Elevated blood pressure (BP) and the risk of stroke have been recognized as a strong association since the 1920s . Numerous clinical trials have described the clear benefits of lowering BPs of hypertensive individuals in an effort to reduce stroke . The evidence is strong, continuous, graded, consistent, independent, predictive, and causatively significant for those with and without coronary heart disease [3,4]. These results and data analyses form the basis for the development of clinical guidelines for the management of high BP.
POPULATION RISK OF STROKE BECAUSE OF ELEVATED BLOOD PRESSURES
Epidemiological studies have shown elevated BP is the most important determinant of the risk of stroke. The linear risk is relatively low levels of SBP and DBP with significant increases for all age groups . Risk factors for high BP, such as obesity, increased waist circumference, higher alcohol intake, and greater sodium intake, are also associated with increased risks for stroke .
Estimates from the National Health and Nutrition Examination Survey (NHANES) identify 64 million or more Americans with high BP requiring monitoring and treatment [7,8]. Further, the global prevalence estimates of 1 billion individuals, with an estimated 7.1 million deaths per year may be attributable to hypertension . This high and increasing prevalence and the clinical ability to reduce elevated BPs resulting in substantial benefits of hypertension control have led federal, professional, and voluntary agencies to develop education programs for the healthcare personnel regarding the effective management of hypertension. Significant reductions of the population burden of hypertension and stroke have resulted from the achievement in the past in meeting the goals of these programs. The characteristics of hypertensive patients have improved with more than 90% of the population aware of the relationship of high BP and stroke, nearly three-fourths of the hypertensive population being treated, and over half of those treated for high BP are controlled to below 140/90 mmHg . As presented in Table 1, the mean SBP (SBP) for the U.S. adult population declined from 131 mmHg in 1960 to 122 mmHg in 2008. Between 1960 and 1991, median SBP for individuals aged 60–74 declined by approximately 16 mmHg [11▪,12]. These population changes in reduced BP levels have been associated with the large reductions in stroke mortality.
The benefits of lowering marked hypertension have been shown in the epidemiologic and observational studies demonstrating stroke risks with increasing BP levels. In a meta-analysis of 61 prospective, observational studies conducted by Lewington et al. and including one million adults with no previous vascular disease at baseline found that between the age of 40 and 69 years, each incremental rise of 20 mmHg SBP and 10 mmHg DBP was associated with a two-fold increase in death rates because of stroke. This effect is seen in all decades of life.
The increase in the incidence and prevalence of hypertension is in part attributed to the age-related rise in SBP . Further, results from the Framingham Heart Study determined the lifetime risk of hypertension to be approximately 90% for men and women who were nonhypertensive at 55 or 65 years and survived to age 80–85 . Even after adjusting for competing mortality, the remaining lifetime risks of hypertension were 86–90% in women and 81–83% in men . These lifetime estimates are important components in the assessment of the impact of BP reduction for stroke mortality declines . The increase of BP to hypertensive levels with age is evident by the patterns and trends indicating that the 4-year rates of progression to hypertension are 50% for those 65 years and older with BP in the 130–139/85–89 mmHg range and 26% for those with BP in the 120–129/80–84 mmHg range.
Cohort studies have demonstrated the significant increased attributable risks associated with elevated BP and stroke [17,18]. These risk estimates are consistent for all age–race–sex groups of the population with significant population attributable risk for elevated BPs and stroke mortality. The relationship between BP and risk of stroke events is demonstrated over time, continuous, consistent, and independent of other risk factors. The linear relationship holds true for all demographics, indicating the higher the BP the greater the risk of stroke mortality.
STROKE RISK REDUCTION FROM RANDOMIZED CONTROLLED TRIALS
Clinical trials have demonstrated that control of isolated systolic hypertension reduces stroke mortality . Results from the Hypertension Detection and Follow-up Program (HDFP) showed 4.7 mmHg reduced stroke mortality by 17.6% . Numerous other trials have provided evidence of hypertension treatment with BP reduction and subsequent reduced stroke risks. The trials include placebo, comparison and efficacy designs with similar results indicating a benefit of BP reduction and stroke risks. The studies also included different ages, races, and both sexes as well as different time-periods with consistent findings of stroke risk reduction with hypertension treatment. Another overview of evidence from observational epidemiologic studies and randomized controlled trials determined an average reduction of 12–13 mmHg in SBP over 4 years of follow-up was associated with a 37% in stroke mortality . Hypertensive patients with diabetes were found to have lower stroke risks with aggressive BP treatment.
PREVIOUS HYPERTENSION TREATMENT GUIDELINES
The results of the observational epidemiologic studies and randomized controlled trials have contributed to the development of hypertension treatment guidelines. Since 1977, the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC) has recognized the high impact of elevated BPs and published guidelines on the diagnosis, prevention, and management of hypertension [21–28]. The treatment guidelines have included recommendations focused on the reduction of hypertension-related conditions including stroke. The guidelines have evolved providing detailed strategies focused on the benefits of treating to lower the BP levels, as well as study results which differentiate the effectiveness and efficacy of the different classes of treatment. A major contribution of the JNC guidelines is the definition of hypertension and BP treatment goals. While the first two reports did not designate specific SBP values, later reports identified levels of BP for the initiation of therapy and target BP goals, as well as recommended treatment regimens to achieve these levels. From the first report through JNC 7, the BP levels for treatment initiation and target goal BP have typically been lowered with each version. Specifically, the reports have emphasized the SBP level for the clinical management with recognition of 130 mmHg as prehypertension in JNC 7. In addition, these treatment guidelines recognized hypertensive patients with diabetes and kidney disease with increased cardiovascular disease risks and recommended aggressive treatment with 130 mmHg. As seen in Table 1, population average SBP levels are lower with the release of the subsequent JNC guideline version. The lower SBP levels are consistent with the predicted lower stroke mortality rates. Thus, the guidelines recommendations prepared for the clinical management would appear to also have implications for public health hypertension control efforts.
The implementation of the guidelines to address the population at risks is designed to impact the disease risk including stroke mortality [29▪]. While the development process for the national hypertension treatment guidelines have been well established and described, the science attached to the implementation of guidelines is relatively new. Effectiveness of a highly evidence-based guideline, such as the 8th Joint National Committee recommendations on the treatment of high BP, is highly dependent on the successful translation into clinical practice. Such implementation of the recommendations is dependent on multiple factors. First, the recommendation statements must be stated and reported in a clear manner with executable guideline language. Further, an audit and feedback system should be attached to the education of practitioners charged with carrying out the guidelines. Likewise, the implementation should include a team-based care delivery approach with various disciplines on the team. The credibility of BP measurement represents an essential component of the successful implementation. A critical assessment is the measurement of therapeutic inertia and medication adherence. The successful implementation of hypertension guidelines, including the JNC guidelines, is a critical requirement for the effectiveness on stroke prevention. Further research is needed to assess the efficacy and cost-effectiveness of various implementation tools and strategies.
Significant improvements in cardiovascular and stroke outcomes may be associated with the successful implementation of hypertension treatment guidelines [30▪▪]. Bertoia and colleagues have assessed the cardiovascular disease prevention implications of the American Heart Association scientific statement for the treatment of hypertension. The report was released in 2007 and was based on the clinical trial evidence and expert opinion. These recommendations promoted an aggressive control of BP (130/80 mmHg) among individuals with high risk from coronary artery disease, diabetes mellitus, chronic kidney disease, coronary artery disease or coronary artery disease risk equivalent, and a 10-year Framingham risk score of 10%. The 2011 American College of Cardiology Foundation/American Heart Association (AHA) hypertension guidelines for the elderly, also included in this assessment, recommended a less aggressive approach of 145/90 mmHg in those over the age of 80 years. Bertoia et al. estimated the burden of uncontrolled hypertension for individuals with coronary artery disease using both the 2007 AHA and the 2011 American College of Cardiology Foundation/AHA hypertension guidelines and based impact on a cross-sectional analysis of NHANES 2005–2008 participants. The profile of this study population included 10 198 adults aged 18–85 years. Using the 2011 American College of Cardiology Foundation/AHA hypertension guidelines (140/90 mmHg), 72 million Americans (35%) were estimated to have hypertension. Considering the 2007 AHA guidelines, an additional 7 million American adults (5%) have elevated BP requiring treatment for a total of 79 million adults (40%). It was determined that although individuals with a higher risk for coronary artery disease are more likely to be aware of their hypertension and to be taking antihypertension medication, they are less likely to have their high BP under control. This higher rate of uncontrolled hypertension would be associated with a higher risk of stroke. These results emphasize the need for successful implementation of the hypertension treatment guidelines.
STROKE AS A CARDIOVASCULAR RISK EQUIVALENT
Complicating the assessment of hypertension guidelines and stroke prevention is the recognition of stroke as a cardiovascular risk equivalent [31▪▪]. The evidence from observational epidemiologic studies and randomized clinical trials were assessed to determine the appropriateness of the inclusion of stroke in cardiovascular risk assessment instruments and models. The results determined that patients with atherosclerotic stroke should be included among those deemed to be at high risk (20% over 10 years) of further atherosclerotic coronary events. Thus, for prevention strategies, ischemic stroke should be included among cardiovascular disease outcomes in absolute risk assessment algorithms. The inclusion of atherosclerotic ischemic stroke as a high-risk condition and the inclusion of ischemic stroke more broadly as an outcome have significant implications for the prevention of cardiovascular disease including hypertension management as the number of patients considered to be at high risk would grow substantially. Further, the clinical management of high BP should consider whether hypertensive individuals with a history of ischemic stroke should be treated with greater aggressive therapy.
DEVELOPMENT OF NEW GUIDELINES
High BP treatment and control is a key component of the current stroke prevention guidelines in addition to the hypertension guidelines [32▪]. In addition to the trials and studies previously described, several recent and current trials provide additional data on the benefits of treatment and control of hypertension in reducing recurrent stroke risks. The perindopril protection against recurrent stroke study (PROGRESS) showed a significant reduction in stroke risks with combination hypertension treatment of an angiotensin-converting-enzyme (ACE) inhibitor and a diuretic among both hypertensive and nonhypertensive individuals with a history of stroke or transient ischemic attack . In contrast, the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) Study found treatment with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke . The Secondary Prevention of Small Subcortical Strokes (SPS3) trial showed no significant reduction in recurrent stroke among patients with recent lacunar strokes with the addition of clopidogrel to aspirin . The impact on the results from the SPS3 trial with hypertension control will be assessed in future analyses. Likewise, the Systolic Blood Pressure Intervention Trial (SPRINT) is an ongoing double-arm, multicenter, randomized clinical trial designed to assess the treatment of hypertension aimed at reducing SBP to a lower goal than currently recommended with the reduction of cardiovascular disease and stroke risks (http://clinicaltrials.gov/ct2/show/NCT01206062).
The Institute of Medicine has indicated that clinical guidelines should be based on high levels of evidence . However, some earlier guidelines and recommendations have been assessed to be based on relatively lower levels of evidence . Thus, future recommendations, including JNC, should be developed and based on high-quality evidence in order to improve trust from providers . The basis of the new guidelines on strong evidence is critical for the effective impact on the population burden of uncontrolled hypertension and stroke risks [37,38▪]. Likewise, major population and clinical strategies are being developed and implemented to reduce stroke risks, and these interventions must be based on high levels of evidence for greatest levels of effect [39,40▪▪,41].
Clearly hypertension is a clear and significant independent risk factor for stroke. It appears that guidelines and recommendations for the treatment and management of high BP have made an impact on population BP levels and subsequent stroke risks. With the development of strict evidence-based guidelines, clinical recommendations may be highly detailed for specific strategies. However, the full potential of the guidelines’ impact is dependent on the successful implementation and translation into clinical practice. Thus, it will be expected that the future guidelines will have additional impact and effects on stroke risk reduction.
Conflicts of interest
No conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 103).
1. Society of Actuaries: build and blood pressure study. Vol. 1. Chicago, IL: Society of Actuaries; 1959.
2. Freis ED. The role of hypertension. Am J Hypertens 1960; 50:11–13.
3. Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med 1993; 153:598–615.
4. Flack JM, Neaton J, Grimm R Jr, et al. Blood pressure and mortality among men with prior myocardial infarction. Multiple Risk Factor Intervention Trial Research Group. Circulation 1995; 92:2437–2445.
5. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360:1903–1913.
6. Kuller LH. Epidemiology and prevention of stroke
, now and in the future. Epidemiol Rev 2000; 22:14–17.
7. Burt VL, Whelton P, Roccella EJ, et al. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension 1995; 25:305–313.
8. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA 2003; 290:199–206.
9. World Health Organization. The World Health Report 2002: reducing risks, promoting healthy life. Geneva, Switzerland. Available at http://www.who.int/whr/2002/
. [Accessed 23 July 2012].
10. Roccella EJ. The National High Blood Pressure Education Program. In: Oparil S, Weber M, editors. Hypertension: a companion to Brenner and Rector's the kidney. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2005.
11▪. Wright JD, Hughes JP, Ostchega Y. Mean systolic and diastolic blood pressure in adults aged 18 and over in the United States, 2001–2008. National Health Statistics Reports; no. 35. Hyattsville, MD: National Center for Health Statistics; 2011.
This is the most recent NHANES SBP data.
12. Yoon SS, Ostchega Y, Louis T. Recent trends in the prevalence of high blood pressure and its treatment and control, 1999–2008. NCHS Data Brief, no. 48. Hyattsville, MD: National Center for Health Statistics; 2010.
13. Franklin SS, Gustin WT, Wong ND, et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation 1997; 96:308–315.
14. Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: the Framingham Heart Study. JAMA 2002; 287:1003–1010.
15. Lloyd-Jones DM, Hong Y, Labarthe D, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's Strategic Impact Goal through 2020 and beyond. Circulation 2010; 121:586–613.
16. Vasan RS, Larson MG, Leip EP, et al. Assessment of frequency of progression to hypertension in nonhypertensive participants in the Framingham Heart Study: a cohort study. Lancet 2001; 358:1682–1686.
17. Lackland DT, Keil JE, Gazes PC, et al. Outcomes of black and white hypertensive individuals after 30 years of follow-up. Clin Exp Hypertens 1995; 17:1091–1105.
18. Gazes PC, Lackland DT, Mountford WK, et al. Comparison of cardiovascular risk factors for high brachial pulse pressure in blacks versus whites (Charleston Heart Study, Evans County Study, NHANES I and II Studies). Am J Cardiol 2008; 102:1514–1517.
19. Ogden LG, He J, Lydick E, Whelton PK. Long-term absolute benefit of lowering blood pressure in hypertensive patients according to the JNC VI risk stratification. Hypertension 2000; 35:539–543.
20. Lackland DT, Egan BM, Mountford WK, et al. Thirty-year survival for black and white hypertensive individuals in the Evans County Heart Study and the hypertension detection and follow-up program. J Am Soc Hypertens 2008; 2:448–454.
21. He J, Whelton PF. Elevated systolic blood pressure and risk of cardiovascular and renal disease: overview of evidence from observational epidemiologic studies and randomized controlled trials. Am Heart J 1999; 138:S211–S219.
22. Report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure. A cooperative study. JAMA 1977; 237:255–261.
23. The 1980 report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1980; 140:1280–1285.
24. The 1988 report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure. Arch Intern Med1988; 148:1023–1038.
25. The 1984 report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1984; 144:1045–1057.
26. The fifth report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure (JNC V). Arch Intern Med 1993; 153:154–183.
27. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157:2413–2446.
28. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289:2560–2572.
29▪. Handler J, Lackland DT. Translation of hypertension treatment guidelines into practice: a review of implementation. J Am Soc Hypertens 2011; 5:197–207.
This study describes the critical importance of translating hypertension guidelines into practice in order to achieve outcome prevention including stroke.
30▪▪. Bertoia ML, Waring ME, Gupta PS, et al. Implications of new hypertension guidelines in the United States. Hypertension 2012; 60:639–644.
This is a new study that addresses the implications of hypertension guidelines on the population health. These implications are relevant to the JNC and other current hypertension guidelines.
31▪▪. Lackland DT, Elkind MS, D’Agostino R Sr, et al. Inclusion of stroke
in cardiovascular risk prediction instruments: a statement for healthcare professionals from the American Heart Association/American Stroke
This study describes the evidence to include stroke as a cardiovascular risk equivalent in models and risk prediction instruments. This study has implications to the treatment of hypertension in individuals with stroke.
32▪. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke
in patients with stroke
or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke
This is an important study that includes the current stroke prevention guidelines. While the guidelines focus on stroke prevention, hypertension treatment and control is a major focus.
33. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke
or transient ischaemic attack. Lancet 2001; 358:1033–1041.
34. Yusuf S, Diener HC, Sacco RL, et al.
, for the PRoFESS Study Group. Telmisartan to prevent recurrent stroke
and cardiovascular events. N Engl J Med 2008; 359:1225–1237.
35. The SPS3 Investigators. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke
. N Engl J Med 2012; 367:817–825.
36. Graham R, Mancher M, Wolman DM, et al.
, editors. Clinical practice guidelines we can trust. Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Institute of Medicine; 2011
37. Tricoci P, Allen JM, Kramer JM, et al. Scientific evidence underlying the ACC/AHA clinical guidelines. JAMA 2009; 301:831–841.
38▪. Fryar CD, Chen T, Li X. Prevalence of uncontrolled risk factors for cardiovascular disease: United States, 1999–2010. NCHS data brief. no. 103. Hyattsville, MD: National Center for Health Statistics; 2012.
This study is the more recent data from NHANES and described the public health burden of uncontrolled hypertension in the United States. CDC.
39. Centers for Disease Control and Prevention. Million hearts: strategies to reduce the prevalence of leading disease risk factors – United States, 2011. MMWR Morb Mortal Wkly Rep 2011; 60:1248–1251.
40▪▪. Tomaselli GF, Harty MB, Horton K, Schoeberl M. The American Heart Association and the Million Hearts Initiative: a presidential advisory from the American Heart Association. Circulation 2011; 124:1795–1799.
This study described a major population-based initiative for stroke prevention. Treatment of hypertension is a major component of this effort.
41. Sacco RL, Frieden TR, Blakeman DE, et al. What the million heart initiative means for stroke
. A presidential advisory from the American Heart Association/American Stroke