Shota Hamada

Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of Age

Background: Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ≥80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death. Methods: A population-based cohort study was conducted using electronic health records of 144 403 participants ≥80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ⩽5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportional-hazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death. Results: During follow-up, 51 808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110 to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40–6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30–7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life. Conclusions: A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life.

Mortality in Individuals Aged 80 and Older with Type 2 Diabetes Mellitus in Relation to Glycosylated Hemoglobin, Blood Pressure, and Total Cholesterol

To evaluate whether low glycosylated hemoglobin (HbA1c), blood pressure (BP), and total cholesterol (TC) are associated with lower risk of all‐cause mortality in very old individuals with type 2 diabetes mellitus.

Longitudinal Trends in Hypertension Management and Mortality Among Octogenarians: Prospective Cohort Study

The role of hypertension management among octogenarians is controversial. In this long-term follow-up (>10 years) study, we estimated trends in hypertension prevalence, awareness, treatment, and control among octogenarians, and evaluated the relationship of systolic blood pressure (SBP) ranges with mortality. Data were based on the English Longitudinal Study of Ageing (ELSA). Outcome measures were hypertension prevalence, awareness, treatment and control, and cardiovascular disease, and all-cause mortality events. Participants were separated into 8 categories of SBP values (<110, 110–119, 120–129, 130–139, 140–149, 150–159, 160–169, and >169 mm Hg). Among 2692 octogenarians, mean SBP levels declined from 147 mm Hg in 1998/2000 to 134 mm Hg in 2012/2013. The decline was of lower magnitude in the 50 to 79 years old subgroup (n=22007). Hypertension prevalence and awareness were 40% and 13%, respectively, higher among octogenarians than the 50 to 79 years of age subgroup, but hypertension treatment rates were similar (≈90%). Around 47% of the treated octogenarians achieved conventional BP targets (<140/90 mm Hg), increasing to 59% when assessed against revised targets (<150/90 mm Hg). All-cause mortality rates were higher (hazard ratio, 1.55; 95% confidence interval, 0.89–2.72) at lower extremes of SBP values (<110 mm Hg). The lowest cardiovascular disease and all-cause mortality risk among treated octogenarians was observed for an SBP range of 140 to 149 mm Hg (1.04, 0.60–1.78) and 160 to 169 mm Hg (0.78, 0.51–1.21). An increasing trend in hypertension awareness and treatment was observed in a large sample of community-dwelling octogenarians. The results do not support the view that more stringent BP targets may be associated with lower mortality.

Antidiabetic and cardiovascular drug utilisation in patients diagnosed with type 2 diabetes mellitus over the age of 80 years: a population-based cohort study

BACKGROUND there is a lack of evidence to inform treatment recommendations for very old people with type 2 diabetes mellitus (T2DM). OBJECTIVE to evaluate trends in antidiabetic and cardiovascular drug utilisation for patients developing T2DM over 80 years of age. METHODS a population-based cohort was sampled from the UK Clinical Practice Research Datalink between 1990 and 2013. Eligible patients were those with T2DM diagnosed after the age of 80 years and prescribed antidiabetic drugs. RESULTS twelve thousand eight hundred and eighty-one patients, with 61% of females, were included. From 1990 to 2013, use of sulphonylureas declined from 94 to 29%, while metformin use increased from 22 to 86%. Prescribing of antihypertensive drugs increased substantially from 46 to 77%, lipid-lowering drugs from 1 to 64%, antiplatelets from 34 to 47% and oral anticoagulants from 5 to 19%. Women were more frequently prescribed antihypertensive drugs (odds ratio 1.26, 95% confidence interval 1.17 to 1.37) but less prescribed antiplatelets (0.83, 0.78 to 0.89). Compared with those diagnosed with T2DM from 80 to 89 years (n = 11,467, 89%), patients diagnosed after the age of 90 years (n = 1,414, 11%) were less likely to be prescribed insulin (0.37, 0.24 to 0.58), metformin (0.67, 0.60 to 0.75), antihypertensive drugs (0.42, 0.38 to 0.48), lipid-lowering drugs (0.26, 0.23 to 0.30) and anticoagulants (0.55, 0.44 to 0.68). CONCLUSIONS there have been major increases in the intensity of pharmacological management of patients diagnosed with T2DM over 80 years of age, but the effectiveness and safety of these interventions in very old people require further evaluation.

Systolic Blood Pressure Trajectory, Frailty and All-Cause Mortality Over 80 Years of Age. Cohort Study Using Electronic Health Records

Background: Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ≥80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death. Methods: A population-based cohort study was conducted using electronic health records of 144 403 participants ≥80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ⩽5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportional-hazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death. Results: During follow-up, 51 808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110 to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40–6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30–7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life. Conclusions: A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life.

Declining blood pressure and intensification of blood pressure management among people over 80 years: Cohort study using electronic health records

Background: Management of high blood pressure (BP) in people over 80 years is controversial, but there is limited information available concerning the uptake of hypertension treatment at this age. Objective: To evaluate use of antihypertensive drugs and changes in SBP and DBP from 2001 to 2014 in men and women aged 80 years and over. Methods: Cohort study using primary care electronic health records of 265 225 participants from the UK Clinical Practice Research Datalink. Records of BP and antihypertensive medications were analysed. Linear trends were estimated by frailty category in multiple regression models. Results: Data were analysed for 116 401 men and 148 824 women. The proportion with BP recorded increased from 51% in 2001 to 78% in 2014. The proportion of patients prescribed antihypertensive medications increased from 64 to 76%. Mean SBP declined from 150 (SD 20) mmHg in 2001 to 135 (16) mmHg in 2014. In ‘fit’ participants, the decline in SBP was 12.4 (95% confidence interval 11.9–13.0) mmHg/decade in those treated for hypertension and 8.5 (7.8–9.1) mmHg in those not treated. The decline in SBP was smaller as frailty increased. The proportion of all participants with BP less than 140/90 mmHg increased from 14 to 44% in the study period. Conclusion: In octogenarians, BP treatment has intensified between 2001 and 2014. BP values have declined in both treated and untreated participants, with a substantial increase in the proportion achieving conventional BP targets.

Trajectory of Total Cholesterol in The Last Years of Life Over Age 80 Years. Cohort Study of 99,758 Participants.

Background Epidemiological studies suggest that lower total cholesterol (TC) may be associated with higher mortality. This study aimed to evaluate whether a decline in TC before death might account for the association of TC with mortality over age 80 years. Methods Cohort study using primary care electronic health records of 99,758 participants aged 80-105 years from the UK Clinical Practice Research Datalink. Hazard ratios for all-cause mortality were adjusted for age, gender, frailty, comorbidity, blood pressure, and smoking. Fractional polynomial models were fitted to evaluate longitudinal trends in TC before death or end-of-study. Adjusted odds ratios were estimated using generalized estimating equations. Results There were 63,630 women and 36,128 men, mean age 86 years, with 29,200 deaths. There were 41,164 treated with statins at cohort entry. Compared with TC values of 4.5-5.4 mmol/L, TC values <3.0 mmol/L were associated with higher mortality (statin treated hazard ratios 1.53, 95% confidence interval 1.43-1.64, p < .001; not treated, 1.41, 1.29-1.54, p < .001). A secular decline in TC values accelerated in the last 2 years of life. In the last quarter of follow-up, the adjusted odds of TC < 3.0 mmol/L for those who died, compared with surviving participants, were 3.33 (2.84-3.91, p < .001) for untreated and 1.88 (1.68-2.11, p < .001) for statin-treated participants. Conclusions TC values show a terminal decline in the last years of life. Reverse causation may contribute to the association of lower TC with higher mortality in nonrandomized studies.

Multiple risk factor control, mortality and cardiovascular events in type 2 diabetes and chronic kidney disease: a population-based cohort study

Objectives This study aimed to evaluate the effectiveness of multiple risk factor control (MRFC) at reducing mortality and cardiovascular events in diabetes and chronic kidney disease (CKD) in clinical practice. Design Population-based cohort study. Setting Primary care database in the UK, linked with inpatient and mortality data. Participants Participants aged 40–79 years with type 2 diabetes and valid serum creatinine measurements, including 11 431 participants with CKD (estimated glomerular filtration rate: eGFR 15–59 mL/min/1.73 m2) and 36 429 participants with non-CKD (eGFR ≥60 mL/min/1.73 m2). Exposures MRFC consisted of four components: Haemoglobin A1c (HbA1c) <53 mmol/mol (<7.0%), blood pressure <140/90 mm Hg, total cholesterol <5 mmol/L and no smoking. The main exposure variable was the number of risk factors controlled at baseline. Outcome measures All-cause and cardiovascular mortality in the overall participants. Cardiovascular events, including coronary heart disease and stroke, in participants limited to those without a history of cardiovascular diseases at baseline. Results In participants with CKD, 37% or 13% met three or four MRFC criteria, respectively. Increasing numbers of risk factors controlled were associated with lower relative hazards for all outcomes studied compared with those meeting no or one criterion. For participants with CKD meeting four criteria, the adjusted HR for all-cause mortality was 0.60 (95% CI 0.53 to 0.69) and the adjusted subdistribution HR for cardiovascular mortality was 0.60 (95% CI 0.50 to 0.70), considering a competing risk of non-cardiovascular death. Participants meeting four criteria also had lower relative hazards for coronary heart disease (adjusted subdistribution HR 0.73, 95% CI 0.59 to 0.91) and stroke (0.63, 95% CI 0.45 to 0.89), considering death as a competing risk. Conclusions MRFC may lower the increased risks for mortality and cardiovascular events in people with diabetes and CKD. Further research is needed to evaluate appropriateness of MRFC according to individual participants’ health status for improved management of cardiovascular risks in this population.

Longitudinal Trends in Hypertension Management and Mortality Among Octogenarians

The role of hypertension management among octogenarians is controversial. In this long-term follow-up (>10 years) study, we estimated trends in hypertension prevalence, awareness, treatment, and control among octogenarians, and evaluated the relationship of systolic blood pressure (SBP) ranges with mortality. Data were based on the English Longitudinal Study of Ageing (ELSA). Outcome measures were hypertension prevalence, awareness, treatment and control, and cardiovascular disease, and all-cause mortality events. Participants were separated into 8 categories of SBP values (<110, 110–119, 120–129, 130–139, 140–149, 150–159, 160–169, and >169 mm Hg). Among 2692 octogenarians, mean SBP levels declined from 147 mm Hg in 1998/2000 to 134 mm Hg in 2012/2013. The decline was of lower magnitude in the 50 to 79 years old subgroup (n=22007). Hypertension prevalence and awareness were 40% and 13%, respectively, higher among octogenarians than the 50 to 79 years of age subgroup, but hypertension treatment rates were similar (≈90%). Around 47% of the treated octogenarians achieved conventional BP targets (<140/90 mm Hg), increasing to 59% when assessed against revised targets (<150/90 mm Hg). All-cause mortality rates were higher (hazard ratio, 1.55; 95% confidence interval, 0.89–2.72) at lower extremes of SBP values (<110 mm Hg). The lowest cardiovascular disease and all-cause mortality risk among treated octogenarians was observed for an SBP range of 140 to 149 mm Hg (1.04, 0.60–1.78) and 160 to 169 mm Hg (0.78, 0.51–1.21). An increasing trend in hypertension awareness and treatment was observed in a large sample of community-dwelling octogenarians. The results do not support the view that more stringent BP targets may be associated with lower mortality.

Drug prescribing during the last year of life in very old people with diabetes

Abstract Objective to evaluate primary care drug utilisation during the last year of life, focusing on antidiabetic and cardiovascular drugs, in patients of advanced age with diabetes. Design population-based cohort study. Setting primary care database in the UK. Subjects patients with type 2 diabetes who died at over 80 years of age between 2011 and 13. Methods main outcome measures included proportions of patients prescribed different classes of drugs, comparing the first (Q1) and the fourth quarters (Q4) of the last year of life. Results the study included 5,324 patients, with the median age 86 years and 50% female. Three-fourths of the patients received five or more drugs, and the total number of drugs prescribed was almost stable at 6.2 ± 3.1 (mean ± SD) during the last year of life. Substantial proportions of patients were treated with antidiabetic drugs (78%), antihypertensive drugs (76%), statins (62%) and low-dose aspirin (46%) in Q1. Prescribing of these drugs slightly decreased by 3–8% in Q4. There were increases in prescribing of anti-infectives (35% in Q1 to 50% in Q4), drugs for nervous system (63% to 73%), drugs for respiratory system (24% to 33%) and systemic hormonal drugs (22% to 27%). Conclusion patients of advanced age with type 2 diabetes were often treated with antidiabetic and cardiovascular drugs even when approaching death. More research is needed to generate evidence to guide optimal drug utilisation for older people with a limited life expectancy.