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1.
  • Yang, Wen-Yi, et al. (author)
  • Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes
  • 2019
  • In: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 322:5, s. 409-420
  • Journal article (peer-reviewed)abstract
    • ImportanceBlood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. ObjectiveTo evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and ParticipantsLongitudinal population-based cohort study of 11135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). ExposuresBlood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and MeasuresMultivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). ResultsAmong 11135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P<.001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and RelevanceIn this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.
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  • Bodegard, J., et al. (author)
  • Possible angina detected by the WHO angina questionnaire in apparently healthy men with a normal exercise ECG: coronary heart disease or not? A 26 year follow up study
  • 2004
  • In: Heart. - 1468-201X. ; 90:6, s. 627-32
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To determine whether men with possible angina (from their responses to the World Health Organization angina questionnaire) but a normal exercise ECG differ in long term rates of coronary heart disease events from men with no symptoms of angina. DESIGN: During 1972-75, 2014 apparently healthy men aged 40-59 years underwent an examination programme including case history, clinical examination, exercise ECG to exhaustion, and various other tests. All men completed the WHO angina questionnaire. SUBJECTS: Of 2014 men, 68 had possible angina, 1831 had no symptoms of angina, and 115 were excluded because they had definite angina or pathological exercise ECGs. All 68+1831 had normal exercise ECGs and none developed chest pain during the exercise test. RESULTS: At 26 years, men with possible angina had a coronary heart disease mortality of 25.0% (17/68) v 13.8% (252/1831) among men with no symptoms of angina (p < 0.013). They also had a higher incidence of coronary artery bypass grafting (CABG) (p < 0.0004) and acute myocardial infarction (p < 0.026). The excess coronary heart disease mortality among men with possible angina only started after 15 years, whereas differences in CABG/acute myocardial infarction started early. Multivariate analysis including well recognised coronary heart disease risk factors showed that possible angina was an independent risk factor (relative risk 1.79, 95% confidence interval 1.26 to 2.10). CONCLUSIONS: Men with possible angina, even with a normal exercise test, have a greater risk of dying from coronary heart disease, having an acute myocardial infarct, or needing a CABG than age matched counterparts with no symptoms of angina.
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  • Bodegard, J., et al. (author)
  • Symptom-limited exercise testing, ST depressions and long-term coronary heart disease mortality in apparently healthy middle-aged men
  • 2004
  • In: Eur J Cardiovasc Prev Rehabil. - : Oxford University Press (OUP). - 1741-8267. ; 11:4, s. 320-7
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Previous studies have shown that ST depressions > or =1.0 mm during or post-exercise increase long-term risk of dying from coronary heart disease (CHD), the need for coronary artery bypass grafting (CABG) or the development of acute myocardial infarction (AMI) in healthy men. In the present prospective cohort study we investigate whether less marked ST depressions may influence CHD mortality, incidence of AMI, the need for a CABG or having a non-fatal stroke. METHODS: During 1972-75, 2014 men aged 40-59 years, free from somatic diseases and not using any drugs, underwent an examination programme including case history, clinical examination, various blood tests and a symptom-limited exercise ECG-test. ECG was registered during exercise and at 30 s, 1, 2, 3 and 5 min post-exercise. The possible prognostic impact of ST-changes of 0.50-0.99 mm and > or =1.00 mm compared with normal ST-segments were studied separately and combined. Horizontal, down-sloping and slowly up-sloping ST-segment patterns were combined. RESULTS: After adjustment for age, smoking, blood pressure, cholesterol, maximal heart rate, left ventricular hypertrophy and physical fitness ST depressions > or =0.50 mm--during and/or post-exercise--were associated with a 1.47-fold [95% confidence interval (CI) 1.10-1.95], and 1.54-fold (95% CI of 1.17-2.04) increased 26 years risk of CHD-mortality, respectively. The same ST-changes also increased 22 years risk of developing non-fatal AMI or needing CABG but not developing non-fatal stroke. CONCLUSIONS: Even an ST depression > or =0.50 mm during and/or after exercise increases the long-term risk of CHD-death, developing an AMI or needing CABG. No association was found between ST-changes and incidence of non-fatal strokes.
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  • Erikssen, G., et al. (author)
  • Exercise testing of healthy men in a new perspective: from diagnosis to prognosis
  • 2004
  • In: Eur Heart J. - 0195-668X. ; 25:11, s. 978-86
  • Journal article (peer-reviewed)abstract
    • AIM: It has recently been suggested that exercise testing may be more valuable prognostically than it is diagnostically in apparently healthy subjects. We wanted to compare the accuracy of CHD risk assessment based on classical risk factors with an assessment also based on multiple exercise test parameters. METHODS AND RESULTS: In 1972-75, 2014 apparently healthy men aged 40-60 had a symptom limited exercise test during a cardiovascular survey. Three hundred died from CHD during 26 years of follow-up. Compared to Cox regression models solely including classical risk factors (CRF), models also including multiple exercise test parameters (CRF+X) were clearly superior (P < 0.0001). Risk scores were computed based on the models. CRF and CRF+X risk scores often differed markedly; CRF+X scores were generally most reliable in both the high and low risk range. In smokers with cholesterol >6.5 mmol/l (n = 470), the CRF and CRF+X models identified 67 vs. 110 men at the highest CHD risk level according to European guidelines (34.2% vs. 38.2% CHD mortality). Three in five CRF+X-identified smokers with cholesterol >6.5 mmol/l had CHD mortality similar to the mean of all 2014 men. CONCLUSION: Integration of multiple exercise test parameters and conventional risk factors improved CHD risk assessment substantially--especially in smokers with high cholesterol.
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  • Bodegard, J, et al. (author)
  • Changes in body mass index following newly diagnosed type 2 diabetes and risk of cardiovascular mortality: A cohort study of 8486 primary-care patients
  • 2013
  • In: Diabetes & Metabolism. - : MASSON EDITEUR, 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE. - 1262-3636 .- 1878-1780. ; 39:4, s. 306-313
  • Journal article (peer-reviewed)abstract
    • Aims. - Elevated body mass index (BMI) is associated with an increased risk of type 2 diabetes and cardiovascular disease (CVD). This study explored the association between BMI changes in the first 18 months of newly diagnosed type 2 diabetes and the risk of long-term CVD mortality. less thanbrgreater than less thanbrgreater thanMethods. - A total of 8486 patients with newly diagnosed type 2 diabetes and no previous history of CVD or cancer were identified from 84 primary-care centres in Sweden. During the first year after diagnosis, patients were grouped according to BMI change: Increase, or andgt;= +1 BMI unit; unchanged, or between +1 and-1 BMI unit; and decrease, or andlt;=-1 BMI unit. Associations between BMI change and CVD mortality, defined as death from stroke, myocardial infarction or sudden death, were estimated using adjusted Cox proportional hazards models (NCT 01121315). less thanbrgreater than less thanbrgreater thanResults. - Baseline mean age was 60.0 years and mean BMI was 30.2 kg/m(2). Patients were followed for up to 9 years (median: 4.6 years). During the first 18 months, 53.4% had no change in their BMI, while 32.2% decreased and 14.4% increased. Compared with patients with unchanged BMI, those with an increased BMI had higher risks of CVD mortality (hazard ratio: 1.63, 95% CI: 1.11-2.39) and all-cause mortality (1.33, 1.01-1.76). BMI decreases had no association with these risks compared with unchanged BMI: 1.06 (0.76-1.48) and 1.06 (0.85-1.33), respectively. less thanbrgreater than less thanbrgreater thanConclusion. - Increased BMI within the first 18 months of type 2 diabetes diagnosis was associated with an increased long-term risk of CVD mortality. However, BMI decrease did not lower the long-term risk of mortality.
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  • Carlborg, A, et al. (author)
  • Characteristics of bipolar disorder patients treated with immediate- and extended-release quetiapine in a real clinical setting: a longitudinal, cohort study of 1761 patients
  • 2015
  • In: Therapeutic advances in psychopharmacology. - : SAGE Publications. - 2045-1253 .- 2045-1261. ; 5:1, s. 13-21
  • Journal article (peer-reviewed)abstract
    • The objective of this work was to study characteristics and clinical treatment patterns of bipolar disorder (BD) patients admitted to hospital and treated with quetiapine (immediate-release [IR] or extended-release [XR] formulations). Methods: BD patients admitted to hospital and prescribed quetiapine IR were followed by linking two Swedish nationwide registries; the hospitalization and drug dispense registries [ClinicalTrials.gov identifier: NCT01455961]. The study period was from 1 January 2008, to end of 31 December 2011. Data was primarily analysed using descriptive methods. Results: Quetiapine IR was used in 1761 patients of whom 1303 subsequently switched to XR (switch XR) and 458 remained on IR (continuous IR). At baseline, Switch XR patients were younger (−3.3 years), more frequently employed (+7.1%), had higher prevalence of single depressive episodes (+6.7%) and anxiety disorders (+5.8%), lower mean daily IR dose (−19.3%) and fewer medications for somatic disorders (−7.5%) than continuous IR patients. During follow up, the number of concomitant psychiatric medications was lower in switch XR patients (−6%) and higher in continuous IR patients (+6%). Mean daily quetiapine dose was 21% higher in switch XR versus continuous IR patients. Prescriptions of lower quetiapine dosages calculated below 50 mg per day in the XR switch and IR continuous groups were seen in 8% versus 10% of the patients, respectively. Conclusions: Differential use of quetiapine XR and IR in bipolar disorder patients with different and important characteristics was demonstrated. Patients who were switched to quetiapine XR had a higher psychiatric disease burden, were younger and had a higher degree of employment. These differences demonstrate the heterogeneity among bipolar disorder patients and indicate the need in clinical practice for individualized treatment to reduce the risk for both patient and society related losses.
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  • Gu, Yu-Mei, et al. (author)
  • Outcome-Driven Thresholds for Ambulatory Pulse Pressure in 9938 Participants Recruited From 11 Populations
  • 2014
  • In: Hypertension. - 0194-911X .- 1524-4563. ; 63:2, s. 229-237
  • Journal article (peer-reviewed)abstract
    • Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24-hour ambulatory PP, we analyzed 9938 participants randomly recruited from 11 populations (47.3% women). After age stratification (<60 versus >= 60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (IIRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68 853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top PP tenth (mean, 60.6 mm Hg). Using stepwise increasing PP levels, the lower boundary of the 95% confidence interval of the successive thresholds did not cross unity. Among 3910 older participants (39 923 person-years), risk increased (P <= 0.028) in the top PP tenth (mean, 76.1 mm Hg). HRs were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69, and 1.40 for all cardiovascular, cardiac, and cerebrovascular events. The lower boundary of the 95% confidence interval of the HRs associated with stepwise increasing PP levels crossed unity at 64 mm Hg. While accounting for all covariables, the top tenth of PP contributed less than 0.3% (generalized R-2 statistic) to the overall risk among the elderly. Thus, in randomly recruited people, ambulatory PP does not add to risk stratification below age 60; in the elderly, PP is a weak risk factor with levels below 64 mm Hg probably being innocuous.
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  • Hasvold, L. P., et al. (author)
  • Diabetes and CVD risk during angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment in hypertension : a study of 15 990 patients
  • 2014
  • In: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 28:11, s. 663-669
  • Journal article (peer-reviewed)abstract
    • Differences in clinical effectiveness between angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in the primary treatment of hypertension are unknown. The aim of this retrospective cohort study was to assess the prevention of type 2 diabetes and cardiovascular disease (CVD) in patients treated with ARBs or ACEis. Patients initiated on enalapril or candesartan treatment in 71 Swedish primary care centers between 1999 and 2007 were included. Medical records data were extracted and linked with nationwide hospital discharge and cause of death registers. The 11 725 patients initiated on enalapril and 4265 on candesartan had similar baseline characteristics. During a mean follow-up of 1.84 years, 36 482 patient-years, the risk of new diabetes onset was lower in the candesartan group (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.96, P = 0.01) compared with the enalapril group. No difference between the groups was observed in CVD risk (HR 0.99, 95% CI 0.87-1.13, P = 0.86). More patients discontinued treatment in the enalapril group (38.1%) vs the candesartan group (27.2%). In a clinical setting, patients initiated on candesartan treatment had a lower risk of new-onset type 2 diabetes and lower rates of drug discontinuation compared with patients initiated on enalapril. No differences in CVD risk were observed.
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  • Hedberg, Jakob, et al. (author)
  • Low-dose acetylsalicylic acid and gastrointestinal ulcers or bleeding - a cohort study of the effects of proton pump inhibitor use patterns
  • 2013
  • In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 274:4, s. 371-380
  • Journal article (peer-reviewed)abstract
    • Objective The aim of this study was to investigate the associations between proton pump inhibitor (PPI) usage patterns and risk of severe gastrointestinal events in patients treated with low-dose acetylsalicylic acid (LDA). Design and setting A nationwide cohort study in Sweden. Patients All Swedish residents 40years of age, without cancer and receiving LDA treatment (80% adherence for 365days between 2005 and 2009) were identified in the Swedish Prescription Register. Continuous PPI use was defined as >60 of 90days covered by daily PPI doses and further divided into high (80%) or moderate (<80) adherence. All other PPI use was defined as intermittent use. Main outcome measures The risk of a combined end-point of gastrointestinal ulcer or bleeding was analysed using Cox proportional hazard models. We also investigated risk of >45days of LDA treatment interruption. Results During a median follow-up of 2.5years, 7880 of 648807 (1.2%) LDA-treated patients experienced gastrointestinal events. In multivariable-adjusted models, both intermittent-PPI and no-PPI use were associated with increased risk of gastrointestinal ulcers or bleeding compared with continuous PPI use with a high level of adherence [hazard ratio (HR) 1.83 (95% CI 1.66-2.02) and 1.14 (95% CI 1.05-1.23), respectively]. Amongst continuous PPI users, moderate adherence also increased the risk of gastrointestinal ulcers or bleeding [HR 1.22 (95% CI 1.07-1.40)]. The risk of LDA treatment interruption was higher with intermittent PPI use [HR 1.16 (95% CI 1.14-1.19)] than continuous PPI use with high adherence. Conclusions In this large cohort of LDA users, intermittent PPI use was associated with higher risk of gastrointestinal ulcers or bleeding and interrupted LDA treatment, compared with continuous PPI use.
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  • Henriksson, M., et al. (author)
  • Health-care costs of losartan and candesartan in the primary treatment of hypertension
  • 2011
  • In: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 25:2, s. 130-136
  • Journal article (peer-reviewed)abstract
    • A recent study of two widely used angiotensin receptor blockers reported a reduced risk of cardiovascular events (-14.4%) when using candesartan compared with losartan in the primary treatment of hypertension. In addition to clinical benefits, costs associated with treatment strategies must be considered when allocating scarce health-care resources. The aim of this study was to assess resource use and costs of losartan and candesartan in hypertensive patients. Resource use (drugs, outpatient contacts, hospitalizations and laboratory tests) associated with losartan and candesartan treatment was estimated in 14 100 patients in a real-life clinical setting. We electronically extracted patient data from primary care records and mandatory Swedish national registers for death and hospitalization. Patients treated with losartan had more outpatient contacts (+15.6%), laboratory tests (+13.8%) and hospitalizations (+13.8%) compared with the candesartan group. During a maximum observation time of 9 years, the mean total costs per patient were 10 369 Swedish kronor (95% confidence interval: 3109-17 629) higher in the losartan group. In conclusion, prescribing candesartan for the primary treatment of hypertension results in lower long-term health-care costs compared with losartan.
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  • Kjeldsen, S. E., et al. (author)
  • Effects of losartan vs candesartan in reducing cardiovascular events in the primary treatment of hypertension
  • 2010
  • In: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 24:4, s. 263-273
  • Journal article (peer-reviewed)abstract
    • Although angiotensin receptor blockers have different receptor binding properties no comparative studies with cardiovascular disease (CVD) end points have been performed within this class of drugs. The aim of this study was to test the hypothesis that there are blood pressure independent CVD-risk differences between losartan and candesartan treatment in patients with hypertension without known CVD. Seventy-two primary care centres in Sweden were screened for patients who had been prescribed losartan or candesartan between the years 1999 and 2007. Among the 24 943 eligible patients, 14 100 patients were diagnosed with hypertension and prescribed losartan (n = 6771) or candesartan (n = 7329). Patients were linked to Swedish national hospitalizations and death cause register. There was no difference in blood pressure reduction when comparing the losartan and candesartan groups during follow-up. Compared with the losartan group, the candesartan group had a lower adjusted hazard ratio for total CVD (0.86, 95% confidence interval (CI) 0.77-0.96, P = 0.0062), heart failure (0.64, 95% CI 0.50-0.82, P = 0.0004), cardiac arrhythmias (0.80, 95% CI 0.65-0.92, P = 0.0330), and peripheral artery disease (0.61, 95% CI 0.41-0.91, P = 0.0140). No difference in blood pressure reduction was observed suggesting that other mechanisms related to different pharmacological properties of the drugs may explain the divergent clinical outcomes.
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