2. • Traube (Berlin, 1856) “High Blood
Pressure Is Needed”
– Elevated arterial pressure
necessary
• Overcome resistance of
thickened arteries.
• Kidney.function
• Page (Cleveland, 1934) “High
Blood Pressure Is NOT
Necessary”
– Reduced HBP without decreased
kidney function
Richard Bright, M.D.F.R.S.
1789-1858
Father of Nephrology
3.
4.
5. Office BP Measurement
Use auscultatory method with a properly calibrated and validated
instrument.
Patient should be seated quietly for 5 minutes in a chair
(not on an exam table), feet on the floor, and arm supported at heart
level.
Appropriate-sized cuff should be used to ensure accuracy.
At least two measurements should be made.
Clinicians should provide to patients, verbally and in writing, specific BP
numbers and BP goals.
6. Note that Blood Pressure is not associated with symptoms
except at the extremes of the distirbution
acsweb.fmarion.edu/Pryor/bellcurve.htm
7.
8.
9. JNCVII Hypertension Classification
Normal <120 and <80
Prehypertension 120–139 or 80–89
Stage 1 HBP 140–159 or 90–99
Stage 2 HBP >160 or >100
BP
Classification
SBP
mmHg
DBP
mmHg
10.
11. Identifiable
Causes of Hypertension
Monogenic causes
Sleep apnea
Drug-induced or related causes
Chronic kidney disease
Primary aldosteronism
Renovascular disease
Cushing’s syndrome
Pheochromocytoma
Coarctation of the aorta
Thyroid or parathyroid disease
13. Hypertension-related QTLs across the genome, as reported in the literature.
Red bars represent the locations of QTL peaks. Bars shown beneath
chromosomes represent QTLs on the designated chromosome for which no
marker location has been reported Cowley Nature Reviews Genetics 7, 829–840 (November 2006)
14. Risk factors for “primary” hypertension
• Genetic predisposition.
• African American race.
• Geographic location
• Male gender.
• Increasing age.
• Nutrition.
– Sodium (salt) sensitivity
– Obesity and overweight
• Sedentary or inactive lifestyle.
• Heavy alcohol consumption.
• Medication.
– Oral contraceptives
– NSAIDs
– Cold remedies/diet pills
– Tricyclic antidepressants/Monoamine oxidase inhibitors
15. Landmark Clinical Trials
Hypertension Treatment and Cardiovascular
Disease Outcomes
1967 – VA Cooperative Study on DBP 115-129
1970 – VA Cooperative Study on DBP 90-114
1979 – HDFP
1980 – Australian Trial, Oslo Trial
1985 – MRC I, EWPHE
1991 – SHEP, STOP-Hypertension
1992 – MRC II in the elderly
1997 – Syst-Eur
2002 – LIFE
2002 – ALLHAT
16. Veterans Administration, 1967
Veterans Administration, 1970
Hypertension Stroke Study, 1974
USPHS Study, 1977
EWPHE Study, 1985
Coope and Warrender, 1986
SHEP Study, 1991
STOP-Hypertension Study, 1991
MRC Study, 1992
Syst-Eur Study, 1997
Total
Relative Risk for Coronary Heart Disease
Odds ratios and
95% confidence intervals
0 0.5 1 1.5 2
0.79 (0.69 to 0.90)
He J, et al. Am Heart J. 1999; 138:211-
219
Active treatment
BETTER WORSE
17. Veterans Administration, 1967
Veterans Administration, 1970
Hypertension Stroke Study, 1974
USPHS Study, 1977
EWPHE Study, 1985
Coope and Warrender, 1986
SHEP Study, 1991
STOP-Hypertension Study, 1991
MRC Study, 1992
Syst-Eur Study, 1997
Total
Relative Risk for Stroke
0 0.5 1 1.5 2
0.63 (0.55 to 0.72)
Odds ratios and
95% confidence intervals
He J, et al. Am Heart J. 1999; 138:211-219
Active treatment
BETTER WORSE
18. Algorithm for Treatment of
Hypertension
Not at Goal Blood Pressure (<140/90 mmHg)
(<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Drug(s) for the compelling
indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, CCB)
as needed.
With Compelling
Indications
Lifestyle Modifications
Stage 2 Hypertension
(SBP >160 or DBP >100 mmHg)
2-drug combination for most
(usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension
(SBP 140–159 or DBP 90–99 mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
Without Compelling
Indications
Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
19. Proposed Healthy People 2020 Goals
HDS HP2020–4: Increase the proportion of adults with high blood pressure
whose blood
pressure is under control.
Data Source: National Health and Nutrition Examination Survey (NHANES), CDC,
NCHS.
Action: Retained Healthy People 2010 objective 12-10.
HDS HP2020–5: Increase the proportion of adults who have had their blood
pressure
measured within the preceding 2 years and can state whether their blood
pressure was normal or high.
Data Source: National Health Interview Survey (NHIS), CDC, NCHS.
Action: Retained Healthy People 2010 objective 12-12.
20. BP Control Rates US: National Health and
Nutrition Examination Survey
Trends in awareness, treatment, and control of high
blood pressure in adults ages 18–74
%
II
1976–80
II
(Phase 1)
1988–91
II
(Phase 2)
1991–94 1999–2000
Awareness 51 73 68 70
Treatment 31 55 54 59
Control 10 29 27 34
Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6.
Editor's Notes
It is important to recognize that many chronic diseases which have “emerged” in modern populations were recognized as diseases or disease related conditions before they became major causes of morbidity and mortality.
This slide illustrates quotes from earlier scientists that illustrate 1) the awareness of high blood pressure and 2) the disagreement as to the clinical relevance of elevated blood pressure This ambiguity was resolved by multiple observational studies and clinical trials.
The essence of science is measurement of study related variables. The process of measuring an attribute is characterized by validity and reliability (see quality of life lecture for definitions).
This slide illustrates blood pressure (BP) measurement in a typical clinical setting. BP is the hydraulic pressure generated by the contraction of the heart that propels blood through the circulatory system against variable resistance to blood flow generated by contraction of the small muscular arteries and non-dynamic resistance generated by the structural characteristics of the circulatory system.
BP=Cardiac output X Resistance
Careful BP measurement in epidemiology studies is essential to avoid misclassification.
There is substantial temporal variation in an individual’s BP. This slide illustrates temporal variation on different time scales:
Daily (upper left). Note the substantial variation in hour-to-hour BP values.
Minute to minute (lower left). Note the substantial variation in minute-to-minute BP values.
Monthly (seasonal)
Over the life course
The daily measurement variation illustrates the importance of time of day and minute-to-minute variability in BP measurement when estimating
BP as a study variable. These concerns should be incorporated into the study’s BP measurement protocol to minimize measurement error and
misclassification.
This is a simple example of a BP measurement protocol
How do we define a BP measurement as “high” or “low”?
This issue is illustrated in the population distribution of BP which, like many variables measured on a continuous scale in large populations, approaches a normal distribution. This tendency is an expression of the central limit theorem of probability that states that as the sample size (n) grows, the distribution becomes more like the normal distribution.
This means that there are no obvious cut points to distinguish a high (or low) BP sub-population in the distribution.
The definition of high blood pressure thus must rest on empiric grounds defined by an association between the measure and risk.
This slide illustrates the associations observed between mean diastolic BP (DBP) and stroke risk. What mean DBP defines a point which is associated with increased stroke and coronary heart disease risk? How might you use this and similar information to define a high DBP?
Ditto for end-stage kidney disease.
The DBP levels used to define the stages of hypertension risk are not important; the graded increase (dose response) carries the message.
Clinicians use stratification based on clinical information to classify risk (diagnostic decision making) and guide therapeutic decision making. Current guidelines recommend lifestyle modification for pre-hypertension and antihypertensive therapy for Stage 1 and 2 HBP.
Compare the cut-points from the current risk stratification of BP to the preceding slide. How do they differ?
Increasing prevalence of hypertension is common across world populations. This slide illustrates the application of areal (geographic) display of prevalence data. This type of ‘Place’ data must be interpreted with its ecologic nature in mind
Note the variability across regions. What sorts of hypotheses do these data engender?
Studies of regions and populations with high or low prevalence of hypertension have been very productive of testable hypotheses.
Hypertension is typical of most chronic diseases and their risk factors in that they are mutifactorial in causation. This list includes many of the recognized “causes” of elevated BP which, in some cases, lead to specific interventions.
Single gene disorders are highly informative with respect to understanding disease mechanisms and targeting therapy. However, they account for lees than 1% of the hypertensive phenotype.
There remains considerable interest in the genetic predisposition to high blood pressure. This list includes the best studied and understood single gene disorders associated with elevated blood pressure. Note worthy is the recognition that none of these genes results in a simple phenotype characterized solely by increased blood pressure.
This slide illustrates the more common genetic background for chronic diseases. The association between BP level and multiple allelic variations and single nucleotide polymorphisms in non-coding regions of the genome characterize a complex trait.
The variation in BP explained by any single polymorphism is very small and the relationship between the SNP and biological mechanisms is usually not yet worked out.
These two examples of “genetic predisposition” illustrate the continuing interest in the environmental aspects of person, place and time in the “gene-environment” understanding of phenotype and disease
Examples of environment. Note that gender, race, age, and geography (measures of person, place and time) are complex and generative of hypotheses rather than explanatory. For example, think of the variety of biological, social, environmental, and SES factors associated with gender.
On the other hand, some of these risk factors are modifiable (nutrition, activity, alcohol consumption and medication exposure) and this knowledge is incorporated into clinical practice guidelines.
What might be the utility of including the two categories in a single inventory of risk factors? Does this differ from the Framingham Risk factors for CAD?
To recapitulate: elevated BP is a risk factors for cardiovascular (stroke and coronary heart disease) and kidney disease. It is a complex trait. Epidemiologic and clinical trail evidence has been used to develop risk stratification cutpoints for increased risk from elevated blood pressure.
Does modification of BP reduce risk?
The trials listed above are illustrative of and, arguably the most important, of a continuing series of randomized clinical trials to address this question. The dates illustrate the temp of the research to address the clinical utility of amodification of a particular risk factor. Not easy work.
Relative Risk for Coronary Heart Disease
This meta-analysis examines the relative risk for coronary heart disease (CHD) events in a variety of placebo control clinical trials. Although individual trials differed in the magnitude of risk reduction, the overall result was a 21% lower risk in total CHD in patients receiving active therapy compared with placebo (95% confidence intervals [CI] 10% to 31%; P&lt;0.001). Fatal CHD was reduced 27% (95% CI 13% to 38%; P&lt;0.001). Overall, 412 CHD events occurred in participants assigned to active treatment and 520 in those assigned to placebo. It should be noted, however, that among these 10 trials, the reduction in risk was only statistically significant for the SHEP study, in which CHD was reduced by 28% (95% CI 6% to 44%).
References:
He J, Whelton PK. 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 (3 Pt 2):211-9.
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202 (11):1028-34.
Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970; 213 (7):1143-52.
Effect of antihypertensive treatment on stroke recurrence. Hypertension-Stroke Cooperative Study Group. JAMA 1974; 229 (4):409-18.
Amery A, Birkenhager W, Brixko P et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet 1985; 1 (8442):1349-54.
Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. Br Med J (Clin Res Ed) 1986; 293 (6555):1145-51.
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24):3255-64.
Dahlof B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991; 338 (8778):1281-5.
Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992; 304 (6824):405-12.
Staessen JA, Fagard R, Thijs L et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997; 350 (9080):757-64.
Relative Risk for Stroke
A similar analysis of stroke risk in this meta-analysis demonstrates a 37% lower risk of stroke in patients receiving active therapy vs. placebo (95% confidence interval [CI] 28% to 45%; P&lt;0.001). Overall, there were 385 strokes in participants allocated to active treatment, and 596 in those assigned to placebo. Out of the 10 trials, the reduction in stroke was statistically significant in 6 of them.
References:
He J, Whelton PK. 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 (3 Pt 2):211-9.
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202 (11):1028-34.
Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970; 213 (7):1143-52.
Effect of antihypertensive treatment on stroke recurrence. Hypertension-Stroke Cooperative Study Group. JAMA 1974; 229 (4):409-18.
Amery A, Birkenhager W, Brixko P et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet 1985; 1 (8442):1349-54.
Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. Br Med J (Clin Res Ed) 1986; 293 (6555):1145-51.
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24):3255-64.
Dahlof B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991; 338 (8778):1281-5.
Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992; 304 (6824):405-12.
Staessen JA, Fagard R, Thijs L et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997; 350 (9080):757-64.
This is an example of a treatment algorithm that incorporates the epidemiology and clinical information about the risk of elevated BP and benefits of risk modification. These guidelines were first published in 1976 and the current update in 2003.
Note the therapeutic goal in yellows; compare to the evidence above.
What expectations do you have about these guidelines from a public health perspective?
My public health perspective might be:
Individuals at high risk should be aware of their risk status
Interventions to modify risk associated with elevated BP, consistent with existing clinical evidence for therapeutic efficacy, should have been implemented in these individuals
Treated individuals should have attained recommended BP goals.
These expectations are consistent with the Healthy People 2020 goals from CDC
