European Heart Journal (1992) 13 {Supplement G), 34-42
Potency of vascular risk factors as the basis for antihypertensive therapy W. B. KANNEL
Framingham Study, Framingham MA, U.S.A. KEY WORDS: Hypertension, vascular risk factors, prognosis.
Introduction . . . . ., r Hypertension .s now recognized as a major risk factor for cardiovascular disease and .s now intensively sought out and treated'". Unfortunately, ,t ,s too often dealt with as an iso ated ent.ty rather than as an ingredient of a card.ovascular risk profile^. Failure to take into account the often associated risk factors which tend to cluster with hypertension and that markedly influence> the nsk of hypertension make it necessary to treat hundreds to benent one. High risk hypertension is concentrated in those with one or more other risk factors and, when this is taken into account, those likely to benefit can be more efficiently Supported by the Nalional Heart, Lung and Blood Institute, Grant NosNIH-
NOTHV-92922 and NIH-NOI-HV-52971; the Charles A. Dana Foundation, Merck sharpe and Dohme, Pfizer and ICI. : W. B. Kannel, Framingham Study, 5 Thurber Street, , MA 01701, U.S.A. 0I95-668X 92 OG0034+09S08.00,0
targeted for treatment and the proper treatment more rationally selected. Thjs
e x a m i n e s t h e i n f l u e n c e o f o t h e r risk f a c t o r s
f o r risk f a c . ideration of t o r s t() c ] u s t e r w i t h h y p e r t e n s i o n a n d t h e cons o t h e r Hsk factors as g basjs for a n t i h y p e r t e n s i v e therapy. „ -& b a s e d o n d a t a f r o m t h e F r a m i h a m S t u d y w h e r e ^hav£ ^ f o , l o w e d b i e n n i a l l f o r development of ^T^oyascxAar ^ ^ of hypertension and other risk f a c t o r s f o f m Q r e t h a n f o u r decades (3]
jn { h e h a z a r d o f h
tension> the t e n d e
Hazards of hypertension .
...
/• .
•
.
r u
_.
•
»L. • „•
Investigation of the impact of hypertension on the incidence of cardiovascular disease over three decades of surveillance of the Framingham Study Cohort indicates a powerful impact on all the major cardiovascular disease © 1992 The European Society of Cardiology
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 26, 2016
Hypertension is a powerful predisposing risk factor for cariovascular disease at all ages and in both sexes. Epidemiological assessment indicates the largest risk ratios for stroke and congestive heart failure (CHF), but coronary heart disease (CHD) is the most common and most lethal sequela of hypertension. Examination of the risk of cardiovascular sequelae in the hypertensive population indicates that this is not uniform and varies over a 10-fold range, depending on the associated risk factors. Systolic pressure merits greater consideration than the diastole pressure because isolated systolic hypertension is a powerful cardiovascular risk at all ages. Furthermore, recent trials have indicated the benefit of therapy for systolicbased hypertension in the elderly, even using a diuretic, for coronary disease as well as stroke. Persons with hypertension have a high prevalence of associated cardiovascular risk factors, including elevated cholesterol, reduced HDL-C, diabetes, left ventricular hypertrophy (LVH), and obesity. About 9% under the age of 65 years have an associated overt cardiovascular disease; above age 65 about 30% are so afflicted. Each of these risk factors can double the risk associated with hypertension. Because they are so common, a large fraction of the disease sequelae of hypertension is attributable to these associated risk factors. The high risk of coronary disease in hypertensive patients is concentrated in those with a high total/HDL-cholesterol ratio, impaired glucose tolerance, high fibrinogen, ECG abnormalities, and cigarette smokers. Stroke risk in hypertensive persons is concentrated in those with cardiovascular disease, diabetes, atrialfibrillation, L VH and cigarette smoking. Asfor CHD and cardiovascular disease in general, stroke risk varies over a 10-fold range, depending on the associated clustering of risk factors. Consideration of these cardiovascular risk factors is required to evaluate properly the needfor treatment, to select the best treatment and to set goals and determine the efficacy of treatment. Optimal therapy ofhypertension should improve the composite risk profile as well as blood pressure. Long-standing hypertension is commonly associated with angina, a myocardial infarction, cardiac failure, renal insufficiency, peripheral artery disease, retinopathy, stroke and left ventricular hypertrophy. Choice of therapy for hypertension accompanied by these conditions must be selected so as to benefit the associated conditions as well as the hypertension. Silent or unrecognized myocardial infarctions must be sought out since almost half of all Mis in hypertensive women and 35% of Mis in hypertensive men are clinically silent. ECG and anatomical evidence ofL VHeach independently triple the risk of hypertension and must be considered ominous harbingers of cardiovascular catastrophes. Thus, therapy for hypertension must take into account associated risk factors, concomitant disease, age, race and side effect profile. Therapy must also give more attention to step-down of drugs, hygienic measures such as weight control, salt and alcohol restriction, lessfat in the diet and potassium and magnesium supplementation. Hypertension must be dealt with as an ingredient of a cardiovascular risk profile requiring multivariate risk reduction.
Risk factors and antihypertensive therapy 35
50 45
Cardiac failure
Peripheral artery disease
Stroke
Coronary disease
T3 CD
!§=o a>
a?
23
21
If » m
14
12-4
c *~ c
10
9-5
10
6-2 3-3|
2-4|
1
0 Risk ratio. Excess risk-
•S-O
y
2-6***
2-0***
2-2***
3-8***
23
12
9
4
Men
Women
Men
Women
7-3
I
3-5
2-o
20*** 5 Men
3-7 5 Women
4-0*** 10 Men
6-3
2|
1
3-0*** 4 Women
Figure I Risk of cardiovascular events by hypertensive status in the Framingham Study in subjects 35-64 years of age, with a 36 year follow-up. • = normal; • = hypertension.
Age (years)
35-64 65-94
Risk ratio
Age-adjusted rate per 1000
Excess
risk
Men
Women
Men
Women
Men
Women
65 125
35 81
2-2*'* 1-8***
2-5*** 1-8*"
36 56
21 35
Hypertension = > 160/90 mmHg; Cardiovascular diseases = coronary heart disease, stroke, congestive heart failure, intermittent claudication. ***/ > =240 HDL < 35 Diabetes LVH (deferred) Smokes cigarettes Obese (mrw> = 130) CV disease Angina MI CHF Stroke IC CVD
Women
Normal 523
Borderline 337
Definite 237
Normal 656
Borderline 515
Definite 438
20-7% 26-8% 140% 2-0% 20-8% 19-5%
24-7% 21-3% 14-6% 2-7% 201% 21-5%
26-2% 14-3% 20-1 % 10-1% 211% 22-1%
43-9% 9-3% 10-2% 2-9% 16 3% 22-7%
50-3% 7-6% 12-2% 2-4% 14-9% 29-9%
51-8% 7-5% 15-2% 6-2% 12 2% 34-4%
15-3% 13-0% 3 4% 6-5% 80% 32-2%
15-2% 11-8% 1-4% 6-5% 6 9% 29-2%
12-2% 11-9% 3-0% 9-5% 90% 31-4%
10-5% 4-8% 3-4% 4-6% 2-8% 19-6%
11-9% 4-8% 3-0% 40% 3-8% 22-2%
160% 4-6% 4-9% 4-9% 6-2% 26-9%
The sample consists of offspring cycles 1 and 2 combined with the HDL measurements ofthe cohort at exams 10-12 and exam 15. All prevalence rates are age-adjusted. HDL = high density lipoprotein; LVH = left ventricular hypertrophy; MI =myocardial infarction; CHF = congestive heart failure; IC = intermittent claudication; CVD = cardiovascular disease.
of those without the risk factor. For men 35-64 years of age, hypertension ranks above serum cholesterol (240 mg . dl~') and smoking in absolute and excess risk, but below diabetes and ECG-LVH. For relative risk it ranks equal with diabetes (Table 3). For women, the impact of hypertension is well below that of diabetes for absolute, relative and excess risk, but well above that for serum cholesterol and smoking (Table 4). Above age 65 years for men the pattern of risk is similar to that for men under age 65, except that the absolute and excess risk is higher for all risk factors, including hypertension. The risk ratios for all risk factors, including hypertension, tend to decline with age, but this is offset by a higher absolute and excess risk. This makes treatment of hypertension in the elderly at least as cost effective as in the young (Table 1).
A more objective comparison of the strength of risk factors can be achieved by examining the risk of cardiovascular disease per standard deviation increment in each risk factor. This tends to place the risk factors on an equal footing for the different units of measurement. Examined in this fashion, blood pressure once again has the greatest impact on risk of a cardiovascular event, exceeding that of cholesterol, glucose and cigarette smoking in particular (Table 5). Each standard deviation increment in systolic blood pressure is associated with a 50% increase in incidence of cardiovascular events. Systolic vs diastolic pressure
Epidemiological data provide no support for the preference of diastolic over systolic blood pressure as an
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 26, 2016
CV risk factors Cholesterol > =240 HDL = 130) CV disease Angina MI CHF Stroke IC CVD
Women
Risk factors and antihypertensive therapy 37
Table3
Cardiovascular disease. Thirty-six yearfollow-up. Population at risk, free of event Males (age range 35-64 years)
Risk factor
Age-adjusted rate/1000 with r.f.
Age-adjusted rate/1000 without r.f.
Risk ratio
Excess risk
P value
SCL HBP Diabetes ECG-LVH Smoking
45 1 64-6 76-4 1640 45 4
26 1 290 34-5 34-6 26-3
1-73 2-23 2-21 4-74 1 73
190 35-6 41-9 129-4 191
Potency of vascular risk factors as the basis for antihypertensive therapy W. B. KANNEL
Framingham Study, Framingham MA, U.S.A. KEY WORDS: Hypertension, vascular risk factors, prognosis.
Introduction . . . . ., r Hypertension .s now recognized as a major risk factor for cardiovascular disease and .s now intensively sought out and treated'". Unfortunately, ,t ,s too often dealt with as an iso ated ent.ty rather than as an ingredient of a card.ovascular risk profile^. Failure to take into account the often associated risk factors which tend to cluster with hypertension and that markedly influence> the nsk of hypertension make it necessary to treat hundreds to benent one. High risk hypertension is concentrated in those with one or more other risk factors and, when this is taken into account, those likely to benefit can be more efficiently Supported by the Nalional Heart, Lung and Blood Institute, Grant NosNIH-
NOTHV-92922 and NIH-NOI-HV-52971; the Charles A. Dana Foundation, Merck sharpe and Dohme, Pfizer and ICI. : W. B. Kannel, Framingham Study, 5 Thurber Street, , MA 01701, U.S.A. 0I95-668X 92 OG0034+09S08.00,0
targeted for treatment and the proper treatment more rationally selected. Thjs
e x a m i n e s t h e i n f l u e n c e o f o t h e r risk f a c t o r s
f o r risk f a c . ideration of t o r s t() c ] u s t e r w i t h h y p e r t e n s i o n a n d t h e cons o t h e r Hsk factors as g basjs for a n t i h y p e r t e n s i v e therapy. „ -& b a s e d o n d a t a f r o m t h e F r a m i h a m S t u d y w h e r e ^hav£ ^ f o , l o w e d b i e n n i a l l f o r development of ^T^oyascxAar ^ ^ of hypertension and other risk f a c t o r s f o f m Q r e t h a n f o u r decades (3]
jn { h e h a z a r d o f h
tension> the t e n d e
Hazards of hypertension .
...
/• .
•
.
r u
_.
•
»L. • „•
Investigation of the impact of hypertension on the incidence of cardiovascular disease over three decades of surveillance of the Framingham Study Cohort indicates a powerful impact on all the major cardiovascular disease © 1992 The European Society of Cardiology
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 26, 2016
Hypertension is a powerful predisposing risk factor for cariovascular disease at all ages and in both sexes. Epidemiological assessment indicates the largest risk ratios for stroke and congestive heart failure (CHF), but coronary heart disease (CHD) is the most common and most lethal sequela of hypertension. Examination of the risk of cardiovascular sequelae in the hypertensive population indicates that this is not uniform and varies over a 10-fold range, depending on the associated risk factors. Systolic pressure merits greater consideration than the diastole pressure because isolated systolic hypertension is a powerful cardiovascular risk at all ages. Furthermore, recent trials have indicated the benefit of therapy for systolicbased hypertension in the elderly, even using a diuretic, for coronary disease as well as stroke. Persons with hypertension have a high prevalence of associated cardiovascular risk factors, including elevated cholesterol, reduced HDL-C, diabetes, left ventricular hypertrophy (LVH), and obesity. About 9% under the age of 65 years have an associated overt cardiovascular disease; above age 65 about 30% are so afflicted. Each of these risk factors can double the risk associated with hypertension. Because they are so common, a large fraction of the disease sequelae of hypertension is attributable to these associated risk factors. The high risk of coronary disease in hypertensive patients is concentrated in those with a high total/HDL-cholesterol ratio, impaired glucose tolerance, high fibrinogen, ECG abnormalities, and cigarette smokers. Stroke risk in hypertensive persons is concentrated in those with cardiovascular disease, diabetes, atrialfibrillation, L VH and cigarette smoking. Asfor CHD and cardiovascular disease in general, stroke risk varies over a 10-fold range, depending on the associated clustering of risk factors. Consideration of these cardiovascular risk factors is required to evaluate properly the needfor treatment, to select the best treatment and to set goals and determine the efficacy of treatment. Optimal therapy ofhypertension should improve the composite risk profile as well as blood pressure. Long-standing hypertension is commonly associated with angina, a myocardial infarction, cardiac failure, renal insufficiency, peripheral artery disease, retinopathy, stroke and left ventricular hypertrophy. Choice of therapy for hypertension accompanied by these conditions must be selected so as to benefit the associated conditions as well as the hypertension. Silent or unrecognized myocardial infarctions must be sought out since almost half of all Mis in hypertensive women and 35% of Mis in hypertensive men are clinically silent. ECG and anatomical evidence ofL VHeach independently triple the risk of hypertension and must be considered ominous harbingers of cardiovascular catastrophes. Thus, therapy for hypertension must take into account associated risk factors, concomitant disease, age, race and side effect profile. Therapy must also give more attention to step-down of drugs, hygienic measures such as weight control, salt and alcohol restriction, lessfat in the diet and potassium and magnesium supplementation. Hypertension must be dealt with as an ingredient of a cardiovascular risk profile requiring multivariate risk reduction.
Risk factors and antihypertensive therapy 35
50 45
Cardiac failure
Peripheral artery disease
Stroke
Coronary disease
T3 CD
!§=o a>
a?
23
21
If » m
14
12-4
c *~ c
10
9-5
10
6-2 3-3|
2-4|
1
0 Risk ratio. Excess risk-
•S-O
y
2-6***
2-0***
2-2***
3-8***
23
12
9
4
Men
Women
Men
Women
7-3
I
3-5
2-o
20*** 5 Men
3-7 5 Women
4-0*** 10 Men
6-3
2|
1
3-0*** 4 Women
Figure I Risk of cardiovascular events by hypertensive status in the Framingham Study in subjects 35-64 years of age, with a 36 year follow-up. • = normal; • = hypertension.
Age (years)
35-64 65-94
Risk ratio
Age-adjusted rate per 1000
Excess
risk
Men
Women
Men
Women
Men
Women
65 125
35 81
2-2*'* 1-8***
2-5*** 1-8*"
36 56
21 35
Hypertension = > 160/90 mmHg; Cardiovascular diseases = coronary heart disease, stroke, congestive heart failure, intermittent claudication. ***/ > =240 HDL < 35 Diabetes LVH (deferred) Smokes cigarettes Obese (mrw> = 130) CV disease Angina MI CHF Stroke IC CVD
Women
Normal 523
Borderline 337
Definite 237
Normal 656
Borderline 515
Definite 438
20-7% 26-8% 140% 2-0% 20-8% 19-5%
24-7% 21-3% 14-6% 2-7% 201% 21-5%
26-2% 14-3% 20-1 % 10-1% 211% 22-1%
43-9% 9-3% 10-2% 2-9% 16 3% 22-7%
50-3% 7-6% 12-2% 2-4% 14-9% 29-9%
51-8% 7-5% 15-2% 6-2% 12 2% 34-4%
15-3% 13-0% 3 4% 6-5% 80% 32-2%
15-2% 11-8% 1-4% 6-5% 6 9% 29-2%
12-2% 11-9% 3-0% 9-5% 90% 31-4%
10-5% 4-8% 3-4% 4-6% 2-8% 19-6%
11-9% 4-8% 3-0% 40% 3-8% 22-2%
160% 4-6% 4-9% 4-9% 6-2% 26-9%
The sample consists of offspring cycles 1 and 2 combined with the HDL measurements ofthe cohort at exams 10-12 and exam 15. All prevalence rates are age-adjusted. HDL = high density lipoprotein; LVH = left ventricular hypertrophy; MI =myocardial infarction; CHF = congestive heart failure; IC = intermittent claudication; CVD = cardiovascular disease.
of those without the risk factor. For men 35-64 years of age, hypertension ranks above serum cholesterol (240 mg . dl~') and smoking in absolute and excess risk, but below diabetes and ECG-LVH. For relative risk it ranks equal with diabetes (Table 3). For women, the impact of hypertension is well below that of diabetes for absolute, relative and excess risk, but well above that for serum cholesterol and smoking (Table 4). Above age 65 years for men the pattern of risk is similar to that for men under age 65, except that the absolute and excess risk is higher for all risk factors, including hypertension. The risk ratios for all risk factors, including hypertension, tend to decline with age, but this is offset by a higher absolute and excess risk. This makes treatment of hypertension in the elderly at least as cost effective as in the young (Table 1).
A more objective comparison of the strength of risk factors can be achieved by examining the risk of cardiovascular disease per standard deviation increment in each risk factor. This tends to place the risk factors on an equal footing for the different units of measurement. Examined in this fashion, blood pressure once again has the greatest impact on risk of a cardiovascular event, exceeding that of cholesterol, glucose and cigarette smoking in particular (Table 5). Each standard deviation increment in systolic blood pressure is associated with a 50% increase in incidence of cardiovascular events. Systolic vs diastolic pressure
Epidemiological data provide no support for the preference of diastolic over systolic blood pressure as an
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 26, 2016
CV risk factors Cholesterol > =240 HDL = 130) CV disease Angina MI CHF Stroke IC CVD
Women
Risk factors and antihypertensive therapy 37
Table3
Cardiovascular disease. Thirty-six yearfollow-up. Population at risk, free of event Males (age range 35-64 years)
Risk factor
Age-adjusted rate/1000 with r.f.
Age-adjusted rate/1000 without r.f.
Risk ratio
Excess risk
P value
SCL HBP Diabetes ECG-LVH Smoking
45 1 64-6 76-4 1640 45 4
26 1 290 34-5 34-6 26-3
1-73 2-23 2-21 4-74 1 73
190 35-6 41-9 129-4 191
