| 1. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(författare)
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Masked hypertension in a middle-aged population and its relation to manifestations of vascular disease
- 2023
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Ingår i: Journal of Hypertension. - : Wolters Kluwer. - 0263-6352 .- 1473-5598. ; 41:7, s. 1084-1091
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Tidskriftsartikel (refereegranskat)abstract
- Background: Masked hypertension is associated with cardiovascular disease (CVD). However, previous large studies have not used the same device to measure office and home blood pressure (BP) and adhered to current home BP measurement recommendations of the European Society of Hypertension. We aimed to characterize masked hypertension and explore its relation to manifestations of CVD.Methods: A randomly selected cohort of 5057 participants aged 50–64 years from the Swedish CardioPulmonary BioImage Study (SCAPIS) was evaluated with office and home BP using the semi-automatic Omron M10-IT oscillometric device. Additional analyses included pulse wave velocity (PWV) and coronary artery calcium score (CACS).Results: Of participants, 4122 did not have current antihypertensive treatment, and were thus included in our analyses. Of these, 2634 (63.9%) had sustained normotension, and 172 (4.2%) had masked hypertension. Participants with masked hypertension vs. sustained normotension were more often men (66.9 vs. 46.2%, P < 0.001). Those with masked hypertension had higher mean PWV [9.3 (95% confidence interval, 95% CI 9.1–9.5) vs. 8.3 (95% CI 8.2–8.4) m/s, P < 0.001] and odds ratio for CACS at least 100 [1.65 (95% CI 1.02–2.68), P = 0.040]. These associations were similar in a posthoc analysis of masked hypertension and sustained normotension, matched for age, sex and systolic office BP.Conclusion: Masked hypertension was associated with markers of CVD. This suggests that home BP is a better predictor of risk, even when the recordings are performed with the same measurement device, in a population-based setting with randomized recruitment.
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| 2. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(författare)
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P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy
- 2024
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.Results: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.Conclusion: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.
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| 3. |
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| 4. |
- Ahluwalia, Tarunveer S, et al.
(författare)
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Uromodulin gene variant is associated with type 2 diabetic nephropathy.
- 2011
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Ingår i: Journal of Hypertension. - 1473-5598. ; 29, s. 1731-1734
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: About 35% of individuals with type 2 diabetes develop persistent albuminuria, lose renal function, and are at increased risk for microvascular complications like diabetic nephropathy. Recent genome-wide association studies have identified the uromodulin locus (UMOD), encoding the most common protein in human urine to be associated with hypertension and also with chronic kidney disease (CKD). In the present study we examined the association of the common variant of the uromodulin (UMOD) gene with type 2 diabetic nephropathy and kidney function. METHODS: UMOD variant rs13333226 was genotyped in a case-control material including 4888 unrelated type 2 diabetic individuals (n = 880 with and n = 4008 without nephropathy) from Sweden (Scania Diabetes Registry) using the ABI Real time TaqMan allelic discrimination assay. RESULTS: The G allele of rs13333226 was associated with a decreased risk of nephropathy [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69-0.91, P = 0.001] after correction for confounding factors like age, sex, body mass index (BMI), blood pressure, kidney function, smoking and duration of diabetes. The same allele was also associated with a better kidney function [estimated glomerular filtration rate (eGFR), β = 0.117, P < 0.0001] and lower systolic blood pressure (β = -0.048, P = 0.013) in the overall study cohort. CONCLUSION/INTERPRETATION: The present study highlights that the common variant of the UMOD gene is protective against diabetic nephropathy susceptibility and also affects kidney function and blood pressure in patients with type 2 diabetes. However, the association with diabetic nephropathy was independent of blood pressure and kidney function.
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| 5. |
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| 6. |
- Alhadad, Alaa, et al.
(författare)
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Renal angioplasty causes a rapid transient increase in inflammatory biomarkers, but reduced levels of interleukin-6 and endothelin-1 1 month after intervention.
- 2007
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Ingår i: Journal of hypertension. - 0263-6352 .- 1473-5598. ; 25:9, s. 1907-14
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine prospectively whether inflammatory biomarkers and endothelin (ET)-1 are increased in patients with renal artery stenosis (RAS), and to investigate how treatment with percutaneous transluminal renal angioplasty (PTRA) affects these variables during the first month after intervention. METHODS: One hundred patients with suspected RAS undergoing renal angiography were included. PTRA was performed if the trans-stenotic mean arterial pressure gradient was>or=10 mmHg. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha), neopterin, CD40 ligand (CD40L) and endothelin-1 (ET-1) were measured before, and 1 day and 1 month after PTRA (n=61) or diagnostic angiography only (n=39). RESULTS: At baseline there were no significant differences in inflammatory biomarkers or ET-1 levels between patients subsequently undergoing PTRA or angiography only. After angiography, IL-6 and hs-CRP had increased in both groups compared to baseline (P<0.001). At this time point hs-CRP (10.90+/-1.48 versus 6.37+/-1.61 mg/l; P<0.05) and IL-6 (13.70+/-0.94 versus 13.00+/-0.17 pg/ml; P<0.01) were higher in the PTRA group than in patients subjected to angiography only. One month after PTRA, systolic blood pressure and levels of IL-6 and ET-1 were lower than before intervention (P<0.05), whereas CD40L had increased compared to baseline (P<0.01). CONCLUSION: In patients with RAS, PTRA triggers rapid transient increases in hs-CRP and IL-6; however, 1 month after PTRA, both IL-6 and ET-1 had decreased compared to before intervention, indicating beneficial effects of PTRA on inflammation and the endothelin system.
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| 7. |
- Andersen, Kasper, et al.
(författare)
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Muscle Morphology And Risk Of Cardiovascular Disease
- 2010
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Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352 .- 1473-5598. ; 28, s. E353-E353
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Andersson, Tobias, 1976, et al.
(författare)
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Country of birth and mortality risk in hypertension with and without diabetes: the Swedish primary care cardiovascular database.
- 2021
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Ingår i: Journal of hypertension. - 1473-5598. ; 39:6, s. 1155-1162
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Tidskriftsartikel (refereegranskat)abstract
- Hypertension and diabetes are common and are both associated with high cardiovascular morbidity and mortality. We aimed to investigate associations between mortality risk and country of birth among hypertensive individuals in primary care with and without concomitant diabetes, which has not been studied previously. In addition, we aimed to study the corresponding risks of myocardial infarction and ischemic stroke.This observational cohort study of 62557 individuals with hypertension diagnosed 2001-2008 in the Swedish Primary Care Cardiovascular Database assessed mortality by the Swedish Cause of Death Register, and myocardial infarction and ischemic stroke by the National Patient Register. Cox regression models were used to estimate study outcome hazard ratios by country of birth and time updated diabetes status, with adjustments for multiple confounders.During follow-up time without diabetes using Swedish-born as reference, adjusted mortality hazard ratios per country of birth category were Finland: 1.26 (95% confidence interval 1.15-1.38), high-income European countries: 0.84 (0.74-0.95), low-income European countries: 0.84 (0.71-1.00) and non-European countries: 0.65 (0.56-0.76). The corresponding adjusted mortality hazard ratios during follow-up time with diabetes were high-income European countries: 0.78 (0.63-0.98), low-income European countries: 0.74 (0.57-0.96) and non-European countries: 0.56 (0.44-0.71). During follow-up without diabetes, the corresponding adjusted hazard ratio of myocardial infarction was increased for Finland: 1.16 (1.01-1.34), whereas the results for ischemic stroke were inconclusive.In Sweden, hypertensive immigrants (with the exception for Finnish-born) with and without diabetes have a mortality advantage, as compared to Swedish-born.
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| 9. |
- Andersson, Ulrika, et al.
(författare)
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PERson-centredness in Hypertension management using Information Technology: a randomized controlled trial in primary care
- 2023
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Ingår i: Journal of hypertension. - : LIPPINCOTT WILLIAMS & WILKINS. - 1473-5598 .- 0263-6352. ; 41:2, s. 246-253
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To increase the proportion of individuals with hypertension obtaining a blood pressure (BP) of less than 140/90mmHg by improving the management of hypertension in daily life from a person-centred perspective. METHODS: In this unblinded randomized controlled trial, we tested an interactive web-based self-management system for hypertension. A total of 949 patients with hypertension from 31 primary healthcare centres (PHCCs) in Sweden were randomized 1:1 to either the intervention or usual care group. The intervention included daily measurement - via the participant's mobile phone - of BP and pulse and reports of well being, symptoms, lifestyle, medication intake and side effects for eight consecutive weeks. It also included reminders and optional motivational messages. The primary outcome was the proportion of participants obtaining BP of less than 140/90mmHg at 8 weeks and 12months. Significance was tested by Pearson's chi 2 -test. RESULTS: A total of 862 patients completed the trial, 442 in the intervention group and 420 in the control group. The primary outcome (BP <140/90mmHg) at 8 weeks was achieved by 48.8% in the intervention group and 39.9% in the control group ( P =0.006). At 12months, 47.1% (intervention) and 41.0% (control group) had a BP less than 140/90mmHg ( P =0.071). CONCLUSION: The proportion of participants with a controlled BP of less than 140/90mmHg increased after using the interactive system for self-management of hypertension for 8 weeks compared with usual care. Although the trend continued, there was no significant difference after 12months. The results indicate that the effect of the intervention is significant, but the long-term effect is uncertain. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (NCT03554382).
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| 10. |
- Andersson, Ulrika, et al.
(författare)
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PERSON-CENTREDNESS IN HYPERTENSION MANAGEMENT USING INFORMATION TECHNOLOGY (PERHIT) : A RANDOMISED CONTROLLED TRIAL IN PRIMARY HEALTH CARE
- 2022
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Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 1473-5598 .- 0263-6352. ; 40, s. 197-197
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- OBJECTIVE: Few studies address results from use of new technology and patient participation in hypertension management. The PERHIT Study is a multicentre randomised controlled trial with the aim to evaluate the effects of a person-centred approach using a web-based, interactive self-management system through the patient´s own mobile phone on blood-pressure and well-being. Primary aim is the degree of achieved blood pressure (BP) control after eight weeks and one year. In addition, person-centeredness, usefulness, daily life activities in relation to BP values, awareness of risk and health care costs are studied. DESIGN AND METHOD: The PERHIT study was performed in four regions in southern Sweden. Following inclusion, more than 900 patients from 31 primary health care centres were randomised to two groups. In the intervention group (INT), patients were provided with a web-based self-management support system including a home-BP monitor. For eight consecutive weeks, they measured BP and performed self-reports regarding well-being, symptoms, lifestyle, medication intake and side effects every evening via their mobile phone. They could also receive motivational messages and reminders throughout the intervention period. Both patients and professionals had access to graphic feedback of reported values through a secure web portal. Patients in the control (CON) group received standard treatment as usual. RESULTS: The primary outcome (BP < 140/90 mmHg) was achieved by 48.5% and 47.1% in the INT, and by 40.4% and 40.9% in the CON group after 8 weeks (p = 0.016) and 12 months (p = 0.067), respectively. Both patients and professionals experienced the system as a useful resource for communication regarding BP and lifestyle. They described that it could be used to support a constructive and person-centred partnership between patients and professionals. CONCLUSIONS: Blood pressure control was significantly better after eight weeks, but not after one year, following an intervention based on use of mobile phones, feedback and interaction between patients and primary care professionals compared to standard care. The system can be a tool toward a new way of working and help patients reach a controlled BP and play a role in a more person-centred and individually adapted hypertension management.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Bager, Johan-Emil, et al.
(författare)
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Blood pressure levels and risk of haemorrhagic stroke in patients with atrial fibrillation and oral anticoagulants: results from The Swedish Primary Care Cardiovascular Database of Skaraborg.
- 2021
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Ingår i: Journal of hypertension. - 1473-5598. ; 39:8, s. 1670-1677
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Tidskriftsartikel (refereegranskat)abstract
- To assess the risk of haemorrhagic stroke at different baseline SBP levels in a primary care population with hypertension, atrial fibrillation and newly initiated oral anticoagulants (OACs).We identified 3972 patients with hypertension, atrial fibrillation and newly initiated OAC in The Swedish Primary Care Cardiovascular Database of Skaraborg. Patients were followed from 1 January 2006 until a first event of haemorrhagic stroke, death, cessation of OAC or 31 December 2016. We analysed the association between continuous SBP and haemorrhagic stroke with a multivariable Cox regression model and plotted the hazard ratio as a function of SBP with a restricted cubic spline with 130mmHg as reference.There were 40 cases of haemorrhagic stroke during follow-up. Baseline SBP in the 145-180mmHg range was associated with a more than doubled risk of haemorrhagic stroke, compared with a SBP of 130mmHg.In this cohort of primary care patients with hypertension and atrial fibrillation, we found that baseline SBP in the 145-180mmHg range, prior to initiation of OAC, was associated with a more than doubled risk of haemorrhagic stroke, as compared with an SBP of 130mmHg. This suggests that lowering SBP to below 145mmHg, prior to initiation of OAC, may decrease the risk of haemorrhagic stroke in patients with hypertension and atrial fibrillation.
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| 15. |
- Bager, Johan-Emil, et al.
(författare)
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Treatment of hypertension in old patients without previous cardiovascular disease.
- 2019
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Ingår i: Journal of hypertension. - 1473-5598. ; 37:11, s. 2269-2279
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the risk of cardiovascular disease (CVD) - nonfatal acute myocardial infarction (AMI) or stroke - at blood pressure levels that meet current recommendations with risk at lower levels, particularly in older patients.We identified patients with hypertension aged 40-90 years from a primary care register. Patients with a history of cancer, diabetes mellitus or CVD were excluded. Patients were divided into age groups (40-75 and 76-90), and four groups of SBP 110-129, 130-139 (reference), 140-149 and ≥150mmHg. We used the Kaplan-Meier estimator to study incidence of AMI, stroke and a composite of the two. Cox proportional-hazards regression was used to estimate hazard ratios for outcomes.We included 31704 patients: 26663 were 40-75 years old and 5041 were 76-90 years old. Mean follow-up was 2 years. Although no significant differences in risk of any outcome were found in the younger group, low blood pressure was associated with the lowest risk in the older group. Older patients in the 110-129mmHg group had a lower incidence of CVD (15.9/1000 vs. 25.3/1000 person-years) than the reference group. After adjustment for covariates, the hazard ratio of CVD in older patients in the 110-129mmHg group compared with the reference group was 0.60 (95% confidence interval 0.40-0.92).Blood pressure levels lower than those currently recommended are not harmful among older patients. The association between lower SBP and lesser risk of CVD may instead suggest a beneficial effect of lower SBP.
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| 16. |
- Bang, Casper N., et al.
(författare)
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Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients : the Losartan Intervention For Endpoint reduction in hypertension study
- 2013
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 31:10, s. 2060-2068
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Tidskriftsartikel (refereegranskat)abstract
- Background:Left ventricular hypertrophy [LVH, high left ventricular mass (LVM)] is traditionally classified as concentric or eccentric based on left ventricular relative wall thickness. We evaluated left ventricular systolic function in a new four-group LVH classification based on left ventricular dilatation [high left ventricular end-diastolic volume (EDV) index and concentricity (LVM/EDV(2/3))] in hypertensive patients.Methods and results:Nine hundred thirty-nine participants in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy had measurable LVM at enrolment. Patients with LVH (LVM/body surface area 116g/m(2) in men and 96g/m(2) in women) were divided into four groups; eccentric nondilated' (normal LVM/EDV and EDV), eccentric dilated' (increased EDV, normal LVM/EDV), concentric nondilated' (increased LVM/EDV with normal EDV), and concentric dilated' (increased LVM/EDV and EDV) and compared to patients with normal LVM. At baseline, 12% had eccentric nondilated, 20% eccentric dilated, 29% concentric nondilated, and 14% concentric dilated LVH, with normal LVM in 25%. Compared with the concentric nondilated LVH group, those with concentric dilated LVH had significantly lower pulse pressure/stroke index and ejection fraction; higher LVM index, stroke volume, cardiac output, left ventricular midwall shortening, left atrial volume and isovolumic relaxation time; and more had segmental wall motion abnormalities (all P<0.05). Similar differences existed between patients with eccentric dilated and those with eccentric nondilated LVH (all P<0.05). Compared with patients with normal LVM, the eccentric nondilated had higher LV stroke volume, pulse pressure/stroke index, Cornell voltage product and SBP, and lower heart rate and fewer were African-American (all P<0.05).Conclusion:The new four-group classification of LVH identifies dilated subgroups with reduced left ventricular function among patients currently classified with eccentric or concentric LVH.
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| 17. |
- Beijer, Kristina, et al.
(författare)
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Interaction between physical activity and television time on blood pressure level : cross-sectional data from 45000 individuals
- 2018
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 36:5, s. 1041-1050
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:The aim was to investigate if there is an interaction between sitting time and leisure time physical activity on blood pressure and if there are age differences and sex differences in this respect.Methods:Linear regression analysis on cross-sectional data was performed in more than 45000 men and women from two Swedish cohort studies, EpiHealth (45-75 years) and LifeGene (18-45 years). Self-reported leisure time physical activity was given in five levels from low (level 1) to vigorous physical activity (level 5) and television time was used as a proxy measure of sitting time.Results:High physical activity was associated with lower DBP (P=0.001), but not SBP. Active middle-aged men had lower DBP (-1.1mmHg; 95% CI -1.7 to -0.4) compared with inactive participants. Prolonged television time was associated with higher SBP (P<0.001) and DBP (P=0.011) in both sexes and in most age groups. Watching 3h instead of 1h television per day was associated with higher SBP in middle-aged women (SBP: 1.1mmHg; 95% CI 0.7-1.4) and men (SBP: 1.2mmHg; 95% CI 0.8-1.6). Only in young men, a high physical activity (level 4 instead of level 1) could compensate for a prolonged television time (3h per day) in terms of DBP.Conclusion:Prolonged television time was associated with higher SBP and DBP in both sexes and at most ages, whereas an increased physical activity was mainly associated with a lower DBP. Only in young men, a high physical activity could compensate for prolonged television time regarding DBP.
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| 18. |
- Bejan-Angoulvant, Theodora, et al.
(författare)
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Treatment of hypertension in patients 80 years and older : the lower the better? A meta-analysis of randomized controlled trials.
- 2010
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 28:7, s. 1366-1372
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Tidskriftsartikel (refereegranskat)abstract
- Background: Results of randomized controlled trials are consistent in showing reduced rates of stroke, heart failure and cardiovascular events in very old patients treated with antihypertensive drugs. However, inconsistencies exist with regard to the effect of these drugs on total mortality. Methods: We performed a meta-analysis of available data on hypertensive patients 80 years and older by selecting total mortality as the main outcome. Secondary outcomes were coronary events, stroke, cardiovascular events, heart failure and cause-specific mortality. The common relative risk (RR) of active treatment versus placebo or no treatment was assessed using a random-effect model. Linear meta-regression was performed to explore the relationship between intensity of antihypertensive therapy and blood pressure (BP) reduction and the log-transformed value of total mortality odds ratios (ORs). Results: The overall RR for total mortality was 1.06 (95% confidence interval 0.89–1.25), with significant heterogeneity between hypertension in the very elderly trial (HYVET) and the other trials. This heterogeneity was not explained by differences in the follow-up duration between trials. The meta-regression suggested that a reduction in mortality was achieved in trials with the least BP reductions and the lowest intensity of therapy. Antihypertensive therapy significantly reduced (P < 0.001) the risk of stroke (35%), cardiovascular events (27%) and heart failure (50%). Cause-specific mortality was not different between treated and untreated patients. Conclusion: Treating hypertension in very old patients reduces stroke and heart failure with no effect on total mortality. The most reasonable strategy is the one associated with significant mortality reduction; thiazides as first-line drugs with a maximum of two drugs.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Bengtsson Boström, Kristina, et al.
(författare)
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Interaction between the angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea as a mechanism for hypertension
- 2007
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Ingår i: J Hypertens. - 0263-6352. ; 25:4, s. 779-783
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Obstructive sleep apnoea (OSA) confers a risk of hypertension and cardiovascular complications. Both the renin-angiotensin-aldosterone system and OSA are important determinants of blood pressure, but it is not fully known how they interact. The aim of this study was to explore the interaction between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and OSA in the association with hypertension. DESIGN: A community-based, case-control design with hypertensive patients in primary care (n = 157) and normotensive population controls (n = 181). METHODS: All subjects underwent ambulatory polysomnography during one night. OSA was defined by a minimum of 10 apnoea/hypopnoea events per hour. Office blood pressure was measured and hypertension status was assessed. The genotypes were determined using polymerase chain reaction. RESULTS: An interaction analysis including sex, ACE I/D polymorphism (DD and ID versus II), and OSA identified a significant interaction between OSA and the ACE I/D polymorphism: odds ratio (OR) 6.3, 95% confidence interval (CI) 1.8-22.5, P = 0.004 as well as between OSA and sex: OR 3.3, 95% CI 1.1-9.6, P = 0.033. OSA was significantly associated with hypertension in men but not in women. CONCLUSION: The interaction between the ACE gene I/D polymorphism and OSA appears to be an important mechanism in the development of hypertension, particularly in men.
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| 23. |
- Bengtsson Boström, Kristina, et al.
(författare)
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Polymorphism in the angiotensin converting enzyme but not in the angiotensinogen gene is associated with hypertension and type 2 diabetes: the Skaraborg Hypertension and diabetes project
- 1999
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Ingår i: Journal of Hypertension. - 1473-5598. ; 17:11, s. 1569-1575
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the association between polymorphisms in the angiotensin converting enzyme (ACE) gene and angiotensinogen (AGT) gene and hypertension and/or type 2 diabetes in a community population. PATIENTS AND METHODS: The insertion (I)/deletion (D) polymorphism of the ACE gene and the M235T polymorphism of the AGT gene were genotyped in 773 nondiabetic individuals with hypertension, 193 normotensive patients with type 2 diabetes, 243 patients with type 2 diabetes and hypertension, and in 820 normotensive control individuals identified in a community-based study. RESULTS: The DD genotype was associated with hypertension in individuals less than 70 years [odds ratio (OR) = 1.54, confidence interval (CI) = 1.09-2.18] and remained so when patients with type 2 diabetes were excluded from the analysis (OR = 1.45, CI = 1.01-2.09). The strongest association was with the combination of type 2 diabetes and hypertension (OR = 2.19, CI = 1.09-4.38). There was no association with type 2 diabetes without hypertension. No association was observed between the M235T variant or the 3'-microsatellite polymorphism of the AGT gene and hypertension. CONCLUSION: The D-allele of the ACE gene ID polymorphism increases susceptibility to hypertension, particularly when associated with type 2 diabetes. No association was observed between the M235T variant or 3'-microsatellite polymorphism of the AGT gene and hypertension.
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| 24. |
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| 25. |
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| 26. |
- Bokrantz, Tove, et al.
(författare)
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7b.10: Thiazide Diuretics and Fracture-Risk among Hypertensive Patients. Results from the Swedish Primary Care Cardiovascular Database (Spccd)
- 2015
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Ingår i: Journal of hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352 .- 1473-5598. ; 33 Suppl 1
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- OBJECTIVE: To investigate whether treatment with thiazide diuretics reduces the risk of osteoporotic fractures in hypertensive patients in primary health care. Further we aimed to examine the impact of duration of thiazide use, the consequences of discontinuation of use and effect-modifications by gender. DESIGN AND METHOD: This retrospective cohort study includes 60 893 individuals, diagnosed with hypertension during 2001-2008 included in the Swedish Primary Care Cardiovascular Database. All patients were followed from a fixed baseline (1 Jan 2006, or the date the patient received their first diagnosis of hypertension if that date came later) until they had an incident osteoporotic fracture, died, or reached the end of the study at 31 Dec 2012, whichever came first. Patients exposed to thiazide diuretics (dispensed drugs recorded through the Prescribed Drug Register) were compared with hypertensive patients never exposed to thiazides. RESULTS: During follow up 2421 osteoporotic fractures occurred. Current use of thiazide diuretics was found to be associated with significantly reduced risk of osteoporotic fractures (adjusted hazard ratios 0.88; 95% CI 0.81-0.97) independent of blood pressure level. In addition, risk appeared to decline with longer duration of use. In contrast, discontinuation of dispensed prescriptions of thiazides was associated with increased risk of osteoporotic fractures (HR 1.17; 95% CI 1.04-1.31).However, a trend towards attenuation of the increased risk with longer duration past treatment period was seen. When analyzing men and women separately similar results were seen, for both genders, although only statistically significant for men. CONCLUSIONS: In this large retrospective cohort study of hypertensive men and women from Sweden, we could identity a protective effect on osteoporotic fractures among current users of thiazide diuretic drugs independent of blood pressure level. However, the risk of fracture was found to be increased in patients shortly after discontinuation of treatment compared to patients never prescribed thiazide diuretic drugs. The reason for an augmented outcome on osteoporotic fractures among patients with former thiazide diuretic therapy needs to be further elucidated.
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| 27. |
- Bokrantz, Tove, et al.
(författare)
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Antihypertensive drug classes and the risk of hip fracture: results from the Swedish primary care cardiovascular database.
- 2020
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Ingår i: Journal of hypertension. - 1473-5598. ; 38:1, s. 167-175
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Tidskriftsartikel (refereegranskat)abstract
- Hypertension and fractures related to osteoporosis are major public health problems that often coexist. This study examined the associations between exposure to different antihypertensive drug classes and the risk of hip fracture in hypertensive patients.We included 59246 individuals, 50 years and older, diagnosed with hypertension during 2001-2008 in the Swedish Primary Care Cardiovascular Database. Patients were followed from 1 January 2006 (or the date of diagnosis of hypertension) until they had their first hip fracture, died, or reached the end of the study on 31 December 2012. Cox proportional hazards models were used to calculate the risk of hip fracture across types of antihypertensive medications, adjusted for age, sex, comorbidity, medications, and socioeconomic factors.In total, 2593 hip fractures occurred. Compared to nonusers, current use of bendroflumethiazide or hydrochlorothiazide was associated with a reduced risk of hip fracture (hazard ratio 0.86; 95% CI 0.75-0.98 and hazard ratio 0.84; 95% CI 0.74-0.96, respectively), as was use of fixed drug combinations containing a thiazide (hazard ratio 0.69; 95% CI 0.57-0.83). Current use of loop diuretics was associated with an increased risk of hip fracture (hazard ratio 1.23; 95% CI 1.11-1.35). No significant associations were found between the risk of hip fracture and current exposure to beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone-receptor blockers or calcium channel blockers.In this large observational study of hypertensive patients, the risk of hip fracture differed across users of different antihypertensive drugs, results that could have practical implications when choosing antihypertensive drug therapy.
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| 28. |
- Bokrantz, Tove, et al.
(författare)
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Reply.
- 2017
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Ingår i: Journal of hypertension. - 1473-5598. ; 35:3, s. 646-647
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 29. |
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| 30. |
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| 31. |
- Borghi, Claudio, et al.
(författare)
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The association between blood pressure and lipid levels in Europe : European study on cardiovascular risk prevention and management in usual daily practice
- 2016
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 34:11, s. 2155-2163
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:Several studies have suggested a positive association between serum lipid levels and blood pressure (BP). This study investigated this association in a large population from 12 European countries.Methods:Data were taken from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (ClinicalTrials.gov identifier: NCT00882336). Associations between BP and lipid levels in patients free from cardiovascular disease and with at least one major cardiovascular disease risk factor (N=7641) were assessed using linear regression analyses.Results:Overall, 72.8 and 64.8% of patients had hypertension and dyslipidaemia, respectively; 47.0% had both conditions. Regression coefficients (95% confidence interval) for the associations of LDL cholesterol, non-HDL cholesterol, total cholesterol and apolipoprotein B levels with SBP, adjusted for age, sex and BMI, were 0.93mmHg/mmol per l (0.54-1.31), 1.07mmHg/mmol per l (0.73-1.40), 1.02mmHg/mmol per l (0.69-1.35) and 4.94mmHg/g per l (3.43-6.46), respectively. The corresponding values (95% confidence interval) for the associations with DBP were 0.96mmHg/mmol per l (0.73-1.19), 0.95mmHg/mmol per l (0.75-1.15), 0.87mmHg/mmol per l (0.67-1.07) and 4.33mmHg/g per l (3.42-5.23), respectively. Most of these associations remained significant whether patients were treated with statins or not.Conclusion:Small but statistically significant associations between lipid levels and BP were observed in a large, multinational European population. Further research is warranted to assess the causality of this association and its implications on the management of patients with both hypertension and dyslipidaemia.
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| 32. |
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| 33. |
- Brignole, Michele, et al.
(författare)
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Low-blood pressure phenotype underpins the tendency to reflex syncope
- 2021
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Ingår i: Journal of Hypertension. - 1473-5598. ; 39:7, s. 1319-1325
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We hypothesized that cardiovascular physiology differs in reflex syncope patients compared with the general population, predisposing such individuals to vasovagal reflex.METHODS: In this multicohort cross-sectional study, we compared aggregate data of resting SBP, DBP, pulse pressure (PP) and heart rate (HR), collected from six community-based cohort studies (64 968 observations) with those from six databases of reflex syncope patients (6516 observations), subdivided by age decades and sex.RESULTS: Overall, in male individuals with reflex syncope, SBP (-3.4 mmHg) and PP (-9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages above 60 years. In female individuals, PP (-6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with male individuals, SBP in female individuals exhibited slower increase until age 40 years, and then demonstrated steeper increase that continued throughout remaining life.CONCLUSION: The patients prone to reflex syncope demonstrate a different resting cardiovascular haemodynamic profile as compared with a general population, characterized by lower SBP and PP, reflecting reduced venous return and lower stroke volume, and a higher HR and DBP, suggesting the activation of compensatory mechanisms. Our data contribute to a better understanding why some individuals with similar demographic characteristics develop reflex syncope and others do not.VIDEO ABSTRACT: http://links.lww.com/HJH/B580.
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| 34. |
- Brunström, Mattias, et al.
(författare)
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Blood pressure treatment levels and choice of antihypertensive agent in people with diabetes mellitus : an overview of systematic reviews
- 2017
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 35, s. 435-462
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: Multiple systematic reviews address the effect of antihypertensive treatment in people with diabetes. Here, we summarize current systematic reviews concerning antihypertensive treatment effect at different blood pressure (BP) levels, and relative treatment effect of different antihypertensive agents.METHODS: We searched MEDLINE, BIOSIS, DARE and CDSR during years 2005-2016. Eligibility criteria, number of trials and participants, outcomes analysed, statistical methods used for data synthesis, and principal results were extracted for each review. Review quality was assessed using the assessment of multiple systematic reviews tool.RESULTS: We found four reviews concerning BP treatment level. These consistently showed that the effect of antihypertensive treatment on mortality, cardiovascular disease and coronary heart disease was attenuated at lower BP levels. If SBP was more than 140 mmHg, treatment reduced all-cause and cardiovascular mortality, cardiovascular disease, stroke, myocardial infarction and heart failure. If SBP was less than 140 mmHg, treatment increased the risk of cardiovascular death. We found eight reviews concerning choice of agent. We found no difference between angiotensin-converting enzyme inhibitors, angotensin receptor blockers, beta-blockers, calcium channel blockers and diuretics in preventing all-cause or cardiovascular mortality, combined cardiovascular disease, coronary heart disease and end-stage renal disease. Minor differences exist for stroke and heart failure. Data were limited on people with type 1 diabetes and very elderly patients with type 2 diabetes. None of the reviews concerning choice of agent included all relevant trials.CONCLUSION: The available evidence supports treatment in people with type 2 diabetes and SBP more than 140 mmHg, using any of the major antihypertensive drug classes.
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| 35. |
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| 36. |
- Brunström, Mattias, et al.
(författare)
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SPRINT in context : meta-analysis of trials with baseline normotension and low levels of previous cardiovascular disease
- 2018
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 36:5, s. 979-986
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Forskningsöversikt (refereegranskat)abstract
- Objective: To estimate the effect of antihypertensive treatment in trials with baseline normotension and low levels of previous cardiovascular disease. To test if the results from SPRINT are compatible with those from other trials, and test the impact of SPRINT results on overall effect estimates. Methods: Systematic review and meta-analysis of randomized controlled trials with at least 1000 patient-years of follow-up, comparing antihypertensive treatment versus placebo, or different blood pressure goals against each other. Trials with at least 50% previous cardiovascular disease were excluded. Results: Sixteen trials, including 66816 participants, were included in the meta-analyses. Mean baseline SBP was 138mmHg, and mean difference between treatment arms was 5.5mmHg. Antihypertensive treatment was associated with a neutral effect on all-cause mortality [relative risk 0.98, 95% confidence interval (CI) 0.92-1.05] and major cardiovascular events (0.97, 0.91-1.03). Results from SPRINT differed significantly from those of other trials (P=0.012 for all-cause mortality; P=0.016 for major cardiovascular events), but overall effect estimates were similar when SPRINT was excluded (1.01, 0.95-1.06 for all-cause mortality; 0.98, 0.93-1.03 for major cardiovascular events). Treatment was associated with reduced risk of secondary outcomes stroke (0.84, 0.71-1.00) and heart failure (0.88, 0.78-0.98), although heterogeneity was high in the stroke analysis (I-2=54%). Conclusion: SPRINT results are not representative for trials with baseline normotension and low levels of previous cardiovascular disease. Antihypertensive treatment does not protect against death or major cardiovascular events in this setting.
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| 37. |
- Brunström, Mattias, et al.
(författare)
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Standardization according to blood pressure lowering in meta-analyses of antihypertensive trials : comparison of three methodological approaches
- 2018
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 36:1, s. 4-15
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: Assess how standardization of relative risks (RRs) and standard errors (SEs), according to blood pressure differences within trials, affects heterogeneity, overall effect estimates and study weights in meta-analyses of antihypertensive treatment.METHOD: Data from a previous systematic review were used. Three sets of analyses were performed, using both random-effects and fixed-effects model for meta-analyses. First, we used raw data from the included trials. Second, we standardized RRs as if SBP was reduced by 10 mmHg in all trials. Third, we standardized both RRs and SEs.RESULTS: When RRs were standardized according to blood pressure lowering, heterogeneity between trials increased (I = 36 vs. 93% for mortality). This conferred large differences in treatment effect estimates using random-effects and fixed-effects model (RR 0.79, 95% confidence interval 0.70-0.89, respectively, 0.97, 0.94-0.99). When SEs were standardized, confidence intervals for individual trials widened, resulting in lower power to detect heterogeneity across trials. Study weights were dissociated from number of events in trials (P < 0.0001, R = 0.99 before standardization vs. P = 0.063, R = 0.05 after standardization). This induced a secondary shift in weight from trials with lower baseline SBP to trials with higher baseline SBP, resulting in exaggerated overall effect estimates.CONCLUSION: Standardization of RRs exaggerates differences between trials and makes meta-analyses highly sensitive to choice of statistical method. Standardization of SEs masks heterogeneity and results in biased effect estimates.
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| 38. |
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| 39. |
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| 40. |
- Burger, Ronelle, et al.
(författare)
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Use of simulated patients to assess hypertension case management at public healthcare facilities in South Africa
- 2020
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Ingår i: Journal of Hypertension. - 1473-5598. ; 38:2, s. 362-367
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Our study aims to evaluate hypertensive case management in South Africa's public health sector using simulated patients.METHOD: Our study describes interactions between hypertensive simulated patients and primary healthcare workers at 39 public sector healthcare facilities in two metropolitan centres in the Eastern and Western Cape Provinces of South Africa. Our analysis focus on 97 interactions where our eight simulated patients tested within range for stage 1 hypertension, that is with SBP 140-159 mmHg and/or DBP 90-99 mmHg. For this subset, we describe how healthcare workers communicated the outcome of the blood pressure test, and whether they follow government guidelines on risk assessment and lifestyle advice.RESULTS: Healthcare workers highlighted the risks associated with hypertension in one out of three cases and stressed the importance of regular monitoring of blood pressure in less than half of cases. Hypertensive patients received advice on all six lifestyle risk factors in 8% of cases. 39% of patients received no lifestyle advice at all. In one out of four cases, hypertensive patients left the facility without a hypertension diagnosis and with no prospect of a follow-up visit.CONCLUSION: Simulated patients can assess the quality of hypertension case management, yielding granular and comprehensive information that can help mobilize resources to improve care. The management of hypertension patients in South African public healthcare facilities is critically insufficient. Given that hypertension is responsible for a rising share of deaths in South Africa and many of these deaths are preventable, urgent intervention is needed.
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| 41. |
- Carlberg, Bo
(författare)
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Is lower really better? : Issue of the J curve hypothesis in hypertension
- 2016
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Ingår i: Journal of Hypertension. - : Wolters Kluwer. - 0263-6352 .- 1473-5598. ; 34, s. e196-
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Tidskriftsartikel (refereegranskat)abstract
- The J curve hypothesis propose that the relation between blood pressure and risk for cardiovascular events is non-linear. Instead of a decreased risk with lower blood pressure, the risk increases at lower blood pressures. This issue has been discussed for many years, and is still a hot topic. The debates have most often had its origin in the question about how far blood pressure should be lowered with antihypertensive drugs.One one hand, we know that many patients with hypertension is not treated to targets according to guidelines and that this contributes to the high risk for cardiovascular diseases in patients with hypertension. On the other hand, overtreatment could be one reason for the subobtimal effect of antihypertensive drugs on cardiovascular diseases.The issue about a J curve in the effect of antihypertensive drugs is complicated.The relation between blood pressure and cardiovascular risk is different for different cardiovascular outcomes. For example, the risk for intracerebral hemorrhage seem to increase steeper at higher blood pressure than for most other outcomes. On the other hand, the risk for abdominal aortic aneurysm increases only modestly with higher blood pressure. In addition, end stage renal disease and cognitive decline could have other relations between blood pressure and risk. Age, cardiovascular disease and diabetes have also been found to modify the relation between risk and outcome.Earlier this year, we published a meta-analysis of randomized controlled trials with antihypertensive drugs in patients with diabetes mellitus (ref). Included trials had to compare treatment with an antihypertensive drug against placebo, two antihypertensive agents against one or one blood pressure target against another target. The studies were stratified according to blood pressure at randomization (baseline blood pressure), mimicking the situation you as a clinician meet when you decide to recommend a patients additional antihypertensive therapy or not. We contacted authors to receive data from diabetic subgroups in large studies. Thus, we were able to include more studies than in previous systematic reviews in this field. All together, we included data from 49 randomized controlled trials, including 73 738 patients.The systematic review showed that the effect of antihypertensive drugs on cardiovascular outcomes is different at different blood pressure levels. For most outcomes, adding antihypertensive drugs were beneficial in patients with diabetes mellitus and high blood pressure. However, this benefit decreased with decreasing blood pressure. The risk for cardiovascular death increased when therapy was added in patents with diabetes and systolic blood pressure below 140 mmHg. The benefits of adding antihypertensive treatment at different blood pressure levels are summarized in the figure below.Thus, in patients with diabetes, the relations between treatment effect of antihypertensive drugs are different at different blood pressure levels. Treatment effects differ for different cardiovascular outcomes. These data question previous guidelines that recommend a systolic blood pressure target below 130 mmHg in patients with diabetes mellitus.In a very recent systematic review, we have reexamined the relation between randomization blood pressure and cardiovascular stratified for different baseline blood pressures. The meta-analyses include patients with and without diabetes, with and without previous cardiovascular disease etc. Altogether, 58 trials with 290 000 patients were included. The study shows that the effect of blood pressure lowering on cardiovascular outcomes is dependent on baseline systolic blood pressure but also differ between different subsets of patients. This study is under review and the results will be presented during the lecture.
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Carlström, Mattias, et al.
(författare)
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Angiogenesis inhibition causes hypertension and placental dysfunction in a rat model of preeclampsia
- 2009
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 27:4, s. 829-837
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Tidskriftsartikel (refereegranskat)abstract
- Background Preeclampsia is a serious pregnancy complication, accompanied by increased maternal and fetal morbidity. Different models have been used to study preeclampsia, but none of these display all the key features of the disease. Method We investigated the effects on maternal blood pressure and fetal outcome exerted by the angiogenesis inhibitor Suramin (1100 mg/kg i.p.) during early placentation. Blood pressure and heart rate were measured continuously with telemetry in Sprague - Dawley rats of four experimental groups: nonpregnant controls, Suramin-treated nonpregnant rats, pregnant controls and pregnant Suramin-treated rats. Blood samples were collected before pregnancy and at gestational day 20 for analysis of renin and sFIt-1. The fetal and placental morphology were evaluated after caesarian section on gestational day 20. Results The blood pressure of the pregnant Suramin-treated rats successively increased during pregnancy and differed by 17 mmHg at gestational day 20 compared with the pregnant control rats. In the pregnant Suramin-treated rats group, the renin levels increased (+122%) and the sFIt-1 levels decreased (-58%) during pregnancy. The pregnant Suramin-treated fetuses and placentae were smaller (2.8 g and 0.51 g) than the pregnant controls rats' fetuses and placentae (3.5g and 0.56g). Resorptions tended to be higher in the pregnant Suramin-treated rat litters compared with the pregnant control rat litters (P = 0.08). The area of the maternal blood vessels in the mesometrial triangle was smaller in the pregnant Suramin-treated rats group than in the pregnant control rats group. Conclusion The inhibition of uterine angiogenesis increases maternal blood pressure and compromises fetal and placental development. Placental hypoxia and subsequent activation of the renin-angiotensin system may play an important role for the hypertension. J Hypertens 27:829-837 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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| 46. |
- Carlström, Mattias, et al.
(författare)
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Hydronephrosis causes salt-sensitive hypertension in rats
- 2006
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Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352 .- 1473-5598. ; 24:7, s. 1437-1443
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hypertension is a common disease in the Western world and approximately 5% of all cases are secondary to kidney malfunction. It is not clear whether unilateral hydronephrosis due to partial obstruction affects blood pressure. AIM: The aim of this study was to determine whether hypertension develops and to investigate the effects of different salt diets on the blood pressure in hydronephrotic animals. METHODS: Unilateral partial ureteral obstruction was created in 3-week-old Sprague-Dawley rats. A telemetric device was implanted 4-6 weeks later and blood pressure was measured on normal, low- and high-salt diets. Plasma samples were collected on all diets for renin analysis. RESULTS: All hydronephrotic animals developed hypertension that correlated to the degree of hydronephrosis. The blood pressure increased slowly with time and was salt sensitive. In severe hydronephrosis, blood pressure increased from 118 ± 5 mmHg on low salt to 140 ± 6 mmHg on high salt intake, compared to control levels of 82 ± 2 and 84 ± 2 mmHg, respectively. Plasma renin concentration was increased in the hydronephrotic group of animals compared to controls on all diets, but the difference was only significant on a normal salt diet, 165 ± 15 versus 86 ± 12 μGU/ml respectively. In animals with severe hydronephrosis the plasma renin levels were lower, and the changes less, than in those with mild and moderate hydronephrosis. CONCLUSION: This study demonstrates the presence of a salt-sensitive hypertension in hydronephrosis. A systemic effect of the renin-angiotensin system alone cannot be responsible for the hypertension.
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| 47. |
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| 48. |
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| 49. |
- Castiglioni, Laura, et al.
(författare)
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Fenofibrate attenuates cardiac and renal alterations in young salt-loaded spontaneously hypertensive stroke-prone rats through mitochondrial protection
- 2018
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Ingår i: Journal of Hypertension. - : LIPPINCOTT WILLIAMS & WILKINS. - 0263-6352 .- 1473-5598. ; 36:5, s. 1129-1146
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:The simultaneous presence of cardiac and renal diseases is a pathological condition that leads to increased morbidity and mortality. Several lines of evidence have suggested that lipid dysmetabolism and mitochondrial dysfunction are pathways involved in the pathological processes affecting the heart and kidney. In the salt-loaded spontaneously hypertensive stroke-prone rat (SHRSP), a model of cardiac hypertrophy and nephropathy that shows mitochondrial alterations in the myocardium, we evaluated the cardiorenal effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR) agonist that acts by modulating mitochondrial and peroxisomal fatty acid oxidation.Methods:Male SHRSPs aged 6-7 weeks were divided in three groups: standard diet (n=6), Japanese diet with vehicle (n=6), and Japanese diet with fenofibrate 150mg/kg/day (n=6) for 5 weeks. Cardiac and renal functions were assessed in vivo by MRI, ultrasonography, and biochemical assays. Mitochondria were investigated by transmission electron microscopy, succinate dehydrogenase (SDH) activity, and gene expression analysis.Results:Fenofibrate attenuated cardiac hypertrophy, as evidenced by histological and MRI analyses, and protected the kidneys, preventing morphological alterations, changes in arterial blood flow velocity, and increases in 24-h proteinuria. Cardiorenal inflammation, oxidative stress, and cellular senescence were also inhibited by fenofibrate. In salt-loaded SHRSPs, we observed severe morphological mitochondrial alterations, reduced SDH activity, and down-regulation of genes regulating mitochondrial fatty-acid oxidation (i.e. PPAR, SIRT3, and Acadm). These changes were counteracted by fenofibrate. In vitro, a direct protective effect of fenofibrate on mitochondrial membrane potential was observed in albumin-stimulated NRK-52E renal tubular epithelial cells.Conclusion:The results suggest that the cardiorenal protective effects of fenofibrate in young male salt-loaded SHRSPs are explained by its capacity to preserve mitochondrial function.
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| 50. |
- Cederholm, Jan, et al.
(författare)
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Blood pressure and risk of cardiovascular diseases in type 2 diabetes : further findings from the Swedish National Diabetes Register (NDR-BP II)
- 2012
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 30:10, s. 2020-2030
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Estimate risks of coronary heart disease (CHD), stroke and cardiovascular disease (CVD) with updated mean systolic (SBP) and diastolic (DBP) blood pressure in an observational study of patients with type 2 diabetes. Methods: Thirty-five thousand and forty-one patients treated with antihypertensive drugs, and 18 512 untreated patients, aged 30-75 years, without previous heart failure, followed for 6 years until 2009. Results: In treated patients, nonlinear splines for 6-year risk of fatal/nonfatal CHD, stroke and CVD by BP as a continuous variable showed a progressive increase with higher SBP from 140 mmHg and higher, and with DBP from 80 mmHg, with a J-shaped risk curve at lowest SBP levels, but not obviously at lowest DBP levels. Analysing intervals of SBP with 130-134 mmHg as reference at Cox regression, adjusted hazard ratios (HR) for fatal/nonfatal CHD, stroke and CVD with at least 140 mmHg were 1.22 [95% confidence interval (CI): 1.08-1.39], 1,43 (1.18-1.72), 1.26 (1.13-1.41), all P<0.001. HR with 115-129 and 135-139 mmHg were nonsignificant, whereas increased with 100-114 mmHg, 1.96 (P<0.001), 1.75 (P=0.02), 2.08 (P < 0.001), respectively. With DBP 75-79 mmHg as reference, adjusted HR for fatal/nonfatal CHD, stroke and CVD with DBP 80-84 mmHg were 1.42 (1.26-1.59), 1.46 (1.24-1.72), 1.39 (1.26-1.53), all P< 0.001. Corresponding HR with DBP at least 85 mmHg were 1.70 (1.50-1.92), 2.35 (1.99-2.77), 1..87 (1.69-2.07), all P < 0.001. Corresponding HR with DBP 60-69 and 70-74 mmHg were nonsignificant. The picture was similar in 7059 patients with previous CVD and in untreated patients. Conclusion: BP around 130-135/75-79 mmHg showed lower risks of cardiovascular diseases in patients with type 2 diabetes.
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