Prognostic importance of hemoglobin in hypertensive patients with electrocardiographic left ventricular hypertrophy: the Losartan Intervention For End point reduction in hypertension (LIFE) study.

BACKGROUND: The prognostic importance of hemoglobin is controversial. We investigated the prognostic importance of baseline and in-treatment hemoglobin in the LIFE study. METHODS: Eight thousand one hundred ninety-four LIFE patients with hypertension and left ventricular hypertrophy with available baseline hemoglobin measurements were randomized to losartan- or atenolol-based treatment and followed for 4.8 years for end points of all-cause mortality and composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. RESULTS: U-shaped relations were observed between deciles of baseline hemoglobin and all-cause mortality and the composite end point. In univariate Cox models, baseline hemoglobin in the lowest gender-specific decile (women/men: <12.5/13.4 g/dL) was associated with all-cause mortality (hazard ratio [HR] 2.01, 95% CI 1.64-2.64) and the composite end point (HR 1.53, 95% CI 1.27-1.85, both P < .001), whereas hemoglobin in the highest gender-specific decile (women/men: > or =15.0/16.2 g/dL) was not. The decrease in hemoglobin was higher (P < .001) in patients allocated to losartan- (14.3-13.8 g/dL) versus atenolol-based treatment (14.3-14.0 g/dL). In Cox models with the same gender-specific definitions for high and low hemoglobin as time-varying covariates with adjustment for treatment allocation and established risk factors and diseases, hemoglobin in the lowest decile was associated with higher rates of all-cause mortality (HR 3.03, 95% CI 1.89-4.85, P < .001) and the composite end point (HR 1.36, 95% CI 1.08-1.71, P < .01), whereas hemoglobin in the highest decile was not. CONCLUSIONS: After adjusting for other risk factors, relatively low, but not high, hemoglobin during antihypertensive treatment was associated with higher incidence of all-cause mortality and the composite end point.

Left ventricular diastolic function in patients with treated haemochromatosis.

OBJECTIVES: We recently demonstrated reduced exercise capacity in phlebotomy treated genetic haemochromatosis in spite of normal systolic function. The present objective was to investigate diastolic function at rest. DESIGN: Diastolic function was echocardiographically assessed in 132 phlebotomy treated genetic haemochromatosis patients and 50 controls. RESULTS: Patients had higher body mass index and heart rate, higher transmitral early (E) (11.2+/-2.6 versus 10.4+/-2.2 cm) and atrial (A) (5.7+/-1.6 versus 5.0+/-1.6) velocity time integrals, pulmonary venous systolic peak velocity (0.58+/-0.12 versus 0.54+/-0.13 m/s) and ratio of E to spectral tissue Doppler E' velocity (6.3+/-1.6 versus 5.6+/-1.4, all p <0.05). Independently of age, heart rate, systolic blood pressure and body weight, having haemochromatosis remained statistically significantly associated with higher E (beta=0.27) and A (beta =0.18) velocity time integrals, pulmonary venous systolic peak velocity (beta =0.21), and E/E'-ratio (beta=0.25) in separate multivariate analyses (all p <0.05). In the youngest age tertile, patients had longer isovolumic relaxation time and lower E' than controls. CONCLUSION: Our findings are compatible with mildly impaired diastolic function in treated haemochromatosis, with delayed relaxation in the younger tertile, and an elevated filling pressure and pseudonormalisation with increasing age.

Predictors of cardiovascular events in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention for Endpoint reduction in hypertension study.

OBJECTIVE: We assessed readily available patient characteristics, including albuminuria (not included in traditional cardiovascular risk scores), as predictors of cardiovascular events in hypertension with left ventricular hypertrophy (LVH) and developed risk algorithms/scores for outcomes. METHODS: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study compared effects of losartan-based versus atenolol-based therapy on cardiovascular events in 9193 patients with hypertension and LVH. Univariate and multivariate analyses identified baseline variables with significant impact on development of the primary composite endpoint (cardiovascular death, stroke and myocardial infarction) and its components. Multivariate analysis used a Cox regression model with stepwise selection process. Risk scores were developed from coefficients of risk factors from the multivariate analysis, validated internally using naïve and jack-knife procedures, checked for discrimination and calibration, and compared with Framingham coronary heart disease and other risk scores. RESULTS: LIFE risk scores showed increasing endpoint rates with increasing quintile (first to fifth quintile, composite endpoint 2.8-26.7%, cardiovascular death 0.5-14.4%, stroke 1.2-11.3%, myocardial infarction 1.4-8.1%) and were confirmed with a jack-knife approach that adjusts for potentially optimistic bias. The Framingham coronary heart disease and other risk scores overestimated risk in lower risk patients and underestimated risk in higher risk patients, except for myocardial infarction. CONCLUSION: A number of patient characteristics predicted cardiovascular events in patients with hypertension and LVH. Risk scores developed from these patient characteristics, including albuminuria, strongly predicted outcomes and may improve risk assessment of patients with hypertension and LVH and planning of clinical trials.

Body build and risk of cardiovascular events in hypertension and left ventricular hypertrophy: the LIFE (Losartan Intervention For Endpoint reduction in hypertension) study.

BACKGROUND: Obesity may independently increase the risk of adverse events in hypertension with target-organ damage. We investigated whether body build was independently associated with higher cardiovascular risk and whether treatment with losartan relative to atenolol influenced the impact of body build on the primary composite end point of cardiovascular death, stroke, and myocardial infarction and on cardiovascular death in patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. METHODS AND RESULTS: The population of 9079 patients was divided as follows: thin (body mass index [BMI] <20 kg/m2, 2%), normal weight (BMI 20 to 24.9, 24%), overweight (BMI 25 to 29.9, 45%), and obese (class I: BMI 30 to 34.9, 21%; class II: BMI 35 to 39.9, 6%; class III: BMI > or =40, 2%). Incident diabetes increased progressively with BMI and was somewhat higher in the atenolol arm. Differences in gender and race were detected among the body build groups. Rates (Cox proportional hazard analysis) of the primary composite end point did not differ among body build groups after adjustment for age, gender, race, smoking habit, prevalent cardiovascular disease, and left ventricular hypertrophy. Cardiovascular death was more frequent among thin (P<0.05) and pooled class II-III obesity (both P<0.04) than normal-weight groups. Risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan- as opposed to atenolol-based treatment. CONCLUSIONS: In the LIFE study, stratification for classes of body build identified increased risk of cardiovascular mortality in both thin and moderately-to-severely obese individuals. This risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan-based treatment as opposed to atenolol-based 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.

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Targeting the renin-angiotensin system for the reduction of cardiovascular outcomes in hypertension: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

Agents that counteract the negative impact of the renin-angiotensin-aldosterone system (RAAS) are effective antihypertensives and reduce the risk of developing Type 2 diabetes. Contrary to common perception, angiotensin-converting enzyme inhibitors do not share the apparent benefit of angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular-disease outcomes, particularly stroke, in randomised clinical trials. RAAS agents, especially ARBs, are well tolerated. Use of ARBs alone or in combination with other classes of antihypertensive agents to lower blood pressure and/or medications to control other conditions (e.g., insulin sensitivity) reduces risk of cardiovascular disease outcomes and Type 2 diabetes with excellent tolerability. Selected issues related to use of RAAS agents as antihypertensive therapies (e.g., Type 2 diabetes, global risk management, multiple drug therapy and coronary heart disease) are addressed.

The effects of losartan compared to atenolol on stroke in patients with isolated systolic hypertension and left ventricular hypertrophy. The LIFE study.

The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study reported that a losartan-based antihypertensive regimen reduced cardiovascular morbidity and mortality (composite of cardiovascular death, stroke, and myocardial infarction) more than therapy based on atenolol in patients with left ventricular hypertrophy and isolated systolic hypertension (ISH). Patients aged 55-80 years with blood pressures 160-200/<90 mm Hg were followed for a mean of 4.7 years. Blood pressure was similarly reduced in the losartan (n=660) and atenolol (n=666) ISH groups. There were 88 (6.6%) patients who experienced a stroke, 18 of which were fatal. Of patients experiencing strokes, 72.7% had an ischemic stroke. ISH patients in LIFE compared to the non-ISH group had a higher incidence of any stroke and embolic stroke, and similar incidences of fatal, atherosclerotic, and hemorrhagic/other strokes. The incidence of any stroke (40% risk reduction [RR], p=0.02), fatal stroke (70% RR, p=0.035), and atherothrombotic stroke (45% RR, p=0.022) was significantly lower in losartan-treated compared to the atenolol-treated patients. The 36% RR for embolic strokes in the losartan group was not statistically significantly (p=0.33) different from the atenolol group. These data suggest that losartan-based treatment is more effective than an atenolol-based treatment for patients with ISH and a high risk for stroke.

Effects of losartan or atenolol in hypertensive patients without clinically evident vascular disease: a substudy of the LIFE randomized trial.

BACKGROUND: Cardiovascular morbidity and mortality are reduced by treatment with the angiotensin II AT(1)-receptor antagonist losartan compared with conventional treatment with the beta-blocker atenolol in patients with hypertension and electrocardiogram-defined left ventricular hypertrophy, many of whom had known vascular disease. OBJECTIVE: To determine whether losartan reduces cardiovascular event rates in lower-risk hypertensive patients without clinically evident vascular disease. DESIGN: Subgroup analysis of a randomized trial. SETTING: The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study. PATIENTS: 6886 men and women (57% women) 55 to 80 years of age (average, 66 years) with essential hypertension (sitting blood pressure, 160 to 200/95 to 115 mm Hg [average, 174/98 mm Hg]) and electrocardiogram-defined left ventricular hypertrophy who did not have clinically evident vascular disease. INTERVENTION: Patients were randomly assigned to once-daily double-blind treatment with losartan or atenolol. MEASUREMENTS: An end point committee ascertained end points (cardiovascular death, stroke, or myocardial infarction). RESULTS: Blood pressure was reduced similarly by losartan and atenolol. The primary composite end point occurred in 282 losartan-treated patients (17.5 per 1000 patient-years) and 355 atenolol-treated patients (21.8 per 1000 patient-years; relative risk, 0.81 [95% CI, 0.69 to 0.95]; P = 0.008). Cardiovascular death occurred in 103 losartan-treated patients and 132 atenolol-treated patients (relative risk, 0.80 [CI, 0.62 to 1.04]; P = 0.092), stroke (nonfatal and fatal) occurred in 125 losartan-treated patients and 193 atenolol-treated patients (relative risk, 0.66 [CI, 0.53 to 0.82]; P < 0.001), and myocardial infarction (nonfatal and fatal) occurred in 110 losartan-treated patients and 100 atenolol-treated patients (relative risk, 1.14 [CI, 0.87 to 1.49]; P > 0.2). New-onset diabetes occurred less often in patients treated with losartan (n = 173) than in patients treated with atenolol (n = 254) (relative risk, 0.69 [CI, 0.57 to 0.84]; P < 0.001). Benefits of losartan treatment were numerically smaller, but not significantly so, in patients with preexisting vascular disease. CONCLUSION: In hypertensive patients without clinically evident vascular disease, losartan was more effective than atenolol in preventing cardiovascular morbidity and death, predominantly stroke, independent of blood pressure reduction.

Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study.

BACKGROUND: Several studies have shown that albuminuria is associated with increased risk for fatal and nonfatal cardiovascular events, independent of conventional risk factors. The partition values for urine albumin-creatinine ratio (UACR) used to identify microalbuminuria have been based on studies that predicted risk in diabetic patients. OBJECTIVE: To determine whether the relation between albuminuria and cardiovascular risk can be used to predict cardiovascular morbidity and mortality in hypertensive patients. DESIGN: Multicenter cohort study derived from a randomized, controlled trial. PATIENTS: 8206 patients with stage II or III hypertension randomly assigned to double-blind therapy with losartan or atenolol. Follow-up was 39 122 patient-years. MEASUREMENTS: Renal glomerular permeability evaluated by UACR. RESULTS: In nondiabetic hypertensive patients with left ventricular hypertrophy, the risk for the composite cardiovascular end point increased continuously as albuminuria increased (P < 0.001 for trend). There was no specific threshold for increased risk. For every 10-fold increase in UACR, hazard ratios in nondiabetic patients increased as follows: composite end point, by 57% (95% CI, 40.6% to 75.0%); cardiovascular mortality, by 97.7% (CI, 66.5% to 235%); all-cause mortality, by 75.2% (CI, 54.0% to 99.4%); stroke, by 51.0% (CI, 28.8% to 76.9%); and myocardial infarction, by 45% (CI, 19.9% to 75.4%) (P < 0.001 for all comparisons). Values were similar in diabetic patients, although for myocardial infarction the trend was weaker and not significant. CONCLUSION: Increased UACR resulted in increasing risk for cardiovascular morbidity and mortality among hypertensive patients with left ventricular hypertrophy. We found no thresholds or plateaus. Risk increases at much lower UACR values than has been reported among diabetic patients.

Impact of diastolic Doppler indices on exercise capacity in hypertensive patients with electrocardiographic left ventricular hypertrophy (a LIFE substudy).

OBJECTIVE: To assess whether Doppler evidence of impaired early diastolic relaxation during exercise is associated with lesser exercise capacity in hypertensive patients. DESIGN: Single center addition to the echocardiographic substudy in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. SETTING: University hospital out-patient clinic. METHODS: A total of 60 patients (29 women and 31 men) with essential hypertension and electrocardiographic LV hypertrophy. INTERVENTIONS: Assessment of Doppler echocardiography and ergospirometry during semi-upright bicycling. MAIN OUTCOME MEASURE: Exercise capacity and its relation to diastolic Doppler indices at rest and during exercise. RESULTS: Average resting blood pressure was 181/97 +/- 18/9 mmHg, LV mass/body surface area 127 +/- 26 g/m2, midwall shortening 16 +/- 2%, and isovolumic relaxation time (IVRT) and transmitral early to atrial filling velocity (E/A) ratio 121 ms and 0.80, respectively. Exercise capacity, assessed as peak oxygen uptake and exercise load at exhaustion in all patients, were 20 and 25% higher, respectively, in men than women (both P < 0.01). In multivariate analysis, higher peak exercise load was related to male gender, higher E/A ratio at rest, greater reduction in IVRT during exercise and higher peak exercise heart rate (multiple R2 = 0.59, P < 0.01). Younger age, greater reduction in IVRT during exercise, higher midwall shortening and peak exercise heart rate were associated with higher peak oxygen uptake (multiple R2 = 0.47, P < 0.01). CONCLUSION: Diastolic LV performance significantly influences exercise capacity in hypertensive patients with LV hypertrophy. Impaired exercise capacity is more strongly associated with blunted reduction in IVRT during exercise than with lower E/A ratio at rest.

Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy.

OBJECTIVES: To examine a possible relationship between baseline albuminuria and effect of losartan versus atenolol on cardiovascular (CV) events in hypertensive patients with left ventricular hypertrophy, the effect of losartan versus atenolol on albuminuria, and whether the benefits of losartan versus atenolol could be explained by influence of losartan on albuminuria. DESIGN: Double-blind, randomized, controlled trial of 4.8 years. SETTING: Out-patient setting. PATIENTS: A total of 8206 with hypertension and left ventricular hypertrophy. INTERVENTIONS: Losartan or atenolol, supplemented with diuretics and/or calcium antagonists to reach blood pressure < 140/90 mmHg MAIN OUTCOME MEASURES: The urine albumin/creatinine ratio, and the primary composite endpoint (CEP) of CV death, myocardial infarction, and stroke. RESULTS: The blood pressure was reduced similarly on losartan (30.2/16.6 mmHg) versus atenolol (29.1/16.8 mmHg). The risk of a primary CEP increased linearly from the lowest to the highest decile of baseline albuminuria. The benefits of losartan versus atenolol for the primary CEP and for stroke tended to be more pronounced among patients above the median value for baseline albuminuria (urine albumin/creatinine ratio, 1.28 mg/mmol). The decrease in albuminuria was significantly greater with losartan versus atenolol throughout the study (a decrease from baseline to year 2 of 33% losartan versus 25% atenolol). One-fifth of the difference in favor of losartan on the primary CEP was explained by the greater reduction in albuminuria on losartan. CONCLUSIONS: Baseline albuminuria is a powerful risk factor for CV events. Baseline albuminuria did not identify the group of patients with greatest benefit on losartan versus atenolol in LIFE. Reduction in albuminuria explained one-fifth of the benefits of losartan versus atenolol.

Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study.

BACKGROUND: There has been uncertainty about the risk of new-onset diabetes in hypertensive individuals treated with different blood pressure-decreasing drugs. OBJECTIVES: To study this risk in hypertensive individuals who were at risk of developing diabetes mellitus in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. METHODS: In the LIFE study, with a double-masked, randomized, parallel-group design, 9193 patients (46% men) with hypertension (mean age 67 years, average pressure 174/98 mmHg after placebo run-in) and electrocardiogram-documented left ventricular hypertrophy were randomly assigned to once-daily losartan- or atenolol-based antihypertensive treatment and followed for at least 4 years (mean 4.8 years). At baseline, 7998 patients did not have diabetes mellitus and were thus at risk of developing this condition during the study. To demonstrate ability to predict new-onset diabetes, we developed a prediction score using the significant variables from multivariate analyses (serum glucose, body mass index, serum high-density lipoprotein cholesterol, systolic blood pressure and history of prior use of antihypertensive drugs). RESULTS: There was a steadily increasing risk of diabetes with increasing level-of-risk score; patients in the highest quartile were at considerably greater risk than those in the three lower ones. Treatment with losartan was associated with lower risk of development of diabetes within each of the four quartiles of the risk score. As previously reported, new-onset diabetes mellitus occurred in 242 patients receiving losartan (13.0 per 1000 person-years) and 320 receiving atenolol (17.5 per 1000 person-years); relative risk 0.75 (95% confidence interval 0.63 to 0.88; P<0.001). CONCLUSIONS: New-onset diabetes could be strongly predicted by a newly developed risk score using baseline serum glucose concentration (non-fasting), body mass index, serum high-density lipoprotein cholesterol concentration, systolic blood pressure and history of prior use of antihypertensive drugs. Independently of these risk factors, fewer hypertensive patients with left ventricular hypertrophy developed diabetes mellitus if they were treated with losartan than if they were treated with atenolol.

Equal Efficacy and Improved Tolerability with 50 mg Controlled-Release Metoprolol Compared with 100 mg Conventional Metoprolol in Hypertensive Patients.

The clinical efficacy and tolerability of 50 mg of a new controlled-release formulation of metoprolol (metoprolol CR) was compared with that of a double dose (100 mg) of conventional immediate-release metoprolol tablets in 64 hypertensives in a randomized, double-blind, crossover study. At the end of a 6-week placebo run-in period and after each of two 8-week active treatment periods, 3-min bicycle exercise tests were performed at 25, 1.3, and 5 h after dose intake. Twenty-five hours after dose the mean supine SBP/DBP on metoprolol CR 50 mg was 147/95 mm Hg and on conventional metoprolol 100 mg 148/94 mm Hg, respectively. The percentage of responders (DBP less-than-or-equal 90 mm Hg or reduction in DBP greater-than-or-equal 10 mm Hg) was 45% on both regimens. At 25 h after dose, exercise heart rate was lower on 50 mg metoprolol CR (136 versus 140 beats min(minus sign1); p < 0.001) than on 100 mg conventional metoprolol, whereas the opposite was found at 1.3 h (131 versus 107 beats min(minus sign1); p < 0.001) and at 5 h (131 versus 113 beats min(minus sign1); p < 0.001). In agreement with the more even plasma metoprolol concentration and exercise heart rate, the patients perceived less fatigue during exercise on 50 mg metoprolol CR at 1.3 h after dose, the approximate time of maximum plasma concentration for 100 mg conventional metoprolol. The total number of adverse events recorded on metoprolol CR 50 mg and conventional metoprolol 100 mg were 62 and 103, respectively (p < 0.01). Thus, this study has demonstrated that the new controlled-release formulation of metoprolol has made it possible to halve the dose of metoprolol and yet achieve the same blood pressure control as well as greater beta(1)-blockade at the end of 24-h dosing intervals. Corresponding to lower peak plasma metoprolol concentrations, perceived fatigue and overall tolerability was improved on metoprolol CR 50 mg compared to conventional metoprolol 100 mg.

Long-Term Haemodynamic Effects of Enalapril at Rest and During Exercise in Essential Hypertension.

Twelve males with moderately severe essential hypertension (mean arterial pressure [MAP] ranging 113-162 mmHg) were studied at rest supine and sitting and during bicycle exercise (50, 100 and 150 W). Intraarterial blood pressure (BP), and heart rate (HR) were recorded continuously. Cardiac output (CO) was measured by dye dilution (Cardiogreen). After 6-8 months (enalapril dose 10-40 mg daily) patients were restudied. BP fell in all patients, at rest sitting from 184/107 mmHg to 150/87 (-19%) and during 100 W from 223/117 to 194/98 mmHg (p < 0.001). Pretreatment total peripheral resistance index (TPRI) was greatly increased in all patients and fell from 4137 to 3651 dyn s cm-5 m2 (-16%) (p < 0.05). No significant changes were seen in CO, HR or stroke volume. No side effects were seen. It is concluded that enalapril reduces BP in patients with moderately severe hypertension at rest and during exercise due to reduction in TPRI without significant changes in CO or HR.

Twenty-four-hour ambulatory blood pressure monitoring in atrial fibrillation.

BACKGROUND: Due to large beat-to-beat blood pressure variation the use of 24-h ambulatory blood pressure monitoring in patients with atrial fibrillation has been questioned. METHODS: Repeatability and variability of 24-h ambulatory blood pressure (Accutraccer II or Diasys Integra), and daily blood pressure variation was examined in 42 patients aged 51-81 (median 73.5) years admitted for elective electrocardioversion of atrial fibrillation. RESULTS: Before cardioversion 24-h ambulatory systolic blood pressure was slightly lower and nocturnal blood pressure reduction was larger in the group of patients who achieved sinus rhythm than in the group who maintained atrial fibrillation (11.5/10.5 versus 4.1/4.7 mmHg; P < 0.05). No statistically significant change was observed in ambulatory blood pressure after cardioversion in any of the two groups. Blood pressure variability (SD/mean) was 10-14% both in patients with and without conversion to sinus rhythm. Coefficient of repeatability (2 SD of difference) was 13.6 mmHg (16.6%) for diastolic blood pressure and 30.2 mmHg (24.7%) for systolic blood pressure in patients with normalized heart rhythm and 17.0 and 29.0 mmHg (21.5 and 22.4%) in patients with maintained atrial fibrillation, respectively. CONCLUSION: Ambulatory blood pressure monitoring provides data with similar variability and repeatability in patients with atrial fibrillation as in subjects with normal cardiac rhythm. Twenty-four-hour ambulatory blood pressure measurement is applicable in atrial fibrillation in the same way as during sinus rhythm.

Blood pressure measurements by the Keito machine. Evaluation versus office blood pressure by physicians.

BACKGROUND: The Keito machine offers automatic measurements of blood pressure (BP), height and weight on insertion of coins and has been introduced in pharmacies. DESIGN: Cross-sectional study comparing automatic BP measurements by the Keito machine to office BP measurements by physicians. METHODS: Patients scheduled for pre-catheterisation screening participated in the study. Their BP was first measured using the Keito machine, then by physicians. Office BP was recorded as the last of three consecutive BP measurements recorded with one-min intervals after a five-min rest in the sitting position. In a sub-study BP was measured simultaneously during the Keito measurement by a physician. RESULTS: In 390 consecutive patients average BP was significantly lower with the Keito machine compared to office BP measurements made by the physicians (136/75+/-19/8 mmHg versus 141/79+/-21/10 mmHg, both p<0.001). The correlation coefficient (r) was 0.56 (p<0.001) for systolic BP (SBP) and 0.53 (p<0.001) for diastolic BP (DBP). Bland-Altman analysis showed a mean difference (+/-2 SD) for SBP and DBP of -5 (+/-37) and -4 (+/-17) mmHg, respectively. When defining hypertension (HT) as office SBP> or =140 and/or DBP> or =90 mmHg, the Keito method diagnosed 83% of the systolic and 62% of the diastolic hypertensive population correctly. The classification of systolic and diastolic normotensive was correct in 61% and 86%, respectively. CONCLUSION: Agreement between office and Keito BP is poor. The Keito machine underestimates SBP on average by 5 mmHg and DBP by 4 mmHg, which may be of significance for diagnosing HT and starting anti-hypertensive therapy. However, the difference can be much larger in individual patients. Therefore, the Keito machine cannot be recommended for medical screening of HT or as a replacement for follow-up by physicians.

[Why not always diuretics?]. / Hvorfor ikke alltid diuretika?

BACKGROUND: New guidelines adopted in Norway for antihypertensive medication implies prescription of a thiazide diuretic as the drug of first choice. The background for the change in the rules for prescription drugs paid for by the National Insurance system with a capped co-payment is a resolution of the Norwegian parliament as part of a budget compromise for 2004. The resolution was supported by results from the ALLHAT study (antihypertensive and lipid-lowering treatment to prevent heart attack trial). METHODS: ALLHAT was carried out in a group of elderly, high-risk patients with a large proportion of Afro-Americans. RESULTS AND INTERPRETATION: ALLHAT has important shortcomings with regard to design, results, analysis and interpretation. The trial is considered unfit as a basis for general guidelines on antihypertensive treatment in Norway.

[Hypertension and heart disease]. / Hypertensjon og hjertesykdom.

Hypertension commonly leads to heart disease, in particular left ventricular hypertrophy, heart failure and coronary artery disease. Left ventricular hypertrophy and coronary artery disease are both often subclinical diseases in hypertensives. Symptomatic coronary artery disease in hypertension may be due to atherosclerosis in epicardial arteries, microvascular dysfunction, reduced fibrinolytic capacity, or left ventricular hypertrophy; the latter is present in 20-50% of patients with mild to moderate and in up to 90% of patients with severe hypertension. Left ventricular hypertrophy in hypertension is associated with a twofold increase in risk of myocardial infarction, sudden death and stroke, and a fourfold increase in risk of heart failure. While coronary artery disease is the most common cause of heart failure in men, hypertension and in particular untreated isolated systolic hypertension is the most common cause in women. Heart failure symptoms may be subtle in hypertension, like tiredness or reduced physical capacity. Echocardiography can reveal subclinical heart disease as well as serve as a guide to correct diagnosis and treatment.

[Treatment of hypertension in patients with left ventricular hypertrophy]. / Behandling av høyt blodtrykk hos pasienter med venstre ventrikkel-hypertrofi.

BACKGROUND: The LIFE study (Losartan Intervention For Endpoint reduction in hypertension) is a randomized, double-blind comparison of losartan and atenolol-based treatment. The study hypothesis was that losartan would reduce cardiovascular morbidity and mortality more than traditional antihypertensive treatment with atenolol. MATERIAL AND METHODS: The study included 9193 patients in seven countries. RESULTS: By the end of the study, the mean dose was losartan 82 mg and atenonol 79 mg, whereas 94% of patients in both groups received additional hydrochlorothiazide. Blood pressure was reduced 30/17 mmHg by losartan and 29/17 mm Hg by atenolol. Despite the same reduction in blood pressure, the primary combined endpoint (cardiovascular mortality, non-fatal stroke and myocardial infarction) was reduced by 13.0% (p = 0.021) in the losartan group. Non-fatal and fatal strokes were reduced by 24.9% (p = 0.001). In two pre-specified subgroup analyses, cardiovascular mortality was reduced by 46% (p = 0.01) in patients with isolated systolic hypertension (n = 1326), and total mortality was reduced by 39% (p = 0.002) in patients with diabetes (n = 1159). INTERPRETATION: Losartan prevented more cardiovascular complications than atenolol for the same reduction in blood pressure and have positive additional effects beyond blood pressure control in patients with hypertension and left ventricular hypertrophy.

Contrasting hemodynamic mechanisms of losartan- vs. atenolol-based antihypertensive treatment: a LIFE study.

BACKGROUND: Pharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP). METHODS: Data from all patients with at least two echocardiographic examinations in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) echocardiographic substudy (n = 801); high-risk patients on losartan- vs. atenolol-based antihypertensive therapy. Echocardiography was performed annually for 4 years to measure stroke index (SI), heart rate, cardiac index (CI), conduit artery stiffness assessed as pulse pressure/stroke index (PP/SI) and total peripheral resistance index (TPRI). RESULTS: Atenolol- and losartan-based therapy reduced BP similarly (cumulative difference in mean brachial blood pressure 0.3 mm Hg, P = 0.65). After 4 years the cumulative means of SI and heart rate were 1.8 ml/m(2) higher and 5.7 beats/min lower on atenolol-based treatment, respectively (both P < 0.001). This kept CI below baseline in atenolol-treated patients, whereas in the losartan group CI was unchanged from baseline throughout the study. TPRI was decreased more and remained lower in the losartan group (cumulative difference in mean TPRI 287 dynes/sec(-5)/cm/m(2), P < 0.001). These findings partly explained univariate differences in systolic- and diastolic function indices between the two treatments; fully adjusted losartan was only associated with a smaller left atrial diameter (cumulative mean difference 0.07 cm; 95% confidence intervals, -0.13 to -0.01, P = 0.03). CONCLUSIONS: Contrasting hemodynamics impacted cardiac response to similar reductions in brachial BP on losartan- vs. atenolol-based therapy. The similar reduction of PP/SI suggests that the antihypertensive regimens used in the LIFE study had comparable effects on arterial stiffness (LIFE study; NCT00338260)