD increase: RR 1.0, 95% CI 0.7-1.2, P = 0.95). CONCLUSION: These results are different from the mortality data at 16 years, when the independent predictive effect of supine systolic BP was cancelled out by 6 min exercise systolic BP at 600 kpm/min. Twenty-one years of follow-up of 1999 apparently healthy men disclose independently predictive information on CV death, of both supine systolic BP and 6 min exercise systolic BP taken at an early moderate workload. The influence of maximal exercise systolic BP on CV death is however cancelled out by the two other systolic BPs.

Adult↗
PubMed2000

Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study.

BACKGROUND: Calcium antagonists are a first-line treatment for hypertension. The effectiveness of diltiazem, a non-dihydropyridine calcium antagonist, in reducing cardiovascular morbidity or mortality is unclear. We compared the effects of diltiazem with that of diuretics, beta-blockers, or both on cardiovascular morbidity and mortality in hypertensive patients. METHODS: In a prospective, randomised, open, blinded endpoint study, we enrolled 10,881 patients, aged 50-74 years, at health centres in Norway and Sweden, who had diastolic blood pressure of 100 mm Hg or more. We randomly assigned patients diltiazem, or diuretics, beta-blockers, or both. The combined primary endpoint was fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death. Analysis was done by intention to treat. FINDINGS: Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups (reduction 20.3/18.7 vs 23.3/18.7 mm Hg; difference in systolic reduction p<0.001). A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group (16.6 vs 16.2 events per 1000 patient-years; relative risk 1.00 [95% CI 0.87-1.15], p=0.97). Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group (6.4 vs 7.9 events per 1000 patient-years; 0.80 [0.65-0.99], p=0.04) and fatal and non-fatal myocardial infarction in 183 and 157 patients (7.4 vs 6.3 events per 1000 patient-years; 1.16 [0.94-1.44], p=0.17). INTERPRETATION: Diltiazem was as effective as treatment based on diuretics, beta-blockers, or both in preventing the combined primary endpoint of all stroke, myocardial infarction, and other cardiovascular death.

Adrenergic beta-Antagonists↗