Outcomes of Treated Hypertension at Age 80 and Older

Cohort Analysis of 79,376 Individuals

João Delgado, PhD; Jane A. H. Masoli, MBChB; Kirsty Bowman, MPH; W. David Strain, MD; George A. Kuchel, MD; Kate Walters, PhD; Louise Lafortune, PhD; Carol Brayne, MD; David Melzer, PhD; Alessandro Ble, MD

Disclosures

J Am Geriatr Soc. 2017;65(5):995-1003. 

In This Article

Methods

Data Source

The CPRD is the English National Health Service (NHS) observational data service, with more than 11.3 million patients from 674 U.K. primary care practices.[8] CPRD data from primary care linked to Hospital Episode Statistics (HES) data for hospital admissions and diagnosis and Office for National Statistics (ONS) death certificate data were used. The data include information on individuals living in institutionalized care settings, as well as community-dwelling older people, and registration with primary care is very near complete for the older population in England.[8] The data have been shown to be representative of the U.K. population in terms of age and sex.[8]

Study Population

All adults in CPRD aged 80 and older with diagnosed hypertension who had at least three blood pressure (BP) measurements during a 3-year lead-in period and were prescribed at least one class of antihypertensive medication (alpha-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, beta-blockers, calcium channel blockers, centrally active antihypertensives, diuretics, renin inhibitors) before the lead-in period and during the follow-up period were included. The distribution of the classes of antihypertensive medication prescribed according to attained blood SBP is shown in Table S1. The earliest start date for the lead-in period was January 1, 2000. Primary care Read (diagnostic) codes as defined by NHS Quality of Outcomes Framework rules[9] and International Classification of Diseases, Tenth Revision (ICD-10) codes in HES[10] were used to identify individuals with hypertension.

Individuals with comorbidities that require specialized treatment or might introduce confounding (reverse causation with the comorbidity reducing BP) were excluded. Diagnoses excluded at baseline were dementia, cancer, stroke, heart failure, coronary heart disease, and end-stage renal failure (diagnosis of chronic kidney disease Stage 5 from CPRD or HES or dialysis code in CPRD, HES, or Office of Population Censuses and Surveys Classification of Interventions and Procedures version 4) (Figure S1).[10,11] Sensitivity analyses on the effect of excluding individuals with diabetes mellitus or chronic obstructive pulmonary disease (conditions that might particularly affect management of hypertension in their late stages) on all-cause mortality did not significantly alter results, so such individuals were not excluded (Table S2).

BP Data

BP was measured during routine general practitioner (GP) visits and recorded by the GP, nurse, or other practice staff,[8] normally in a sitting position at rest.[4] Measurements were excluded if they did not record SBP and diastolic BP (DBP). Individual measurements with extreme values (<0.15 and >99.85 centile) (SBP: <85 mmHg and > 224 mmHg; DBP: <46 mmHg and >120 mmHg) were excluded. The median of BP measurements recorded during the lead-in period were used to estimate stable treated baseline SBP and DBP; the median was used to avoid biases from extreme measures during acute clinical events. The average number of BP measurements according to SBP category varied from 7.2 for less than 125 mmHg to 13.4 for 165 to 174 mmHg (Table S3); 15,265 individuals diagnosed with and treated for hypertension had fewer than three BP measurements (Figure S1). This excluded group had a higher prevalence of dementia and heart failure at baseline, which would have triggered exclusion anyway. (This group may have fewer BPs recorded in primary care because of greater specialist input in secondary care.) Median SBP was categorized as less than 125 mmHg, 125 to 134 mmHg, 135 to 144 mmHg, 145 to 154 mmHg, 155 to 164 mmHg, 165 to 174 mmHg, 175 to 184 mmHg, and 185 mmHg and greater.

Covariates

Sex, age at beginning of follow-up, quintile of 2010 English Index of Multiple Deprivation for England (based on GP's postcode, as a proxy for socioeconomic status), and smoking status (from recorded GP Read terms, classified as current or recent smoker, exsmoker, and never smoker over the 10 years before study entry) were adjusted for in the statistical modelling. Adjusting for year of beginning of follow-up did not significantly affect estimates, so it was not included in the final models. Sensitivity analyses of the effect of comorbidity (Charlson Comorbidity Index[12]), major weight loss (a history of weight loss of ≥10% in the 5 years before baseline), body mass index (BMI), and exclusion of individuals in institutional settings on the association between SBP and all-cause mortality did not significantly alter the results. Individuals in institutional settings during the 3-year lead-in period of analysis were identified through recorded contacts in residential or nursing homes with doctors or other practice staff. When testing for confounding, stratified survival analyses were selected when adjustment for the tested covariate violated hazard proportionality.[13] Therefore, because this analysis aimed to estimate overall prognosis for the defined complete group of typical patients, individuals were not excluded based on these factors. Neither were these factors further adjusted for in the main analyses, because that might have adjusted away intermediate pathology on the causal pathway to outcomes, potentially introducing bias, and would have made estimates difficult to interpret for routine clinical practice.[14]

Outcomes

The outcomes of interest for this analysis were all-cause mortality, cardiovascular events (ischemic stroke, myocardial infarction (MI), heart failure), and fragility fractures. Outcomes were considered if the event occurred while the participant was registered with a practice and the practice data quality was classified as up-to standard according to CPRD. Fragility fractures are pathological fractures that occur as part of normal activities such as falling from a standing height and are often associated with osteoporosis.[15] Only the commonest fragility fractures were included, to increase specificity: hip, vertebrae, humerus, distal radius, pelvis or pubic ramus, and ankle. Data for outcomes were obtained from participant HES data. For MI and fragility factors, ICD-10 codes were supplemented with procedural coding from Office of Population Censuses and Surveys Classification of Interventions and Procedures version 4.[10,11]

Statistical Analysis

Cox proportional hazards models were used to estimate associations between BP and mortality outcomes. Competing-risk survival models were used for incident stroke, MI, heart failure, and fragility fractures, with all-cause mortality as a competing risk.[16] For all survival analyses, the attained SBP of 145 to 154 mmHg (with midpoint 150 mmHg) was used as the reference category, because it lies within most international BP targets for older people.[17] For all outcomes, the numbers needed to treat or harm were calculated using the Altman and Anderson method.[18] All statistical analyses were conducted using Stata version 13 (Stata Corp., College Station, TX). In the main analyses, 12,854 individuals were excluded because of missing information on smoking habits, and an additional 32 were excluded for missing information on Index of Multiple Deprivation (Figure S1).

Ethical and Scientific Approval

The CPRD has been granted multiple research ethics committee approval (05/MRE04/87) to undertake purely observational studies, with external data linkages including HES and ONS mortality data. The work of CPRD is also covered by National Information Governance Board for Health and Social Care Ethics and Confidentiality Committee approval ECC 5–05 (a) 2012.

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