REVIEWS Prehypertension—prevalence, health risks, and management strategies Brent M. Egan and Sean Stevens-Fabry Abstract | Prehypertension (blood pressure 120–139/80–89 mmHg) affects ~25–50% of adults worldwide, and increases the risk of incident hypertension. The relative risk of incident hypertension declines by ~20% with intensive lifestyle intervention, and by 34–66% with single antihypertensive medications. To prevent one case of incident hypertension in adults with prehypertension and a 50% 5‑year risk of hypertension, 10 individuals would need to receive intensive lifestyle intervention, and four to six patients would need to be treated with antihypertensive medication. The relative risk of incident cardiovascular disease (CVD) is greater with ‘stage 2’ (130–139/85–89 mmHg) than ‘stage 1’ (120–129/80–84 mmHg) prehypertension; only stage 2 prehypertension increases cardiovascular mortality. Among individuals with prehypertension, the 10‑year absolute CVD risk for middle-aged adults without diabetes mellitus or CVD is ~10%, and ~40% for middle-aged and older individuals with either or both comorbidities. Antihypertensive medications reduce the relative risk of CVD and death by ~15% in secondary-prevention studies of prehypertension. Data on primary prevention of CVD with pharmacotherapy in prehypertension are lacking. Risk-stratified, patient-centred, comparative-effectiveness research is needed in prehypertension to inform an acceptable, safe, and effective balance of lifestyle and medication interventions to prevent incident hypertension and CVD. Egan, B. M. & Stevens-Fabry, S. Nat. Rev. Cardiol. advance online publication 17 February 2015; doi:10.1038/nrcardio.2015.17
Introduction
Care Coordination Institute and Department of Medicine, University of South Carolina School of Medicine–Greenville, 300 East McBee Avenue, Suite 401, Greenville, SC 29601, USA (B.M.E., S.S.‑F.).
Prehypertension, defined as blood pressure in the range of 120–139/80–89 mmHg, was a controversial term when introduced by the Seventh Joint National Committee on Hypertension (JNC 7) in 2003.1 Blood pressure in the prehypertension range is linked with higher rates of incident hypertension and cardiovascular events than normal, previously considered ‘optimal’, blood pressure of 90 mmHg diastolic on any three visits during the 4‑year trial. The investigators subse quently reported that 52% of the placebo group progressed to hypertension over 4 years when the more conventional
NATURE REVIEWS | CARDIOLOGY
ADVANCE ONLINE PUBLICATION | 3 © 2015 Macmillan Publishers Limited. All rights reserved
REVIEWS Table 2 | Incidence of hypertension in adults with prehypertension Study
Population
Sample size
Mean age (years)
Sex (% female)
BMI (kg/m2)
Prevalence of prehypertension (%)
Follow-up (years)
Incident hypertension (%)
Incident hypertension (%/year)
Gu et al. (2007)45
China
10,525
51.1
49.8
22.1
45.0
8.1
37.1
4.6
Sun et al. (2010)47
China
24,360
48.0
49.5
23.0
70.6
2.3
30.0
13.0
Lüders et al. (2008)
Germany
1,008
62.2
51.6
26.9
100
3.0
42.9
14.3
Vasan et al. (2001)48
Framingham, MA, USA
5,347
52.0
57.3
26.7
54.3
4.0
30.3
7.6
Julius et al. (2006)5
USA
772
48.5
40.1
29.9
100
2.0 4.0
40.4 63.0
20.0 15.8
Conen et al. (2007)49
US Women’s Health Study
39,332
54.7
100
26.0
41.5
2.0
14.7
7.4
Faselis et al. (2012)46
USA veterans
2,303
54.0
0
27.2
100
7.8
31.6
4.1
Selassie et al. (2011)
Southeast USA
18,865
48.5
38.3
30.9
72.4
3.5 7.0
57.3 60.3
16.4 8.6
4
44
Baseline blood pressure 120–139/80–89 mmHg.
definition of two successive visits with blood-pressure readings of ≥140/≥90 mmHg was used.50 In TROPHY,5 moderate-dose renin–angiotensin-receptor blockade reduced the relative risk of incident hypertension by 66% at 2 years compared with placebo, and by ~15% at 4 years (2 years after medication was discontinued). In the PHARAO study 4 in adults with stage 2 prehyper tension, 43% of the group randomly allocated to placebo developed hypertension in 3 years. The incidence rates in the PHARAO,4 TROPHY,5 and Framingham39 studies are of a similar magnitude when the analysis is restricted to individuals with stage 2 prehypertension at baseline. In PHARAO,4 monotherapy with a low-dose angiotensinconverting-enzyme inhibitor reduced the relative risk of incident hypertension by 34% over 3 years compared with placebo. In contrast to annual incident hypertension rates of ~8–20% reported in studies lasting 2–4 years, annual ized incident hypertension is 4–9% in studies with 7–8 years of follow-up (Table 2). In one study, 57.3% of the original nonhypertensive cohort were hypertensive at 3.5 years, and 60.3% were hypertensive at 7 years.44 Therefore, the original cohort contains at least two groups of individuals—one group of individuals at high risk of transition to incident hypertension within 3 years, and another group at substantially lower risk of transition, even after 7 years of follow-up. Ethnic differences in rates of incident hyperten sion might have important implications for reduc ing the disparity in the prevalence of hypertension and related cardiovascular and renal complications. Specifically, prehypertension is slightly less prevalent in African-American than white individuals (30.4% versus 31.2%),6 whereas hypertension is ~40% more prevalent in African-American than white individuals. 1 These observations raise the possibility that transition from prehypertension to hypertension is faster in black than white individuals. If so, interventions that reduce this ethnic disparity in progression from prehypertension to hypertension in susceptible African-American patients
could, over time, reduce the prevalence of hypertension and related clinical complications. To address this important topic, rates of progression from prehypertension to hypertension were assessed in individuals receiving care at diverse clinical sites in southeast USA that were participating in the Outpatient Quality Improvement Network. 44 A total of 18,865 individuals without hypertension (30.4% black, 69.6% white) and aged 18–85 years met the study inclusion criteria. Electronic health record system data were used to assess days elapsing from study entry to a diagnosis of hypertension, mainly defined as a clinical diagnosis of hypertension or blood pressure ≥140 mmHg systolic and/or ≥90 mmHg diastolic on two consecutive visits within a maximum observation period of 2,550 days. Cox proportional hazards regression modelling was used to examine progression to hypertension as a func tion of ethnicity, when controlling for age, sex, baseline systolic and diastolic blood pressure, BMI, and the pres ence of diabetes or chronic kidney disease. The adjusted median conversion time when 50% became hyperten sive was 365 days earlier for black than white individuals (626 days, 95% CI 591–662 days versus 991 days, 95% CI 950–1,026 days; P
Introduction
Care Coordination Institute and Department of Medicine, University of South Carolina School of Medicine–Greenville, 300 East McBee Avenue, Suite 401, Greenville, SC 29601, USA (B.M.E., S.S.‑F.).
Prehypertension, defined as blood pressure in the range of 120–139/80–89 mmHg, was a controversial term when introduced by the Seventh Joint National Committee on Hypertension (JNC 7) in 2003.1 Blood pressure in the prehypertension range is linked with higher rates of incident hypertension and cardiovascular events than normal, previously considered ‘optimal’, blood pressure of 90 mmHg diastolic on any three visits during the 4‑year trial. The investigators subse quently reported that 52% of the placebo group progressed to hypertension over 4 years when the more conventional
NATURE REVIEWS | CARDIOLOGY
ADVANCE ONLINE PUBLICATION | 3 © 2015 Macmillan Publishers Limited. All rights reserved
REVIEWS Table 2 | Incidence of hypertension in adults with prehypertension Study
Population
Sample size
Mean age (years)
Sex (% female)
BMI (kg/m2)
Prevalence of prehypertension (%)
Follow-up (years)
Incident hypertension (%)
Incident hypertension (%/year)
Gu et al. (2007)45
China
10,525
51.1
49.8
22.1
45.0
8.1
37.1
4.6
Sun et al. (2010)47
China
24,360
48.0
49.5
23.0
70.6
2.3
30.0
13.0
Lüders et al. (2008)
Germany
1,008
62.2
51.6
26.9
100
3.0
42.9
14.3
Vasan et al. (2001)48
Framingham, MA, USA
5,347
52.0
57.3
26.7
54.3
4.0
30.3
7.6
Julius et al. (2006)5
USA
772
48.5
40.1
29.9
100
2.0 4.0
40.4 63.0
20.0 15.8
Conen et al. (2007)49
US Women’s Health Study
39,332
54.7
100
26.0
41.5
2.0
14.7
7.4
Faselis et al. (2012)46
USA veterans
2,303
54.0
0
27.2
100
7.8
31.6
4.1
Selassie et al. (2011)
Southeast USA
18,865
48.5
38.3
30.9
72.4
3.5 7.0
57.3 60.3
16.4 8.6
4
44
Baseline blood pressure 120–139/80–89 mmHg.
definition of two successive visits with blood-pressure readings of ≥140/≥90 mmHg was used.50 In TROPHY,5 moderate-dose renin–angiotensin-receptor blockade reduced the relative risk of incident hypertension by 66% at 2 years compared with placebo, and by ~15% at 4 years (2 years after medication was discontinued). In the PHARAO study 4 in adults with stage 2 prehyper tension, 43% of the group randomly allocated to placebo developed hypertension in 3 years. The incidence rates in the PHARAO,4 TROPHY,5 and Framingham39 studies are of a similar magnitude when the analysis is restricted to individuals with stage 2 prehypertension at baseline. In PHARAO,4 monotherapy with a low-dose angiotensinconverting-enzyme inhibitor reduced the relative risk of incident hypertension by 34% over 3 years compared with placebo. In contrast to annual incident hypertension rates of ~8–20% reported in studies lasting 2–4 years, annual ized incident hypertension is 4–9% in studies with 7–8 years of follow-up (Table 2). In one study, 57.3% of the original nonhypertensive cohort were hypertensive at 3.5 years, and 60.3% were hypertensive at 7 years.44 Therefore, the original cohort contains at least two groups of individuals—one group of individuals at high risk of transition to incident hypertension within 3 years, and another group at substantially lower risk of transition, even after 7 years of follow-up. Ethnic differences in rates of incident hyperten sion might have important implications for reduc ing the disparity in the prevalence of hypertension and related cardiovascular and renal complications. Specifically, prehypertension is slightly less prevalent in African-American than white individuals (30.4% versus 31.2%),6 whereas hypertension is ~40% more prevalent in African-American than white individuals. 1 These observations raise the possibility that transition from prehypertension to hypertension is faster in black than white individuals. If so, interventions that reduce this ethnic disparity in progression from prehypertension to hypertension in susceptible African-American patients
could, over time, reduce the prevalence of hypertension and related clinical complications. To address this important topic, rates of progression from prehypertension to hypertension were assessed in individuals receiving care at diverse clinical sites in southeast USA that were participating in the Outpatient Quality Improvement Network. 44 A total of 18,865 individuals without hypertension (30.4% black, 69.6% white) and aged 18–85 years met the study inclusion criteria. Electronic health record system data were used to assess days elapsing from study entry to a diagnosis of hypertension, mainly defined as a clinical diagnosis of hypertension or blood pressure ≥140 mmHg systolic and/or ≥90 mmHg diastolic on two consecutive visits within a maximum observation period of 2,550 days. Cox proportional hazards regression modelling was used to examine progression to hypertension as a func tion of ethnicity, when controlling for age, sex, baseline systolic and diastolic blood pressure, BMI, and the pres ence of diabetes or chronic kidney disease. The adjusted median conversion time when 50% became hyperten sive was 365 days earlier for black than white individuals (626 days, 95% CI 591–662 days versus 991 days, 95% CI 950–1,026 days; P
