BACKGROUND The Systolic Blood Pressure Intervention Trial (SPRINT) and the Heart Outcomes Prevention Evaluation 3 (HOPE-3) trial demonstrated the merits of blood pressure (BP) lowering to reduce cardiovascular events in intermediate to high cardiovascular risk adults. However, the population impact of an absolute risk-based strategy for BP lowering remains unclear. METHODS We examined 3 treatment thresholds using the National Health and Nutrition Examination Survey. First, the JNC8 guideline was used to determine treatment goals. Second, adults with a systolic BP (SBP) of 130 mm Hg and high cardiovascular risk (based on eligibility for SPRINT) were considered eligible for additional BP lowering. Finally, we combined the treatment threshold for high-risk adults with an SBP treatment threshold of 140 mm Hg for intermediate-risk adults that met the eligibility criteria for HOPE-3. RESULTS Under the JNC8 guideline, 78.0% of adults ≥50 years were at target while 22.0% were eligible for additional BP lowering. If an SBP treatment threshold of 130 mm Hg was used for adults at high cardiovascular risk, 31.1% would be eligible for additional BP lowering (an increase of 8.1 million). If an SBP threshold of 140 mm Hg was additionally used for adults at intermediate risk, 31.4% of adults would be eligible for BP lowering (an increase of 8.3 million). The proportion of adults eligible for BP lowering with established coronary artery disease decreased with the risk-based strategies. CONCLUSION An absolute risk treatment strategy would modestly increase the proportion of adults eligible for BP lowering

Emdin, CA

Odutayo, Ayodele

Tennankore, KK

Emdin, Connor A

Oxford University Research Archive

 1 Abstract Word Count: 247 1 Text Word Count: 1386  2 Number of References: 12  3 Number of Tables: 1 4  5 Proportion and Characteristics of US Adults Who May Be Eligible from 6 Additional Blood Pressure Lowering Based On Absolute Risk 7  8  9 Ayodele A. Odutayo MD MSc1, Karthik K. Tennankore MD2, and Connor A. Emdin 10 BHSc3 11  12  13  14 1Brasenose College, University of Oxford, Oxford United Kingdom  15 2Dalhousie University/Capital Health, Halifax, Nova Scotia 16 3St John’s College, University of Oxford, Oxford, United Kingdom 17  18  19  20 AO: Ayodele.odutayo@bnc.ox.ac.uk; KT: KarthikK.Tennankore@nshealth.ca; CAE: 21 connor.emdin@sjc.ox.ac.uk 22  23  24  25  26  27  28  29  30  31  32 Disclosure: Nothing to Declare 33 Keywords: Blood Pressure; Absolute Risk; Epidemiology 34  35 Correspondence to: 36 Ayodele Odutayo 37 Brasenose College, 38 Radcliffe Square, 39 University of Oxford, 40 Oxfordshire, United Kingdom. 41 OX1 4AJ 42 Telephone: 07462113024 43 Email: Ayodele.odutayo@bnc.ox.ac.uk 44  45  46  2 ABSTRACT 47 Background: The Systolic Blood Pressure Intervention Trial (SPRINT) and the Heart 48 Outcomes Prevention Evaluation 3 (HOPE-3) trial demonstrated the merits of blood 49 pressure (BP) lowering to reduce the risk of cardiovascular events among adults at 50 intermediate to high cardiovascular risk. However, the population impact of an absolute 51 risk based strategy for blood pressure lowering remains unclear. 52  53 Methods: We examined three treatment thresholds using the National Health and 54 Nutrition Examination Survey. First, the JNC8 guideline was used to determine treatment 55 goals. Participants were considered “At target” if their BP was below target with or 56 without treatment. Participants were considered “Eligible for additional BP lowering” if 57 their BP was above target. Second, adults with a systolic blood pressure (SBP) of 130 58 mm Hg and high cardiovascular risk (≥15% using the Framingham risk equation or 59 eligible for SPRINT) were considered eligible for additional BP lowering. Finally, we 60 combined the treatment threshold for high risk adults with an SBP treatment threshold of 61 140 mm Hg for intermediate risk adults that met the eligibility criteria for HOPE-3. We 62 retained the targets in the JNC8 guideline for adults excluded from SPRINT and HOPE-3. 63  64 Results: Under the JNC8 guideline, 74.8% of adults ≥50 years were at target while 65 25.2% were eligible for additional BP lowering. If an SBP threshold of 130 mm Hg was 66 used for individuals at high cardiovascular risk, 36.4% of adults (8.1 million) would be 67 eligible for additional BP lowering. If an SBP threshold of 140 mmHg was additionally 68 used for adults at intermediate risk based on the HOPE-3 eligibility criteria, 36.6% of 69  3 adults (8.3 million) would be eligible for additional BP lowering. The proportion of 70 adults eligible for BP lowering with established cardiovascular disease decreased with the 71 risk based strategies. 72  73 Conclusion: An absolute risk treatment strategy would increase the proportion of adults 74 eligible for BP lowering. 75  76 77  4 INTRODUCTION 78 In a meta-analysis of blood pressure (BP) lowering trials, BP lowering resulted in 79 a consistent proportional risk reduction in cardiovascular disease (CVD){Law:2009wp} 80 down to a threshold of 120 mmHg systolic blood pressure (SBP). This finding was 81 reinforced by the Systolic Blood Pressure Intervention Trial (SPRINT) wherein BP 82 lowering to an SBP target of <120 mmHg relative to a target of <140 mm Hg reduced the 83 risk of major cardiovascular events by a third among adults at high cardiovascular 84 risk.{SPRINTResearchGroup:2015dw}A corresponding trial in adults at intermediate 85 cardiovascular risk also demonstrated that a 5 mmHg reduction in blood pressure was 86 associated with a lower risk of major cardiovascular events in adults with a baseline 87 blood pressure >140 mmHg {Lonn:2016fo}. 88  89 If absolute risk of CVD is considered in the initiation of BP lowering therapy, a 90 proportion of US adults at elevated cardiovascular risk with BP below current guideline 91 thresholds may warrant further BP lowering. However, the size and characteristics of this 92 population are currently unknown. To inform public health efforts, we estimated the 93 proportion and characteristics of United States (US) adults who may be eligible for 94 treatment based on their absolute risk of cardiovascular disease. 95  96 METHODS 97 The objective of our study was to estimate the number of adults that would warrant blood 98 pressure lowering treatment if an absolute cardiovascular risk strategy was used to 99 determine eligibility. 100  5 Study Sample 101 The National Health and Nutrition Examination Survey (NHANES) is a cross-sectional 102 survey on a representative sample of US residents, providing demographic and laboratory 103 data on participants. This study used datasets from the NHANES 2005-2012 surveys, and 104 applied previously described methods.{Odutayo:2015gs} NHANES was approved by a 105 research ethics committee and conforms to the ethical guidelines of the 1975 Declaration 106 of Helsinki. Informed consent was obtained from each patient. 107  108 Non-pregnant adults aged ≥50 years were included in this study. Age, race and gender 109 were self-reported. The mean of available blood pressure measurements was computed 110 following NHANES guidelines{cdc:2011tg} and in accordance with previous 111 methods{Odutayo:2015gs}. Participants with at least one blood pressure measurement 112 were included and up to 3 blood pressure measurements were available per participant.  113  114 Participants answering “yes” to the following questions were noted as being treated for 115 hypertension: “Because of your high blood pressure/hypertension, have you ever been 116 told to take prescribed medicine?” and “Are you currently taking medication to lower 117 your blood pressure?”. Self-report was used to determine smoking history and identify 118 participants with a family history of premature coronary artery disease (CAD) in any 119 relative <50 years of age. Self report was also used to identify participants with a 120 personal history of acute myocardial infarction (AMI), congestive heart failure (CHF), 121 CAD, angina or stroke. Diabetes was defined as self-reported diabetes or a HbA1c ≥6.5%. 122 Dysglycemia, was defined as prediabetes, impaired fasting glucose, impaired glucose 123  6 tolerance, and diabetes that is controlled with diet only, and was determined based on 124 self-report. 125  126 We examined three treatment thresholds and each was examined sequentially and 127 independent of one another. First, the JNC8 guideline{James:2014ii} was used to 128 determine treatment goals because we sought to demonstrate the extent to which it 129 underestimates the participants that may be eligible for BP lowering. Participants were 130 considered “At target” if they were treated with BP lowering medication(s) and their BP 131 was below target or if they were at target without BP lowering medication. Participants 132 were considered “Eligible for additional BP lowering” if their BP was at or above target. 133 Second, adults with an SBP ≥130 mmHg, were determined to be eligible for additional 134 blood pressure lowering if they were at high cardiovascular risk (≥15% based on the 135 Framingham cardiovascular risk equation) or met the following inclusion criteria 136 specified in SPRINT: age ≥ 75 years, presence of established cardiovascular disease – 137 AMI, CHF, CAD or angina – or chronic kidney disease (CKD), defined as an eGFR 20-138 59 ml/min/1.73m2{SPRINTResearchGroup:2015dw}. Third, we combined the second 139 scenario with an intermediate risk treatment strategy based on the HOPE-3 trial 140 {Lonn:2016fo}. We examined an SBP threshold of 140 mmHg for adults who would be 141 eligible for HOPE-3. Specifically, this included men and women who were ≥55 years and 142 ≥60 years of age respectively, who had at least one of the following characteristics as 143 defined in HOPE-3: current or recent smoking history, low HDL cholesterol, 144 dysglycemia, or a family history of premature CAD {Lonn:2016fo}. We were unable to 145 apply the HOPE-3 inclusion criteria of waist to hip ratio because hip circumference was 146  7 not measured in NHANES. Finally, we retained the treatment thresholds in the JNC8 147 guideline for high risk adults excluded from SPRINT: age < 50 years, diabetes, ≥1 148 gram/day proteinuria, heart failure, stroke and <20 ml/min/1.73m2 eGFR 149 {SPRINTResearchGroup:2015dw}. We also retained the treatment thresholds in the 150 JNC8 guideline for adults excluded from HOPE-3: age < 55 years for men, age < 60 151 years for women, established CVD (defined in our study as angina, CAD, AMI, stroke, 152 CHF), serum creatinine 180μmol/L, or eGFR <45ml/min/1.73m2 {Lonn:2016fo}. This 153 was done to ensure that we were not generalizing the findings of SPRINT and HOPE-3 to 154 large populations that were not studied. 155  156 Absolute 10-year cardiovascular risk was calculated using the Framingham General 157 Cardiovascular Risk Equation {DAgostino:2008kt}. Adults with established CVD – AMI, 158 stroke, or CHF – were considered high risk (≥15%). Using the 2011-2012 US population 159 estimates provided by NHANES, we determined the corresponding number of US adults 160 in each group. The total number of adults aged 50 years and older in 2011-2012 was 161 100,112,910 and we multiplied this by the proportion that were non pregnant, the 162 proportion that had complete BP measurements and finally by any proportions 163 corresponding to the groups of interest in our study (accounting for adults that could not 164 be classified for our study due to missing data). Statistical analyses were conducted using 165 Stata (Version 14).  166  167 RESULTS 168  8 Between 2005 and 2012, NHANES included 7,802 adults who were ≥50 years of age and 169 could be classified for this study. There were 7,314 (94%) adults with 3 BP 170 measurements, 223 (3%) with two BP measurements and 265 (3%) with one BP 171 measurement. Under JNC8 guidelines, 74.8% of adults were at target while 25.2% were 172 eligible for additional BP lowering. If a SBP treatment threshold of 130 mm Hg was used 173 for individuals at high cardiovascular risk, 36.4% of adults (8.1 million additional adults) 174 would be eligible for BP lowering (Table 1). Furthermore, if a SBP treatment threshold of 175 140 mmHg was used for intermediate risk individuals based on the HOPE-3 eligibility 176 criteria, the proportion eligible for blood pressure lowering increased only slightly to 177 36.8% (8.3 million additional adults). 178  179 Based on the JNC8 guidelines, the proportion of patients eligible for BP lowering with 180 prevalent CVD – AMI, stroke and CHF – was 18.5%. With the risk based treatment 181 strategy, 14.2% of adults eligible for BP lowering had prevalent CVD under the high risk 182 strategy and 14.0% of adults had prevalent CVD under the intermediate strategy. 183  184 DISCUSSION 185 If cardiovascular risk is incorporated into current guidelines regarding BP 186 lowering treatment, 8.3 million US adults may warrant additional BP lowering. However, 187 this increase was primarily among adults eligible for SPRINT as opposed to adults 188 eligible for HOPE-3. The proportion of adults eligible for BP lowering with established 189 cardiovascular disease also decreased with the risk based strategies, indicating that an 190 absolute risk strategy would result in an increased emphasis on primary prevention.  191  9  192 There is no consensus on the extent to which the findings generated in SPRINT 193 should be generalized. Some authors have supported a more conservative interpretation 194 of SPRINT and do not advise intensive blood pressure lowering for adults excluded from 195 SPRINT {Chobanian:2015jc}. In contrast, other authors support intensive blood pressure 196 lowering based on absolute risk {Perkovic:2015bb}. In our study, we retained the JNC8 197 guideline treatment thresholds for adults that were excluded from SPRINT because this 198 approach would generate a conservative estimate of the number of adults needing 199 additional blood pressure lowering. If the results of SPRINT are applied more broadly, 200 the number of adults that may be eligible for additional blood pressure lowering would 201 increase. The interpretation of the SPRINT trial in the forthcoming clinical guidelines 202 from the American College of Cardiology and the American Heart Association will 203 therefore have immense public health impact. 204  205 It is also important to recognize that other interventions, beyond that of intensive 206 blood pressure lowering with medications may also serve to decrease the number of 207 adults who are not at target. For instance, in a previous study of a system level changes in 208 hypertension management – which included the creation of a hypertension registry, 209 regular review of hypertension control across primary care settings and provider feedback 210 – investigators demonstrated marked improvement in hypertension control compared to 211 national rates {Jaffe:2013kz}. Implementation of system level changes in hypertension 212 management may therefore reduce the need for additional blood pressure lowering 213 medication as estimated in our study. Other efforts targeted at reducing socioeconomic 214  10 and racial disparities in the initiation and treatment of elevated BP may also reduce the 215 number of individuals who are not at target {Gu:2012iy}. Finally, a robust cost-216 effectiveness analysis of intensive blood pressure lowering has yet to be conducted. 217 Further research, including the pre-specified cost-effectiveness analysis of the SPRINT 218 trial, are required to better inform public health resource allocation.  219  220 There are important limitations to this study. First, for some participants only a 221 single BP measurement was available. Second, diabetes was partially based on self-report, 222 which may under-estimate the prevalence of actual diabetes. Third, BP measurements in 223 SPRINT were taken in an office setting by a fully automated device after patients had 224 been seated quietly without an observer present. This technique is at variance with the 225 measurement techniques that were used in other trails and NHANES. Accordingly, the 226 degree of blood pressure lowering achieved in SPRINT may be 5-10 mmHg lower than in 227 other BP lowering trials {Kjeldsen:2016cm}. If BP is not measured in this way in clinical 228 practice, the target for lowering should be higher than the 120 mmHg achieved in 229 SPRINT. Fourth, we were unable to apply the waist-to-hip ratio eligibility criteria in 230 HOPE-3. This would have led to an underestimate of the number of adults eligible for 231 additional BP lowering. 232  233 Taken together, a large proportion of US adults may be eligible from more 234 intensive BP lowering. This is largely due to adults who meet the eligibility criteria for 235 the SPRINT study. 236 237  11  238 ACKNOWLEDGEMENTS 239 None 240 FUNDING 241 This study was unfunded. 242 DISCLOSURE 243 Nothing to disclose. 244  245 246  12  247  248 References 249 {papers2_bibliography} 250 

Proportion and Characteristics of US Adults Who May Be Eligible From Additional Blood Pressure Lowering Based on Absolute Risk

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