| 11. |
- 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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| 12. |
- 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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| 13. |
- Chittani, Martina, et al.
(författare)
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TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.
- 2015
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Ingår i: Journal of Hypertension. - 1473-5598. ; 33:6, s. 1301-1309
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Tidskriftsartikel (refereegranskat)abstract
- Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects.
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| 14. |
- Cunha, Pedro G, et al.
(författare)
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Pulse wave velocity distribution in a cohort study: from arterial stiffness to early vascular aging.
- 2015
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Ingår i: Journal of Hypertension. - 1473-5598. ; 33:7, s. 1438-1445
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Tidskriftsartikel (refereegranskat)abstract
- By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population.
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| 15. |
- Fawad, Ayesha, et al.
(författare)
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1C.07: PRONEUROTENSIN INDEPENDENTLY PREDICTS CARDIOVASCULAR DISEASE. THE MALMÖ PREVENTIVE PROJECT.
- 2015
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Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 1473-5598 .- 0263-6352. ; 33 Suppl 1, s. 11-11
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Tidskriftsartikel (refereegranskat)abstract
- Neurotensin is released from the gut after fat intake and has a role in appetite regulations. Proneurotensin is a stable fragment of the neurotensin precursor hormone and fasting plasma proneurotensin levels have shown to be significantly associated with the development of cardiovascular disease in middle aged participants of the Malmö Diet and Cancer Study. Here, we aimed at replicating the initial findings in an independent second cohort and to extend its validity to an older population.
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| 16. |
- Fedorova, Olga V, et al.
(författare)
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Plasma level of the endogenous sodium pump ligand marinobufagenin is related to the salt-sensitivity in men.
- 2015
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Ingår i: Journal of Hypertension. - 1473-5598. ; 33:3, s. 534-541
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Tidskriftsartikel (refereegranskat)abstract
- Salt-induced elevation of the endogenous digitalis like sodium pump ligand marinobufagenin (MBG) in the Dahl salt-sensitive rats resulted in elevated blood pressure (BP). Here, we tested, in humans, whether MBG levels are related to ambulatory 24-h BP (ABP), controlled long-term increase of salt-intake induces changes in MBG and any salt-induced change in MBG is related to salt sensitivity.
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| 17. |
- Gottsäter, Mikael, et al.
(författare)
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Non-hemodynamic predictors of arterial stiffness after 17 years of follow-up: the Malmö Diet and Cancer study.
- 2015
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Ingår i: Journal of Hypertension. - 1473-5598. ; 33:5, s. 957-965
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Tidskriftsartikel (refereegranskat)abstract
- Arterial stiffness plays a fundamental role in the development of hypertension and is a risk factor for both cardiovascular disease and mortality. The stiffening that occurs with increasing age has, in numerous cross-sectional studies, been shown to be associated with several cardiovascular risk factors. This observational study aims to characterize the predictive and cross-sectional markers focusing on the non-hemodynamic component of arterial stiffness.
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| 18. |
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| 19. |
- Holmqvist, Lina, et al.
(författare)
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Cardiovascular outcome in treatment-resistant hypertension: results from the Swedish Primary Care Cardiovascular Database (SPCCD).
- 2018
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Ingår i: Journal of hypertension. - 1473-5598. ; 36:2, s. 402-409
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Tidskriftsartikel (refereegranskat)abstract
- To assess cardiovascular outcome in patients with treatment-resistant hypertension (TRH) compared with patients with nontreatment-resistant hypertension (HTN).Cohort study with data from 2006 to 2012 derived from the Swedish Primary Care Cardiovascular Database with hypertensive patients aged at least 30 years. TRH was defined as blood pressure at least 140/90mmHg despite medication adherence to three or more dispensed antihypertensive drug classes. Patients with cardiovascular comorbidity were excluded. The association between TRH and cardiovascular events with adjustment for important confounders was analyzed.We included 4317 TRH patients and 32282 HTN patients. TRH patients (61% women) were older (70 vs. 66 years), had higher SBP (152 vs. 141mmHg) and more diabetes (30 vs. 20%) (P<0.001 for all) compared with HTN patients. Mean follow-up time was 4.3 years. In the adjusted analysis, TRH patients had an increased risk for total mortality [hazard ratio 1.12; 95% confidence interval (CI), 1.03-1.23], cardiovascular mortality (hazard ratio 1.20; 95% CI, 1.03-1.40) and incident heart failure (hazard ratio 1.34; 95% CI, 1.17-1.54) but not for incident stroke (hazard ratio 1.03; 95% CI, 0.90-1.19) or transitoric ischemic attack (hazard ratio 1.12; 95% CI, 0.86-1.46) compared with HTN patients.Patients with TRH have a poor prognosis beyond blood pressure level, compared with hypertensive patients without TRH. In particular, the high risk for heart failure is of clinical importance and merits further investigation.
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| 20. |
- Hörnsten, Carl, et al.
(författare)
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High blood pressure as a risk factor for incident stroke among very old people : a population-based cohort study
- 2016
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 34:10, s. 2059-2065
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: High blood pressure (BP) increases the risk of stroke, but there is limited evidence from studies including very old people. The aim was to investigate risk factors for incident stroke among very old people.METHODS: A prospective population-based cohort study was performed among participants aged at least 85 years in northern Sweden. The 955 participants were tested at their homes. BP was measured manually after 5-min supine rest. Incident stroke data were collected from medical charts guided by hospital registry, death records, and 5-year reassessments. Cox proportional hazards models were used.RESULTS: The stroke incidence was 33.8/1000 person-years (94 stroke events) during a mean follow-up period of 2.9 years. In a comprehensive multivariate model, atrial fibrillation [hazard ratio 1.85, 95% confidence interval (CI) 1.07-3.19] and higher SBP (hazard ratio 1.19, 95% CI 1.08-1.30 per 10-mmHg increase) were associated with incident stroke overall. However, higher SBP was not associated with incident stroke in participants with SBP less than 140 mmHg (hazard ratio 0.90, 95% CI 0.53-1.53 per 10-mmHg increase). In additional multivariate models, DBP at least 90 mmHg (hazard ratio 2.45, 95% CI 1.47-4.08) and SBP at least 160 mmHg (vs. <140 mmHg; hazard ratio 2.80, 95% CI 1.53-5.14) were associated with incident stroke. The association between BP and incident stroke was not affected by interactions related to sex, dependence in activities of daily living, or cognitive impairment.CONCLUSION: High SBP (≥160 mmHg) and DBP (≥90 mmHg) and atrial fibrillation appeared to be risk factors for incident stroke among very old people.
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