trials have used dementia as an outcome.6,19 – 21 We will focus here on studies with dementia outcomes and with follow-up of .1 year. Of the double-blind placebo-controlled trials carried out in older adults, the results of Syst-Eur stand out. They reported a significant 50% reduction in incident dementia over a mean follow-up of 2 years in those aged 60 or over (from 7.7/1000 patient years in the placebo group to 3.8 in the actively treated group).19 Systolic Hypertension in the Elderly Program (mean age 72) found a non- significant effect of treatment, with 36 (1.5%) incident cases in the active group and 44 (1.9%) in the placebo group.6 The Perindopril Protection against Recurrent Stroke Study (PROGRESS) trial, a sec- ondary prevention population post stroke or transient ischaemic attack (mean age 64 years) found fewer cases in the actively treated groups but no significant differences overall. When incident dementia was combined with recurrent stroke, the outcome
became significant in favour of the actively treated group.20 Hypertension in the Very Elderly Trial reported higher rates of in- cident dementia, as would be expected in an older population and fewer cases in the active group although this was not significant (HR 0.86, 95% CI 0.67 – 1.09).21 Open-label trials have reported similar results and there have been several meta-analyses. Each has combined a slightly different selection of trials but all report a point estimate ,1.0, with just one reaching significance (HR 0.87, 95% CI 0.76–1.00, P 1⁄4 0.045).21 The results of Syst-Eur may be a chance finding or may reflect CCB use conferring some additional benefit either in terms of lowering the risk of ischaemic events or in relation to Alzheimer’-type pathology.22 Currently, therefore, there is no overwhelming evidence that treating hypertension in the very elderly prevents dementia but equally there is no evidence that treat-
ment increases risk.A further factor to take into consideration in the very elderly is the
possibility of a J-shaped relationship between BP and cognitive decline or dementia, i.e. an increased risk associated with low as well as high BP. There has been the suggestion that there may be a J-shape at least for diastolic pressure and cognitive function given that the very elderly with stiffer arteries are potentially less capable of regulating cerebral perfusion.23 As BP tends to fall prior to a diag- nosis of dementia it is hard to fully disentangle such associations. It may be that BP lowering decreases risk in some and increases risk in others. Recent results from HYVET have reported a J-shape for dia- stolic BP, active treatment, and dementia although not for systolic BP and a wider pulse pressure had the strongest relationship with inci- dent dementia.24 The concept of a J-shape and an the appropriate BP goal when lowering pressure using antihypertensives in the very
elderly remains controversial and is an area that requires further studies designed specifically to address this issue. The results from HYVET would suggest a target of 150/80 mmHg in such a group. This does not rule out additional benefit from lower levels but such benefit cannot be assumed and adverse effects may occur.
Renal function and biochemistry
An area of concern when treating the very elderly is renal function. Hypertension and older age are both associated with an increased risk of impaired renal function. Research in hypertensive very elderly groups is limited and the equations used to calculate esti- mated glomerular filtration rate (eGFR) remain largely unvalidated in this group. In those aged 75 and over with an eGFR calculated using the CKD-EPI (Chronic Kidney disease epidemiology collabor- ation) equation, low eGFR has been associated with an increased risk of hospitalization and mortality independent of known cardiovas- cular co-morbidity at baseline.25 In HYVET, there was a suggestion of a U-shape with low (,45 mL/min/1.73 m2) and high (≥75 mL/min/ 1.73 m2) eGFR being associated with a potential increase in risk of later cardiovascular events and mortality albeit not significantly.26 It should be noted that those with significantly impaired renal function were excluded from HYVET. The pattern of results was similar when the analyses were repeated using different formulae for calculating eGFR, although each equation performed slightly differently.26 Active treatment in HYVET had no impact on eGFR or on creatinine, potassium, glucose or urea. There was a statistically but not clinically significant rise in uric acid over 12 but not 24 months with no increase in gout reported.
Fracture and falls
Those treating the very elderly with hypertension often express concern that BP lowering increases the risk of falling and thus fracture with the subsequent adverse outcomes that ensue. However, thiazide and thiazide-like diuretics have been associated with reduced risk of fracture, assumed to be due to inhibition in the distal nephron of the Na – Cl co-transporter leading to a hyperpolarization, increasing the electrical driving force for calcium reabsorption, subsequent decrease in urinary calcium loss and the suggestion that this could preserve bone mineral density.27,28 It has also been suggested that such drugs exert there effect on bone independent of their effect on the kidney via inhib- ition of Na – Cl transporter expressed on osteoblasts resulting indir- ectly in bone mineral formation.29
trials have used dementia as an outcome.6,19 – 21 We will focus here on studies with dementia outcomes and with follow-up of .1 year. Of the double-blind placebo-controlled trials carried out in older adults, the results of Syst-Eur stand out. They reported a significant 50% reduction in incident dementia over a mean follow-up of 2 years in those aged 60 or over (from 7.7/1000 patient years in the placebo group to 3.8 in the actively treated group).19 Systolic Hypertension in the Elderly Program (mean age 72) found a non- significant effect of treatment, with 36 (1.5%) incident cases in the active group and 44 (1.9%) in the placebo group.6 The Perindopril Protection against Recurrent Stroke Study (PROGRESS) trial, a sec- ondary prevention population post stroke or transient ischaemic attack (mean age 64 years) found fewer cases in the actively treated groups but no significant differences overall. When incident dementia was combined with recurrent stroke, the outcome became significant in favour of the actively treated group.20 Hypertension in the Very Elderly Trial reported higher rates of in- cident dementia, as would be expected in an older population and fewer cases in the active group although this was not significant (HR 0.86, 95% CI 0.67 – 1.09).21 Open-label trials have reported similar results and there have been several meta-analyses. Each has combined a slightly different selection of trials but all report a point estimate ,1.0, with just one reaching significance (HR 0.87, 95% CI 0.76–1.00, P 1⁄4 0.045).21 The results of Syst-Eur may be a chance finding or may reflect CCB use conferring some additional benefit either in terms of lowering the risk of ischaemic events or in relation to Alzheimer’-type pathology.22 Currently, therefore, there is no overwhelming evidence that treating hypertension in the very elderly prevents dementia but equally there is no evidence that treat- ment increases risk.A further factor to take into consideration in the very elderly is the possibility of a J-shaped relationship between BP and cognitive decline or dementia, i.e. an increased risk associated with low as well as high BP. There has been the suggestion that there may be a J-shape at least for diastolic pressure and cognitive function given that the very elderly with stiffer arteries are potentially less capable of regulating cerebral perfusion.23 As BP tends to fall prior to a diag- nosis of dementia it is hard to fully disentangle such associations. It may be that BP lowering decreases risk in some and increases risk in others. Recent results from HYVET have reported a J-shape for dia- stolic BP, active treatment, and dementia although not for systolic BP and a wider pulse pressure had the strongest relationship with inci- dent dementia.24 The concept of a J-shape and an the appropriate BP goal when lowering pressure using antihypertensives in the very elderly remains controversial and is an area that requires further studies designed specifically to address this issue. The results from HYVET would suggest a target of 150/80 mmHg in such a group. This does not rule out additional benefit from lower levels but such benefit cannot be assumed and adverse effects may occur. Renal function and biochemistry An area of concern when treating the very elderly is renal function. Hypertension and older age are both associated with an increased risk of impaired renal function. Research in hypertensive very elderly groups is limited and the equations used to calculate esti- mated glomerular filtration rate (eGFR) remain largely unvalidated in this group. In those aged 75 and over with an eGFR calculated using the CKD-EPI (Chronic Kidney disease epidemiology collabor- ation) equation, low eGFR has been associated with an increased risk of hospitalization and mortality independent of known cardiovas- cular co-morbidity at baseline.25 In HYVET, there was a suggestion of a U-shape with low (,45 mL/min/1.73 m2) and high (≥75 mL/min/ 1.73 m2) eGFR being associated with a potential increase in risk of later cardiovascular events and mortality albeit not significantly.26 It should be noted that those with significantly impaired renal function were excluded from HYVET. The pattern of results was similar when the analyses were repeated using different formulae for calculating eGFR, although each equation performed slightly differently.26 Active treatment in HYVET had no impact on eGFR or on creatinine, potassium, glucose or urea. There was a statistically but not clinically significant rise in uric acid over 12 but not 24 months with no increase in gout reported. Fracture and falls Those treating the very elderly with hypertension often express concern that BP lowering increases the risk of falling and thus fracture with the subsequent adverse outcomes that ensue. However, thiazide and thiazide-like diuretics have been associated with reduced risk of fracture, assumed to be due to inhibition in the distal nephron of the Na – Cl co-transporter leading to a hyperpolarization, increasing the electrical driving force for calcium reabsorption, subsequent decrease in urinary calcium loss and the suggestion that this could preserve bone mineral density.27,28 It has also been suggested that such drugs exert there effect on bone independent of their effect on the kidney via inhib- ition of Na – Cl transporter expressed on osteoblasts resulting indir- ectly in bone mineral formation.29
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การทดลองได้ใช้
ภาวะสมองเสื่อมเป็นชนวน . 6,19 – 21 เราจะเน้นในการศึกษากับภาวะสมองเสื่อม และด้วยการติดตามผล 1 ปี ของทำให้และการทดลองดำเนินการในผู้สูงอายุ ผลลัพธ์ที่ได้จากระบบ EUR ยืนออก พวกเขารายงานที่สำคัญลด 50% ในภาวะเหตุการณ์กว่าหมายถึงการติดตาม 2 ปีในผู้ที่มีอายุ 60 หรือมากกว่า ( จาก 77 / 1 , 000 ปี ในผู้ป่วยกลุ่มยาหลอกถึง 3.8 ในงานดูแลกลุ่ม ) 19 , ความดันโลหิตสูงในผู้สูงอายุ ( อายุเฉลี่ย ( 72 ) พบว่าไม่มีผลต่อการรักษา กับ 36 ( 1.5% ) เหตุการณ์คดีในกลุ่มที่ใช้งานและ 44 ( 1.9% ) ใน 6 กลุ่มยาหลอก เพอรินโดพริลป้องกันศึกษาจังหวะกำเริบ ( ความคืบหน้า ) ทดลองวินาที - ondary การป้องกันประชากรโพสต์จังหวะหรือกัลปพฤกษ์ ( อายุเฉลี่ย 64 ปี ) พบผู้ป่วยน้อยกว่าในงานกลุ่ม แต่ไม่แตกต่างกัน โดยรวม เหตุการณ์ที่เกิดขึ้นเมื่อจิตบวกกับจังหวะผล
กลายเป็นอย่างมีนัยสำคัญในความโปรดปรานของงานดูแลกลุ่ม20 ความดันโลหิตสูงในการทดลองมากแก่รายงานอัตราที่สูงใน cident โรคสมองเสื่อม โดยคาดว่าจะเป็นในประชากรสูงอายุ และกรณีน้อยกว่าในกลุ่มที่ใช้งานถึงแม้ว่านี้ไม่แตกต่างกัน ( HR 0.86 , 95%CI เท่ากับ 0.67 ( 1.09 ) 21 เปิดป้ายได้รายงานผลการทดลองที่คล้ายกันและมีหลายโดยวิธีการวิเคราะห์เมต้า .แต่ละมีการรวมกันที่แตกต่างกันเล็กน้อย แต่การเลือกของการรายงานประมาณการจุด , 1.0 , มีเพียงหนึ่งถึงความสำคัญ ( HR 0.87 , 95% CI เท่ากับ 0.76 และ 1.00 , P 1 ⁄ 4 0.045 ) 21 ผลลัพธ์ของระบบยูโรอาจจะมีโอกาสหาหรืออาจสะท้อน CCB ใช้บางหารือผลประโยชน์เพิ่มเติมทั้งในแง่ ลดความเสี่ยงของเหตุการณ์ ischaemic หรือในความสัมพันธ์กับโรคประเภทอัลไซเมอร์ ' -22 ในปัจจุบัน จึงทำให้ไม่มีหลักฐานว่ายุ่งยากรักษาโรคความดันโลหิตสูงในผู้สูงอายุป้องกันโรคสมองเสื่อมมาก แต่อย่างเท่าเทียมกัน ไม่มีหลักฐานว่าปฏิบัติ -
การเพิ่มความเสี่ยง นอกจากนี้ ในการพิจารณา ในมาก ความเป็นไปได้ของผู้สูงอายุ
j-shaped ความสัมพันธ์ระหว่างความดันและปฏิเสธการรับรู้ หรือ โรคสมองเสื่อม ได้แก่
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