Target-organ
damage in hypertension: who is at risk?
Charles G.C. Spencer, Gregory Y.H. Lip
University Department of Medicine, City Hospital, Birmingham, UK
Correspondence: Dr GYH Lip University Department of Medicine, City Hospital,
Birmingham B18 7QH, UK. Tel: +44-121 507 5080, fax: +44 121 554 4083, e-mail: g.y.h.lip@bham.ac.uk
Introduction
One of the paradoxes of hypertension is that, overall, many patients have to
be treated in order to prevent one cardiovascular adverse event. For example,
in the Medical Research Council trial of the treatment of mild hypertension,
2000 patients with a diastolic blood pressure of 95–99 mmHg had to be treated
in order to prevent one stroke.[1] However, the risks associated
with hypertension are not uniform, and indeed many hypertensives continue
to suffer heart attacks and strokes despite treatment to reduce their blood
pressure.[2] There is therefore increasing emphasis on the
estimation of absolute cardiovascular risk when assessing individual patients
with hypertension, in order to target patients at highest risk for antihypertensive
therapy.[3] The recent joint recommendations published by
the British Cardiac Society, British Hyperlipidaemia Association, British
Hypertension Society, and British Diabetic Association[4] emphasize
risk stratification based upon a combination of age, sex, blood pressure
levels, the presence or absence of diabetes mellitus, and serum cholesterol.
In particular, hypertensive patients with evidence of target-organ damage
are well-recognized to be at high risk of cardiovascular and cerebrovascular
events, and should be targeted for aggressive management.
Hypertension causes target-organ damage by the direct physical effect of increased
blood pressure, as well as the promotion of atherosclerosis and thrombogenesis,
leading to a prothrombotic or hypercoagulable state.[5] These
‘target-organ’ effects occur throughout the body but are particularly manifest
in the heart, brain, kidney, peripheral arteries and the eye.
The heart
Hypertension damages the heart by its direct effect on the heart muscle itself
and by the promotion of coronary artery disease. The heart responds to the
increased afterload imposed by hypertension by developing left ventricular
hypertrophy (LVH). According to Laplace’s law, left ventricular wall stress
is proportional to intracavity pressure and left ventricular radius, and is
inversely proportional to wall thickness. By developing LVH, wall stress is
maintained at the same level at the expense of increased wall thickness. This
adaptation, however, significantly increases myocardial oxygen demand at the
same time as decreasing coronary flow reserve.[6]
Left ventricular hypertrophy
LVH, whether measured by electrocardiography (ECG) or by echocardiography,
is a marker of poor prognosis in hypertensive patients, increasing the risk
of sudden death, ventricular arrhythmias, congestive cardiac failure and stroke.
For example, the age-adjusted all-cause mortality for hypertensives with LVH
was 43.2 per 1000 patient-years, compared with 27.6 for those with normal ECGs;
furthermore, those with both LVH and ST-T changes (‘strain’ pattern) had their
mortality doubled, with an age-adjusted all-cause mortality of 56.9 per 1000
patient years.[7] Although LVH is causally related to hypertension,[8] the
correlation between level of blood pressure and LVH is poor, and other factors
such as adrenergic stimulation, the renin-angiotensin system and various growth
factors appear to be involved.[6]
Why is LVH such an adverse feature in hypertension? The presence of LVH may
result in the following: (1) mismatch of blood supply and non-vascular tissue,
resulting in a relatively ‘starved’ subendocardial region; (2) increased basal
myocardial oxygen demand due to increased mass and wall stress; (3) heightened
likelihood of ventricular arrhythmias, perhaps related to fibrous tissue; and
(4) markedly reduced coronary flow reserve, with abnormalities in the ability
to dilate coronary arteries, resulting in increased cardiac ischaemia.[9]
The increased mortality with LVH can be graded according to the increasing
voltage on the ECG. In an analysis from the Framingham study which divided
those with LVH into four quartiles according to voltage, the age-adjusted odds
ratio for cardiovascular disease between the highest and lowest quartiles was
3.08 for men and 3.29 for women.[8] In this longitudinal study,
subjects with a serial decline in voltage were at reduced risk, whilst there
was an increase in risk for those in whom the voltage increased over time,
indicating that LVH is a risk factor which is amenable to modification.8 Whilst
the ECG is commonly used to assess the presence of LVH, for example by Sokolow-Lyon
criteria (the sum of the S-wave in lead V1 + R-wave in leads V5 or V6 = 35
mm), it is relatively insensitive at detecting LVH. Indeed, many patients with
normal ECGs will have LVH when examined by echocardiography, which is probably
the gold standard for assessing LVH.[10] These patients are
at similarly high risk, with an all-cause mortality several times that of those
with normal echocardiograms.[11]
Hypertensive LVH is responsible for increased cardiovascular morbidity and
mortality by a number of mechanisms. These patients have an increased risk
of cardiovascular events, heart failure and cardiac dysfunction, atherosclerotic
vascular disease, arrhythmias and sudden death. For a given level of blood
pressure, and if LVH is present, the prognosis is three or four times worse,
especially for cardiac failure and stroke. The presence of LVH is also a risk
factor for the development of cardiac arrhythmias, the commonest of these being
atrial fibrillation and ventricular arrhythmias. The presence of atrial fibrillation
is important, as this arrhythmia is associated with a fivefold increase in
mortality and may often require long-term antiarrhythmic and antithrombotic
therapy. In addition, ventricular arrhythmias have important implications for
the risk of sudden death in these patients.[12] The mechanisms
for sudden death are complex, and may include malignant cardiac arrhythmias,
including increased ventricular ectopics and non-sustained ventricular tachycardia.[13,14] Indeed,
non-sustained ventricular tachycardia has been shown to occur in 28% of hypertensive
patients with ECG evidence of LVH compared with 8% of those with a normal ECG.
There is evidence of myocardial ischaemia in LVH even in the presence of normal
coronary arteries, and in the event of coronary artery occlusion there is an
increase in infarct size and infarct-related death.[15] However,
the risk of sudden death is independent of arterial pressure.[9] Electrophysiological
mechanisms for arrhythmogenesis in LVH include the following: re-entry mechanisms
related to myocardial fibrosis in LVH; myocardial ischaemic areas, perhaps
related to reduced coronary reserve (as coronary artery disease is often not
present); ventricular myocyte stretching and arterial wall tension in the hypertrophied
heart; and, finally, increased sympathetic nervous system activity.[9]
Coronary artery disease
Given that hypertension is a major cause of coronary artery disease,[16] it
is inevitable that many patients with angina and myocardial infarction will
have hypertension. These patients are at very high risk of further events,
as illustrated by the Multiple Risk Factor Intervention Trial, which found
a 15-year coronary heart disease mortality of 32% in middle-aged men with prior
myocardial infarction and systolic blood pressures above 160 mmHg.[17] Hypertensive
patients with specific ECG abnormalities suggestive of coronary artery disease,
such as Q-waves, are also at high risk.[18] Analysis of the
large treatment trials suggests that adequate treatment of hypertension reduces
heart attack risk by approximately 25%, although this analysis is based on
blood pressure reduction using thiazides and beta-blockers rather than the
newer antihypertensive drugs.
Heart failure
Convincing evidence from prospective epidemiological studies suggests that
heart failure may be caused by high blood pressure and be prevented by its
control. For example, the Framingham study suggested that high blood pressure
was the principal cause of heart failure.[19] Furthermore,
hypertension increases the risk of coronary heart disease and subsequent myocardial
infarction which can lead to damaged ventricles and heart failure. The relative
importance of hypertension alone and of hypertension-associated heart attacks
in causing heart failure is probably influenced by the availability of diagnostic
techniques and the criteria for diagnosing hypertension employed in different
studies. Finally, LVH is also a powerful predictor of cardiac failure.[19] The
development of atrial fibrillation, especially if hypertensive LVH and diastolic
dysfunction are present, can precipitate heart failure.
The brain
Despite its capacity for autoregulating its blood supply over a wide range
of blood pressures, the brain is highly vulnerable to the effects of hypertension.
Hypertension causes cerebrovascular disease by promoting aortic and carotid
atherosclerosis, by causing arteriosclerosis and/or thrombosis of small penetrating
cerebral end-arteries, by predisposing to heart disease (such as atrial fibrillation)
that may lead to stroke, and finally, by predisposing to intracranial haemorrhage.[20] Hypertension
is also well-recognized as an important cause of dementia.[21]
Patients with a history of stroke or transient ischaemic attack are at high
risk not only of further stroke but also of coronary artery disease, and this
risk is related directly to blood pressure.[22] The presence
of a carotid stenosis or increased carotid artery intima and media thickness
on ultrasonography are indicators of high cardiovascular risk, even in the
absence of previous stroke.[23,24]
Peripheral arterial disease
Considering the role of hypertension in the development of atherosclerosis,
it is not surprising that many patients with peripheral arterial disease
have hypertension. Like those with coronary artery disease, patients with
severe symptomatic peripheral artery disease are at very high risk of cardiovascular
death, with a 15-fold increase in cardiovascular mortality and coronary heart
disease.[25] Even those with asymptomatic peripheral arterial
disease diagnosed by the simple clinical measurement of ankle/arm systolic
blood pressure index, have a relative risk for cardiovascular mortality of
3.2.[26]
The kidney
There is controversy as to whether renal disease in hypertension truly represents
target-organ damage. Although renal dysfunction in the form of raised serum
creatinine is often found in hypertension, conclusive evidence that it is actually
caused by elevated blood pressure in patients with non-malignant essential
hypertension is lacking.[27] There is, however, a substantial
body of evidence that renal disease can cause hypertension. Certainly the number
of patients in the large hypertension trials who developed new renal disease
during follow-up is very small compared with those developing myocardial infarctions
or strokes.[27]
Nevertheless, hypertensive patients with evidence of renal dysfunction are
at high risk. Those with a raised serum creatinine[28] and
overt proteinuria[29] have a particularly poor prognosis
in both cardiovascular and renal terms. In patients with malignant-phase hypertension,
the presence of renal dysfunction is an independent prognostic risk factor.[30] Much
interest has also been aroused by the possibility that microalbuminuria might
be a marker of early renal damage and cardiovascular risk in hypertension.
Indeed, a number of studies have shown a relationship between microalbuminuria
and cardiovascular risk in the general population,[31] as
well as markers of target-organ damage[32] and endothelial
dysfunction[33] in hypertensives. Nevertheless, convincing
evidence of its usefulness as an independent marker of risk in treated non-diabetic
hypertensives awaits further trial evidence.
The eye
Funduscopy provides a unique opportunity to directly visualize the blood vessels
in hypertensives in order to assess target-organ involvement in the eye. Nearly
all forms of retinal damage are common in people with high blood pressure and
these include retinal haemorrhage and both venous and arteriolar central retinal
vascular occlusion, all of which may lead to blindness. The most widely used
classification of fundus changes in hypertension is that of Keith, Wagener
and Barker[34] (Table 1).
 Table
1. The Keith, Wagener and Barker classification of essential
hypertension and prognosis according to hypertensive retinopathy
categories.[34]
The strength of this classification is the correlation
between clinical findings and prognosis, although there is only
a significant difference in prognosis between the top two grades
indicative of malignant hypertension and the bottom two grades
(non-malignant). For everyday clinical practice this is the only
useful prognostic information to be obtained from funduscopy,
thus Dodson et al.[35] have proposed a simpler
classification of hypertensive retinopathy into ‘malignant’ (incorporating
Keith, Wagener and Barker grades III and IV) and ‘non-malignant’
grades (grades I and II).
Conclusion
We have seen that the presence of target-organ damage makes a dramatic difference
to prognosis in hypertension. All hypertensives should be assessed for target-organ
damage by history, physical examination and other appropriate investigations
where necessary. These patients deserve concerted action to reduce not only
their blood pressure but also their overall level of cardiovascular risk.
REFERENCES
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Comment in:
MRC trial of treatment of mild hypertension: principal
results. Medical Research Council Working Party.
The main aim of the trial was to determine whether drug treatment of mild
hypertension (phase V diastolic pressure 90-109 mm Hg) reduced the rates
of stroke, of death due to hypertension, and of coronary events in men and
women aged 35-64 years. Subsidiary aims were: to compare the course of blood
pressure in two groups, one taking bendrofluazide and one taking propranolol,
and to compare the incidence of suspected adverse reactions to these two
drugs. The study was single blind and based almost entirely in general practices;
17 354 patients were recruited, and 85 572 patient years of observation have
accrued. Patients were randomly allocated at entry to take bendrofluazide
or propranolol or placebo tablets. The primary results were as follows. The
stroke rate was reduced on active treatment: 60 strokes occurred in the treated
group and 109 in the placebo group, giving rates of 1.4 and 2.6 per 1000
patient years of observation respectively (p less than 0.01 on sequential
analysis). Treatment made no difference, however, to the overall rates of
coronary events: 222 events occurred on active treatment and 234 in the placebo
group (5.2 and 5.5 per 1000 patient years respectively). The incidence of
all cardiovascular events was reduced on active treatment: 286 events occurred
in the treated group and 352 in the placebo group, giving rates of 6.7 and
8.2 per 1000 patient years respectively (p less than 0.05 on sequential analysis).
For mortality from all causes treatment made no difference to the rates.
There were 248 deaths in the treated group and 253 in the placebo group (rates
5.8 and 5.9 per 1000 patient years respectively). Several post hoc analyses
of subgroup results were also performed but they require very cautious interpretation.
The all cause mortality was reduced in men on active treatment (157 deaths
versus 181 in the placebo group; 7.1 and 8.2 per 1000 patient years respectively)
but increased in women on active treatment (91 deaths versus 72; 4.4 and
3.5 per 1000 patient years respectively). The difference between the sexes
in their response to treatment was significant (p = 0.05). Comparison of
the two active drugs showed that the reduction in stroke rate on bendrofluazide
was greater than that on propranolol (p = 0.002). The stroke rate was reduced
in both smokers and non-smokers taking bendrofluazide but only in non-smokers
taking propranolol. This difference between the responses to the two drugs
was significant (p = 0.03).(ABSTRACT TRUNCATED AT 400 WORDS)
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- Clinical Trial
- Randomized Controlled Trial
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Mortality in patients of the Glasgow Blood
Pressure Clinic.
Isles CG, Walker LM, Beevers GD, Brown I, Cameron HL,
Clarke J, Hawthorne V, Hole D, Lever AF, Robertson JW,
et al.
The mortality of 3783 non-malignant hypertensive patients attending the Glasgow
Blood Pressure Clinic between 1968 and 1983 and followed for an average of
6.5 years was compared with that in three control groups: the general population
of Strathclyde a group of 15 422 subjects aged 45-64 years and screened in
Renfrew and Paisley between 1972 and 1976, and a group of hypertensives seen
in a blood pressure clinic based on general practice in Renfrew. Average
blood pressure for men at entry to the Glasgow Clinic was 181/111 mmHg falling
to 158/96 mmHg during treatment. Corresponding values for women were 185/109
mmHg and 161/96 mmHg. Seven hundred and fifty clinic patients (451 males)
died during follow-up, the commonest causes of death in both sexes being
myocardial infarction and stroke. All-cause age-adjusted mortality (deaths
per 1000 patient-years) was 41.4 for men and 22.1 for women. At all ages
in both sexes and for all levels of initial blood pressure mortality was
less in patients whose blood pressure was reduced most. Without a randomized
control group it is not certain that lower mortality in those with well controlled
blood pressure was due to treatment, although this is the most likely explanation.
Cigarette smoking, a history of myocardial infarction, angina or stroke,
retinal arterio-venous nipping, raised blood urea, an abnormal electrocardiogram
(ECG) and secondary hypertension were associated with increased risk, but
heavy alcohol intake, obesity, haematocrit greater than 45%, hypokalaemia
and social class were not. Life table analysis showed that, despite some
reduction of mortality by treatment, the relative risk to men and women in
the clinic remained two- to five-times that of the general population. The
benefits of treatment were not such as to restore normal expectation of life
even when blood pressure was well controlled. Excess mortality in the clinic
could not be explained by difference of smoking habit or social class. This
suggests that there is in the hypertensive patients of the Glasgow Clinic
an element of irreducible risk, that treatment may be beneficial in some
respects but harmful in others, or that patients at particularly high risk
are selectively referred to the clinic.
PMID: 3711657 [PubMed - indexed for MEDLINE]
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1999 World Health Organization-International Society
of Hypertension Guidelines for the Management of Hypertension. Guidelines
Subcommittee.
Publication Types:
- Guideline
- Practice Guideline
PMID: 10067786 [PubMed - indexed for MEDLINE]
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Joint British recommendations on prevention
of coronary heart disease in clinical practice. British Cardiac
Society, British Hyperlipidaemia Association, British Hypertension
Society, endorsed by the British Diabetic Association.
Publication Types:
- Guideline
- Practice Guideline
PMID: 10193438 [PubMed - indexed for MEDLINE]
5. Lip GYH, Li-Saw-He FL. Does hypertension confer a hypercoagulable
state? J Hypertens 1998; 16: 913–916.
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Erratum in:
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Comment in:
The heart in hypertension.
Frohlich ED, Apstein C, Chobanian AV, Devereux RB, Dustan HP, Dzau V,
Fauad-Tarazi F, Horan MJ, Marcus M, Massie B, et al.
Alton Ochsner Medical Foundation, New Orleans, LA 70121.
Publication Types:
PMID: 1518549 [PubMed - indexed for MEDLINE]
-
Left ventricular hypertrophy and mortality
in hypertension: an analysis of data from the Glasgow Blood
Pressure Clinic.
Dunn FG, McLenachan J, Isles CG, Brown I, Dargie HJ,
Lever AF, Lorimer AR, Murray GD, Pringle SD, Robertson
JW.
Cardiology Department, Stobhill General Hospital, Glasgow, UK.
Three thousand seven hundred and eighty-three patients with non-malignant
hypertension attending the Glasgow Blood Pressure Clinic between 1968 and
1983 were followed prospectively for an average of 6.5 years. Left ventricular
hypertrophy (LVH) was present at the outset in 34.5% of the men, and 12.8%
had ST-T changes. The corresponding figures for women were 21.5% and 8.8%.
The prevalence of LVH increased with the severity of hypertension and was
higher for a given blood pressure level in men than in women. All-cause age-adjusted
mortality, expressed as deaths per 1000 patient-years, was 27.6 for men with
normal electrocardiographs, 43.2 for men with LVH only (P less than 0.001)
and 56.9 for men with LVH and ST-T changes (P less than 0.001). Similar trends
were seen in women. The excess risk associated with LVH, with or without
ST-T changes, could not be explained by age, increased blood pressure at
referral to the clinic, or smoking habit, when these factors were considered
either separately or in combination (regression analysis). Thus, our study
demonstrates that LVH, with or without ST-T changes is an independent risk
factor for mortality in hypertensive patients.
PMID: 2170517 [PubMed - indexed for MEDLINE]
-
Prognostic implications of baseline electrocardiographic
features and their serial changes in subjects with left ventricular
hypertrophy.
Levy D, Salomon M, D'Agostino RB, Belanger AJ, Kannel
WB.
Framingham Heart Study, MA 01701.
BACKGROUND: During the past half-century, the ECG has been used extensively
for the diagnosis of left ventricular hypertrophy. Persons with ECG evidence
of left ventricular hypertrophy are at increased risk for the development
of cardiovascular disease. METHODS AND RESULTS: Subjects from the Framingham
Heart Study with ECG evidence of left ventricular hypertrophy were eligible
for this investigation if they were free of cardiovascular disease and did
not have complete bundle-branch block or Wolff-Parkinson-White syndrome.
Logistic regression analyses of pooled biennial examinations were used to
determine risk for cardiovascular disease as a function of baseline voltage
(sum of R wave in aVL plus S wave in V3) and repolarization and as a function
of serial changes in these ECG features of hypertrophy. The eligible sample
consisted of 274 men (mean age, 60 years) and 250 women (mean age, 64 years)
who contributed 2660 person-examinations. During follow-up, there were 269
new cardiovascular events. Compared with subjects in the first quartile of
voltage at baseline, the age-adjusted odds ratio for cardiovascular disease
among subjects in the fourth quartile was 3.08 (95% confidence interval [CI],
1.87 to 5.07) in men and 3.29 (95% CI, 1.78 to 6.09) in women. Compared with
a normal repolarization pattern, the presence of severe repolarization abnormalities
was associated with an age-adjusted odds ratio of 5.84 (95% CI, 3.55 to 9.62)
in men and 2.47 (95% CI, 1.38 to 4.42) in women. Subjects with a serial decline
in voltage were at lower risk for cardiovascular disease than were those
with no serial change (men: odds ratio after adjusting for age and baseline
voltage, 0.46; 95% CI, 0.26 to 0.84; women: odds ratio, 0.56; 95% CI, 0.30
to 1.04). In contrast, those with a serial increase in voltage were at greater
risk for cardiovascular disease (men: odds ratio, 1.86; 95% CI, 1.14 to 3.03;
women: odds ratio, 1.61; 95% CI, 0.91 to 2.84). Compared with those with
no serial change, an improvement in repolarization was associated with a
marginally significant reduction in cardiovascular risk in men (odds ratio
after adjusting for age and baseline repolarization, 0.45; 95% CI, 0.20 to
1.01). Worsening of repolarization was associated with increased risk for
cardiovascular disease in both sexes (men: odds ratio, 1.89; 95% CI, 1.05
to 3.40; women: odds ratio, 2.02; 95% CI, 1.07 to 3.81). CONCLUSIONS: The
results of this investigation suggest that regression of ECG features of
left ventricular hypertrophy confers an improvement in risk for cardiovascular
disease, whereas serial worsening imposes increased risk. The benefits to
be derived from regression of left ventricular hypertrophy must be confirmed
in other clinical settings.
PMID: 7923663 [PubMed - indexed for MEDLINE]
-
Left ventricular hypertrophy, arterial
hypertension and sudden death.
Messerli FH.
Department of Internal Medicine, Ochsner Clinic, New Orleans, Louisiana 70121.
Left ventricular hypertrophy has been identified as a powerful risk factor
for sudden death and for general cardiovascular morbidity and mortality.
Left ventricular hypertrophy has been documented as giving rise to ventricular
ectopy, even in the absence of myocardial ischemia. Mechanisms of ectopic
impulse generation in left ventricular hypertrophy are multifactorial and
involve enlarged myocytes, focal areas of fibrosis, and subendocardial ischemia,
as well as medial hypertrophy of the coronary arteries impeding homogeneous
impulse propagation throughout the myocardium. Left ventricular hypertrophy
can be reduced by specific antihypertensive therapy although not all antihypertensive
agents are equally effective. A reduction of left ventricular hypertrophy
with calcium antagonists, and possibly also with beta-blockers, has been
shown to diminish ventricular arrhythmias. Whether or not such a reduction
of left ventricular hypertrophy and suppression of ventricular ectopy will
improve their unfavorable prognosis remains to be determined.
Publication Types:
PMID: 2151334 [PubMed - indexed for MEDLINE]
-
Echocardiographic assessment of cardiac
anatomy and function in hypertensive subjects.
Savage DD, Drayer JI, Henry WL, Mathews EC Jr, Ware
JH, Gardin JM, Cohen ER, Epstein SE, Laragh JH.
Cardiovascular complications are a major source of morbidity and mortality
in hypertensive patients. To assess the prevalence of anatomic and functional
abnormalities of the heart in such patients, we studied 234 asymptomatic
subjects with mild-to-moderate systemic hypertension by echocardiography.
After adjusting the echocardiographic values for age and body surface area,
we found abnormally increased ventricular septal and/or posterobasal free-wall
thickness in 61% of the hypertensive subjects. We found increased left atrial,
aortic root, and left ventricular internal dimension (at end-diastole) in
5-7%, and decreased mitral valve closing velocity (E-F slope) and left ventricular
ejection fraction were noted in six and 15% of the subjects, respectively.
Four percent of the patients had disproportionate septal thickening (i.e.,
ventricular septal-to-left ventricular free-wall thickness ratio greater
than or equal to 1.3). In contrast to the high prevalence of cardiac abnormalities
detected by echocardiography, less than 10% of the hypertensive subjects
had abnormal 12-lead ECGs or abnormal chest x-rays. These findings demonstrate
a high prevalence of cardiac abnormalities in a population of asymptomatic
hypertensive subjects. These abnormalities can be detected by echocardiography
before they are otherwise apparent.
PMID: 421302 [PubMed - indexed for MEDLINE]
Relation of left ventricular mass and
geometry to morbidity and mortality in uncomplicated essential
hypertension.
Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH.
New York Hospital-Cornell Medical Center, New York.
OBJECTIVE: To assess the prognostic significance of left ventricular mass
and geometry in initially healthy persons with essential hypertension. DESIGN:
An observational study of a prospectively identified cohort. SETTING: University
medical center. PATIENTS: Two hundred and eighty patients with essential
hypertension and no pre-existing cardiac disease were evaluated using echocardiography
between 1976 and 1981. Two hundred and fifty-three subjects or their family
members (90%) were contacted for a follow-up interview an average of 10.2
years after the initial echocardiogram was obtained; the survival status
of 27 patients lost to follow-up was ascertained using National Death Index
data. MEASUREMENTS AND MAIN RESULTS: Left ventricular mass exceeded 125 g/m2
in 69 of 253 patients (27%). Cardiovascular events occurred in a higher proportion
of patients with than without left ventricular hypertrophy (26% compared
with 12%; P = 0.006). Patients with increased ventricular mass were also
at higher risk for cardiovascular death (14% compared with 0.5%; P less than
0.001) and all-cause mortality (16% compared with 2%; P = 0.001). Electrocardiographic
left ventricular hypertrophy did not predict risk. Patients with normal left
ventricular geometry had the fewest adverse outcomes (no cardiac deaths;
morbid events in 11%), and those with concentric hypertrophy had the most
(death in 21%; morbid events in 31%). In a multivariate analysis, only age
and left ventricular mass--but not gender, blood pressure, or serum cholesterol
level--independently predicted all three outcome measures. CONCLUSIONS: Echocardiographically
determined left ventricular mass and geometry stratify risk in patients with
essential hypertension independently of and more strongly than blood pressure
or other potentially reversible risk factors and may help to stratify the
need for intensive treatment.
PMID: 1825164 [PubMed - indexed for MEDLINE]-
Precursors of sudden coronary death. Factors
related to the incidence of sudden death.
Kannel WB, Doyle JT, McNamara PM, Quickenton P, Gordon T.
Precursors of sudden death were sought in men--1838 civil servants in Albany,
New York, and 2282 residents of Framingham, Massachusetts--under continuous
surveillance for 16 years. In men 45-74 years old there were 234 deaths attributed
to coronary heart disease (CHD) of which 109 occurred within one hour of
onset of symptoms. More than half of all deaths due to CHD occurred outside
the hospital and about 80 per cent of these were sudden. Most were unheralded
by prior symptoms of CHD. Persons at high risk of death from CHD, including
sudden death, can be identified long before the terminal unexpected catastrophe.
The same precursive stigmata exist in persons subject ot coronary attacks
whether or not immediately fatal. The risk of sudden death in these two populations
was positively correlated with high blood pressure, the electrocardiographic
pattern of left ventricular enlargement, obesity, and heavy cigarette usage.
Sudden death is a common and possibly incidental expression of lethal coronary
heart disease. The potential candidate for sudden death cannot be confidently
distinguished from the individual who succumbs more slowly of myocardial
infarction. The inescapable conclusion is that the prevention of sudden death
requires the prevention of coronary attacks.
PMID: 123182 [PubMed - indexed for MEDLINE]-
Ventricular arrhythmias in patients with
hypertensive left ventricular hypertrophy.
McLenachan JM, Henderson E, Morris KI, Dargie HJ.
In patients with hypertension, a pattern of left ventricular hypertrophy
on the electrocardiogram is associated with a risk of sudden death in excess
of the risk attributable to hypertension alone. We therefore investigated
the frequency of complex ventricular arrhythmias by means of 48-hour ambulatory
electrocardiographic monitoring in 100 treated hypertensive patients, of
whom 50 had electrocardiographic evidence of left ventricular hypertrophy
and 50 did not, and in 50 normotensive controls. The groups were matched
for age, sex, and smoking habits, and the two hypertensive groups were matched
for blood-pressure levels before and after antihypertensive therapy. Nonsustained
ventricular tachycardia, defined as greater than or equal to 3 complexes
at a rate greater than or equal to 120 beats per minute, occurred in 14 (28
percent) of the 50 patients with an electrocardiographic pattern of left
ventricular hypertrophy, in 4 (8 percent) of the 50 patients without hypertrophy
(P less than 0.05), and in 1 (2 percent) of the control subjects. Eight of
the 50 patients (16 percent) with hypertrophy had episodes of nonsustained
ventricular tachycardia longer than 5 complexes, whereas no patients without
hypertrophy and no controls had such episodes. The group with nonsustained
ventricular tachycardia was characterized by a high left ventricular mass
on echocardiography and a high prevalence of ST-T abnormalities on electrocardiography.
Ventricular tachycardia was not closely related to blood-pressure levels,
nor was it associated with diuretic therapy or hypokalemia. The clinical
importance of these arrhythmias is uncertain. Nevertheless, our data suggest
that complex ventricular arrhythmias occur commonly in hypertensive patients
with left ventricular hypertrophy and may contribute to the higher incidence
of sudden death in these patients.
PMID: 2957590 [PubMed - indexed for MEDLINE]-
Pathophysiologic assessment of left ventricular
hypertrophy and strain in asymptomatic patients with essential
hypertension.
Pringle SD, Macfarlane PW, McKillop JH, Lorimer AR, Dunn
FG.
University Department of Medical Cardiology, Royal Infirmary, Glasgow, Scotland.
To investigate the significance of the electrocardiographic (ECG) pattern
of left ventricular hypertrophy and strain, two groups of asymptomatic patients
with essential hypertension were compared. The patients were similar in terms
of age, smoking habit, serum cholesterol and blood pressure levels, but differed
in the presence (Group I, n = 23) or absence (Group II, n = 23) of the ECG
pattern of left ventricular hypertrophy and strain. Group I patients had
significantly more episodes of exercise-induced ST segment depression (14
versus 4, p less than 0.05) and reversible thallium perfusion abnormalities
(11 of 23 versus 3 of 23, p less than 0.05) despite similar exercise capacity
and absence of chest pain. Nonsustained ventricular tachycardia was detected
on 24 h ambulatory ECG monitoring in two patients in Group I, but no patient
in Group II. Coronary arteriography performed in 20 Group I patients demonstrated
significant coronary artery disease in 8 patients. This study has shown that
there is a subgroup of hypertensive patients with ECG left ventricular hypertrophy
and strain who have covert coronary artery disease. This can be detected
by thallium perfusion scintigraphy, and may contribute to the increased risk
known to be associated with this ECG abnormality.
PMID: 2522959 [PubMed - indexed for MEDLINE]-
Left ventricular hypertrophy and myocardial
ischemia in systemic hypertension.
Dunn FG, Pringle SD.
Department of Medical Cardiology, Stobhill General Hospital, Glasgow, Scotland.
Considerable attention has properly been focused in recent years on electrocardiographic
abnormalities in patients with essential hypertension. It has been well established
that both voltage evidence of left ventricular (LV) hypertrophy and LV hypertrophy
and strain are ominous risk factors. A better understanding of the strain
pattern in patients with LV hypertrophy has arisen from experimental animal
studies showing how an increase in cardiac mass can lead to myocardial ischemia
and from clinical studies showing that the patient with LV hypertrophy and
strain is at risk from myocardial ischemia as a consequence of both associated
coronary artery disease and increased LV mass. All the clinical syndromes
associated with myocardial ischemia are increased in patients with LV hypertrophy
and therefore earlier recognition of both cardiac involvement and myocardial
ischemia is likely to improve survival in this particularly high-risk group
of patients.
PMID: 2961246 [PubMed - indexed for MEDLINE]-
Comment in:
Blood pressure, stroke, and coronary heart disease.
Part 1, Prolonged differences in blood pressure: prospective observational
studies corrected for the regression dilution bias.
MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton
J, Abbott R, Godwin J, Dyer A, Stamler J.
Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford,
UK.
The associations of diastolic blood pressure (DBP) with stroke and with
coronary heart disease (CHD) were investigated in nine major prospective
observational studies: total 420,000 individuals, 843 strokes, and 4856
CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate
positive, continuous, and apparently independent associations, with no
significant heterogeneity of effect among different studies. Within the
range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below
which lower levels of DBP were not associated with lower risks of stroke
and of CHD. Previous analyses have described the uncorrected associations
of DBP measured just at "baseline" with subsequent disease rates.
But, because of the diluting effects of random fluctuations in DBP, these
substantially underestimate the true associations of the usual DBP (ie,
an individual's long-term average DBP) with disease. After correction for
this "regression dilution" bias, prolonged differences in usual
DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least
34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD.
These associations are about 60% greater than in previous uncorrected analyses.
(This regression dilution bias is quite general, so analogous corrections
to the relations of cholesterol to CHD or of various other risk factors
to CHD or to other diseases would likewise increase their estimated strengths.)
The DBP results suggest that for the large majority of individuals, whether
conventionally "hypertensive" or "normotensive", a
lower blood pressure should eventually confer a lower risk of vascular
disease.
Publication Types:
- Clinical Trial
- Multicenter Study
PMID: 1969518 [PubMed - indexed for MEDLINE]
-
-
Blood pressure and mortality among men
with prior myocardial infarction. Multiple Risk Factor Intervention
Trial Research Group.
Flack JM, Neaton J, Grimm R Jr, Shih J, Cutler J, Ensrud
K, MacMahon S.
Hypertension Division, Bowman Gray School of Medicine, Winston-Salem, NC
27157-1032, USA.
BACKGROUND: The purpose of the present study was to describe the relation
between blood pressure (systolic [SBP] and diastolic [DBP]) and death from
coronary heart disease (CHD) and all causes for men with a history of myocardial
infarction (MI). METHODS AND RESULTS: The study cohort consisted of men aged
35 to 57 years screened for the Multiple Risk Factor Intervention Trial (MRFIT)
in 1973 through 1975 and followed for survival for an average of 16 years
through 1990. There were 5362 men who reported prior hospitalization for
a heart attack of at least 2 weeks' duration at the initial screening of
MRFIT. There was a J-shaped relation between SBP and DBP with both CHD and
all-cause mortality during the first 2 years of follow-up in older (age,
45 to 57 years) men only. Risk nadirs for SBP were 152 and 145 mm Hg, respectively,
for CHD death and all-cause mortality; corresponding DBP risk nadirs were
94 and 90 mm Hg. After the first 2 years, there was a positive association
between SBP and death from CHD and all causes. By 15 years, cumulative CHD
mortality percentages for men with screening SBP < 120, 120 to 139, 140
to 159, and > or = 160 mm Hg were 19.7%, 21.3%, 27.5%, and 32.0%, respectively.
When deaths only after year 2 were considered, although the linear DBP coefficient
was significant, the quadratic term for DBP was no longer significant (P > .05).
However, the relation still appeared J-shaped as cumulative mortality for
those with DBP < 70, 70 to 79, 80 to 89, 90 to 99, and > or = 100 mm
Hg was 24.3%, 20.8%, 21.1%, 25.5%, and 29.7%, respectively. When the joint
relation of SBP and DBP was considered, there were no survival differences
among the four cohorts (SBP > or = 140 and DBP < 80, SBP > or =
140 and DBP > or = 80, SBP < or = 140 and DBP < 80, and SBP < or
= 140 and DBP > or = 80) during the first 2 years. After 2 years, both
CHD and all-cause mortality rates were approximately 40% higher for participants
with SBP > or = 140 mm Hg versus < 140 mm Hg regardless of DBP level
(< 80 or > or = 80 mm Hg). CONCLUSIONS: In this large cohort of men
with prior MI, the association of SBP and DBP with CHD and all-cause mortality
varied over the 16-year follow-up period. During early follow-up, in older
men only, J- or U-shaped relations were evident. However, after 2 years,
these same relations had become positive and graded. Given the substantial
excess mortality risk in this cohort associated with high blood pressure,
particularly SBP, efforts to gradually lower blood pressure should receive
high priority among hypertensive men with prior MI.
Publication Types:
- Clinical Trial
- Multicenter Study
- Randomized Controlled Trial
PMID: 7586343 [PubMed - indexed for MEDLINE]
-
Prognostic significance of the electrocardiogram
after Q wave myocardial infarction. The Framingham Study.
Wong ND, Levy D, Kannel WB.
Department of Medicine, University of California, Irvine 92717.
The prognostic value of abnormalities on the electrocardiogram (ECG) present
1 year after initial myocardial infarction (MI) is examined in relation to
reinfarction and coronary death throughout 32 years (mean, 10.1 years) of
follow-up in the Framingham Heart Study. Resting 12-lead ECGs were available
in 251 survivors (190 men and 61 women) of clinically recognized Q wave MI.
The ECG reverted to normal in 31 (12.4%) cases and was abnormal but without
Q waves in 37 (14.7%). Q waves persisted without other significant abnormalities
in 108 (43.0%) and with other abnormalities in 75 (29.9%) cases. Electrocardiographic
abnormalities at follow-up were more common in women and in those persons
whose initial MI was anterior as compared with inferior. Nonspecific T wave,
ST segment changes, and electrocardiographic left ventricular hypertrophy
on the ECG before or after MI were powerful predictors (p less than 0.01)
of coronary death. The relation of these residual post-MI electrocardiographic
findings to reinfarction and coronary death was assessed by Cox regression
analysis. The follow-up electrocardiographic status was unrelated to the
risk of subsequent reinfarction. Subjects who lost Q wave evidence of MI
but whose ECG continued to show evidence of repolarization abnormalities,
left ventricular hypertrophy, or blocked intraventricular conduction were
at a 3.5-fold increased risk (p less than 0.01) of coronary death as compared
with those reverting to a normal ECG. Persons with a persistent Q wave MI
accompanied by these abnormalities were at a 2.7-fold excess risk (p = 0.01)
of coronary death as compared with those with a normalized ECG. These findings
remained significant when considering age and standard coronary risk factors.
The presence of other electrocardiographic abnormalities without persistent
Q waves yields a worse prognosis than a Q wave persisting alone. The prognostic
value of a follow-up ECG with abnormalities other than a persistent Q wave
MI also remained after considering the effects of left ventricular hypertrophy
and cardiac enlargement on x-ray, functional classification, and diuretic
usage. Specific electrocardiographic abnormalities present before infarction,
however, were potent indicators of long-term prognosis prognosis and diminished
the importance of the follow-up ECG. Although survival after initial MI is
improved only if the ECG reverts to normal, information on electrocardiographic
abnormalities before MI can be especially useful in evaluating long-term
risk.
PMID: 2306830 [PubMed - indexed for MEDLINE]-
Role of blood pressure in the development
of congestive heart failure. The Framingham study.
Kannel WB, Castelli WP, McNamara PM, McKee PA, Feinleib
M.
PMID: 4262573 [PubMed - indexed for MEDLINE]-
Hypertension and the brain. The National
High Blood Pressure Education Program.
Phillips SJ, Whisnant JP.
Department of Medicine (Division of Neurology), Dalhousie University Halifax,
Nova Scotia.
Neurogenic mechanisms are important in the maintenance of most forms of hypertension,
yet the brain is highly vulnerable to the deleterious effects of elevated
blood pressure. Hypertensive encephalopathy results from a sudden, sustained
rise in blood pressure sufficient to exceed the upper limit of cerebral blood
flow autoregulation. The cerebral circulation adapts to chronic less severe
hypertension but at the expense of changes that predispose to stroke due
to arterial occlusion or rupture. Stroke is a generic term for a clinical
syndrome that includes focal infarction or hemorrhage in the brain, or subarachnoid
hemorrhage. Atherothromboembolism and thrombotic occlusion of lipohyalinotic
small-diameter end arteries are the principal causes of cerebral infarction.
Microaneurysm rupture is the usual cause of hypertension-associated intracerebral
hemorrhage. Rupture of aneurysms on the circle of Willis is the most common
cause of nontraumatic subarachnoid hemorrhage. Stroke is a major cause of
morbidity and mortality, particularly among persons aged 65 years or older.
Treatment of diastolic hypertension reduces the incidence of stroke by about
40%. Treatment of isolated systolic hypertension in persons aged 60 years
and older reduces the incidence of stroke by more than one third. Blood pressure
management in the setting of acute stroke and the role of antihypertensive
therapy in the prevention of multi-infarct dementia require further study.
Publication Types:
PMID: 1580719 [PubMed - indexed for MEDLINE]
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Comment in:
15-year longitudinal study of blood pressure and
dementia.
Skoog I, Lernfelt B, Landahl S, Palmertz B, Andreasson
LA, Nilsson L, Persson G, Oden A, Svanborg A.
Department of Clinical Neurosciences, Sahlgrenska Hospital, Gothenburg,
Sweden.
BACKGROUND: Vascular causes of dementia may be more common than supposed.
Vascular factors may also have a role in late-onset Alzheimer's disease,
but the role of hypertension in the development of dementia is unclear.
METHODS: As part of the Longitudinal Population Study of 70-year-olds in
Goteborg, Sweden, we analysed the relation between blood pressure and the
development of dementia in the age intervals 70-75, 75-79, and 79-85 years
in those non-demented at age 70 (n = 382). The sample was followed up for
15 years and examined repeatedly with a comprehensive investigation, including
a psychiatric and physical examination. a FINDINGS: Participants who developed
dementia at age 79-85 had higher systolic blood pressure at age 70 (mean
178 vs 164 mm Hg, p = 0.034) and higher diastolic blood pressure at ages
70 (101 vs 92, p = 0.004) and 75 (97 vs 90, p = 0.022) than those who did
not develop dementia. For subtypes of dementia, higher diastolic blood
pressure was recorded at age 70 (101, p = 0.019) for those developing Alzheimer's
disease and at age 75 (101, p = 0.015) for those developing vascular dementia
than for those who did not develop dementia. Participants with white-matter
lesions on computed tomography at age 85 had higher blood pressure at age
70 than those without such lesions. Blood pressure declined in the years
before dementia onset and was then similar to or lower than that in non-demented
individuals. INTERPRETATION: Previously increased blood pressure may increase
the risk for dementia by inducing small-vessel disease and white-matter
lesions. To what extent the decline in blood pressure before dementia onset
is a consequence or a cause of the brain disease remains to be elucidated.
PMID: 8609748 [PubMed - indexed for MEDLINE]
22. Neal B, Clark T, MacMahon
S Blood pressure and the risk of recurrent vascular disease.
Am J Hypertens 1998; 11: 25A.
-
Coronary heart disease risk factors in
men and women aged 60 years and older: findings from the
Systolic Hypertension in the Elderly Program.
Frost PH, Davis BR, Burlando AJ, Curb JD, Guthrie GP, Isaacsohn
JL, Wassertheil-Smoller S, Wilson AC, Stamler J.
Cardiovascular Research Institute, University of California, San Francisco
94143-0326, USA. phf@itsa.ucsf.edu
BACKGROUND: Coronary heart disease (CHD) is the most common cause of death
in men and women aged 60 years and older. Although a number of studies support
the concept that CHD risk factors that have been defined in younger adults
are significantly associated with CHD events in older adults, others do not
support this thesis, and further definition of the risk-factor concept in
older adults is required. METHODS AND RESULTS: The Systolic Hypertension
in the Elderly Program recruited 4736 persons (mean age, 72 years); 14% were
black, and 43% were men. Mean systolic and diastolic blood pressures were
170 and 77 mm Hg, respectively. About 13% of participants were current smokers;
10% had a history of diabetes; 5%, a prior myocardial infarction; 5% angina
pectoris; 2.3%, intermittent claudication; and 7%, a carotid bruit. Mean
total cholesterol value was 6.11 mmol/L. Mean follow-up was 4.5 years. In
multivariate Cox regression analyses for CHD, variables that were significant
were baseline total cholesterol value, smoking, history of diabetes, presence
of carotid bruit, and treatment group in the trial. Active treatment yielded
a 27% reduction in CHD risk. For each 1.03 mmol/L increase in total cholesterol
value, there was an increase in risk of about 20%. Current smokers had a
73% increase, diabetics a 121% increase, and those with carotid bruit a 113%
increase in CHD risk. CONCLUSIONS: The results of this study support the
concept that CHD risk factors are important in older men and women with isolated
systolic hypertension.
PMID: 8964114 [PubMed - indexed for MEDLINE]
-
Comment in:
Carotid-artery intima and media thickness as a risk
factor for myocardial infarction and stroke in older adults. Cardiovascular
Health Study Collaborative Research Group.
O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL,
Wolfson SK Jr.
Department of Radiology, Tufts-New England Medical Center, Boston, MA,
USA. daniel.oleary@es.nemc.org
BACKGROUND: The combined thickness of the intima and media of the carotid
artery is associated with the prevalence of cardiovascular disease. We
studied the associations between the thickness of the carotid-artery intima
and media and the incidence of new myocardial infarction or stroke in persons
without clinical cardiovascular disease. METHODS: Noninvasive measurements
of the intima and media of the common and internal carotid artery were
made with high-resolution ultrasonography in 5858 subjects 65 years of
age or older. Cardiovascular events (new myocardial infarction or stroke)
served as outcome variables in subjects without clinical cardiovascular
disease (4476 subjects) over a median follow-up period of 6.2 years. RESULTS:
The incidence of cardiovascular events correlated with measurements of
carotid-artery intima-media thickness. The relative risk of myocardial
infarction or stroke increased with intima-media thickness (P<0.001).
The relative risk of myocardial infarction or stroke (adjusted for age
and sex) for the quintile with the highest thickness as compared with the
lowest quintile was 3.87 (95 percent confidence interval, 2.72 to 5.51).
The association between cardiovascular events and intima-media thickness
remained significant after adjustment for traditional risk factors, showing
increasing risks for each quintile of combined intima-media thickness,
from the second quintile (relative risk, 1.54; 95 percent confidence interval,
1.04 to 2.28), to the third (relative risk, 1.84; 95 percent confidence
interval, 1.26 to 2.67), fourth (relative risk, 2.01; 95 percent confidence
interval, 1.38 to 2.91), and fifth (relative risk, 3.15; 95 percent confidence
interval, 2.19 to 4.52). The results of separate analyses of myocardial
infarction and stroke paralleled those for the combined end point. CONCLUSIONS:
Increases in the thickness of the intima and media of the carotid artery,
as measured noninvasively by ultrasonography, are directly associated with
an increased risk of myocardial infarction and stroke in older adults without
a history of cardiovascular disease.
Publication Types:
PMID: 9878640 [PubMed - indexed for MEDLINE]
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Mortality over a period of 10 years in
patients with peripheral arterial disease.
Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR,
McCann TJ, Browner D.
Division of Epidemiology, University of California, San Diego, School of
Medicine, La Jolla 92093-0607.
BACKGROUND. Previous investigators have observed a doubling of the mortality
rate among patients with intermittent claudication, and we have reported
a fourfold increase in the overall mortality rate among subjects with large-vessel
peripheral arterial disease, as diagnosed by noninvasive testing. In this
study, we investigated the association of large-vessel peripheral arterial
disease with rates of mortality from all cardiovascular diseases and from
coronary heart disease. METHODS. We examined 565 men and women (average age,
66 years) for the presence of large-vessel peripheral arterial disease by
means of two noninvasive techniques--measurement of segmental blood pressure
and determination of flow velocity by Doppler ultrasound. We identified 67
subjects with the disease (11.9 percent), whom we followed prospectively
for 10 years. RESULTS. Twenty-one of the 34 men (61.8 percent) and 11 of
the 33 women (33.3 percent) with large-vessel peripheral arterial disease
died during follow-up, as compared with 31 of the 183 men (16.9 percent)
and 26 of the 225 women (11.6 percent) without evidence of peripheral arterial
disease. After multivariate adjustment for age, sex, and other risk factors
for cardiovascular disease, the relative risk of dying among subjects with
large-vessel peripheral arterial disease as compared with those with no evidence
of such disease was 3.1 (95 percent confidence interval, 1.9 to 4.9) for
deaths from all causes, 5.9 (95 percent confidence interval, 3.0 to 11.4)
for all deaths from cardiovascular disease, and 6.6 (95 percent confidence
interval, 2.9 to 14.9) for deaths from coronary heart disease. The relative
risk of death from causes other than cardiovascular disease was not significantly
increased among the subjects with large-vessel peripheral arterial disease.
After the exclusion of subjects who had a history of cardiovascular disease
at base line, the relative risks among those with large-vessel peripheral
arterial disease remained significantly elevated. Additional analyses revealed
a 15-fold increase in rates of mortality due to cardiovascular disease and
coronary heart disease among subjects with large-vessel peripheral arterial
disease that was both severe and symptomatic. CONCLUSIONS. Patients with
large-vessel peripheral arterial disease have a high risk of death from cardiovascular
causes.
PMID: 1729621 [PubMed - indexed for MEDLINE]-
Comment in:
Morbidity and mortality in hypertensive adults with
a low ankle/arm blood pressure index.
Newman AB, Sutton-Tyrrell K, Vogt MT, Kuller LH.
Department of Medicine, Medical College of Pennsylvania, Pittsburgh 15212.
OBJECTIVE--To evaluate the relationship between the ankle/arm blood pressure
index (AAI, the ratio of ankle to arm systolic blood pressure, a measure
of peripheral arterial disease) and short-term cardiovascular morbidity
and mortality in older adults with systolic hypertension. DESIGN--Prospective
cohort study, 1- to 2-year follow-up (mean, 16 months). SETTING--Eleven
of 16 field centers from the Systolic Hypertension in the Elderly Program.
PARTICIPANTS--1537 older men and women with systolic hypertension. MAIN
OUTCOME MEASURES--All-cause mortality, coronary heart disease (CHD) mortality,
cardiovascular disease (CVD) mortality, and CHD and CVD morbidity and mortality.
RESULTS--The AAI was measured at the 1989-1990 clinic examination and was
0.9 or less in 25.5% of 1537 participants. A low AAI was associated with
most major CHD and CVD risk factors. In those with a low AAI (< or =
0.9) compared with those with an AAI of more than 0.9, age- and sex-adjusted
relative risks for mortality end points at follow-up were as follows: total
mortality, 3.8 (95% confidence interval [CI], 2.1 to 6.9); CHD mortality,
3.24 (95% CI, 1.4 to 7.5); and CVD mortality, 3.7 (95% CI, 1.8 to 7.7).
For CVD morbidity and mortality, the age- and sex-adjusted relative risk
was 2.5 (95% CI, 1.5 to 4.3). After adjustment for baseline CVD and other
cardiovascular risk factors, the relative risk for total mortality was
4.1 (95% CI, 2.0 to 8.3) and for CVD morbidity and mortality, 2.4 (95%
CI, 1.3 to 4.4). Results were similar when participants with clinical CVD
at baseline were excluded. CONCLUSION--A low AAI appears to be an important
predictor of morbidity and mortality among older adults with systolic hypertension.
PMID: 8147959 [PubMed - indexed for MEDLINE]
-
Does non-malignant essential hypertension
cause renal damage? A clinician's view.
Beevers DG, Lip GY.
University Department of Medicine, City Hospital, Birmingham, UK.
Clinical research amongst hypertensive patients, randomised controlled trials,
and population studies confined to white communities all show scant evidence
that 'essential' non-malignant non-proteinuric normo-creatininaemic hypertension
leads to renal impairment. Retrospective data from dialysis and transplantation
units also tend to confirm this point. The only convincing exception is in
studies of African Americans where there does appear to be a relationship
between blood pressure (BP) at screening and the subsequent development of
renal impairment. However, it is not possible to be certain that those patients
who develop renal impairment might not have had a low grade sub clinical
glomerulonephritis when first seen. One must conclude, therefore, that if
benign essential hypertension does damage the kidneys, it does so very rarely.
In that respect the epidemiology of hypertension-induced renal damage is
different from that of coronary heart disease and stroke. Additional and
novel risk factors need to be sought.
Publication Types:
PMID: 9004097 [PubMed - indexed for MEDLINE]
28. Samuelsson O, Wilhelmsson
L, Elmfeldt D et al. Predictors of cardiovascular morbidity in
treated hypertension: results from the Primary Preventive Trial
in Göteborg, Sweden. J Hypertens 1985; 3: 167–176.
The survival of treated hypertensive patients
and their causes of death: a report from the DHSS hypertensive
care computing project (DHCCP).
Bulpitt CJ, Beevers DG, Butler A, Coles EC, Hunt D, Munro-Faure
AD, Newson RB, O'Riordan PW, Petrie JC, Rajagopalan B, et al.
A prospective study has been carried out to determine the causes of death
and risk factors for survival in 4994 patients referred with a diagnosis
of hypertension to hospital specialist clinics and 457 patients treated by
their general practitioners for this condition. At the time of entering the
prospective study, 69% of the patients were already being treated for hypertension.
Four hundred and eleven patients have died, and their causes of death and
death rates have been compared with the rates for the population of England
and Wales. Ischaemic heart disease accounted for over one-third of the deaths
and stroke for one-fifth. The death rates for these conditions were two to
five times those expected for men and women aged 50-59 years and up to twice
the rate expected for the age group 60-69 years. Survival in these selected
patients was impaired by the following independent risk indicators: cigarette
smoking, previous history of myocardial infarction or stroke, diagnosis of
angina, impaired renal function and raised blood sugar. The following factors
were not independent positive risk factors: smoking a pipe or cigars, obesity,
a low plasma potassium and an elevated serum uric acid.
PMID: 3958486 [PubMed - indexed for MEDLINE]-
Complications and survival of 315 patients
with malignant-phase hypertension.
Lip GY, Beevers M, Beevers DG.
University Department of Medicine, City Hospital, Birmingham, UK.
OBJECTIVE: To investigate the factors affecting survival in patients with
malignant hypertension by analysing the prognosis of all of the patients
referred to the City Hospital, Birmingham, with malignant hypertension since
1965. RESULTS: We identified 315 patients with malignant hypertension (211
men, 104 women; mean age +/- SD 49.4 +/- 12.7 years). Of those patients,
219 were Caucasian, 55 were black and 41 were Asian. Black patients had greater
renal impairment and higher blood pressures at presentation. After a median
follow-up period of 33 months (range 1-389), 126 patients (40.0%) were still
alive, 126 patients (40.0%) were dead, 10 patients (3.2%) were receiving
chronic haemodialysis and 53 patients (16.8%) were lost to follow-up. Mean
follow-up blood pressures in the patients who died were significantly higher
than in those who lived. Median survival times for Caucasian, black and Asian
patients were 121.0, 30.4 and 107.5 months, respectively, with the lowest
survival time being that of black patients. There was a lower median survival
time among patients with proteinuria and high serum urea (> 10 mmol/l)
and creatinine (> 200 mumol/l) levels at presentation and if left ventricular
hypertrophy was detected on the electrocardiogram, but there was no difference
in median survival time between those with and without haematuria, nor between
non-smokers and current or former smokers. The most common causes of death
were renal failure (39.7%), stroke (23.8%), myocardial infarction (11.1%)
and heart failure (10.3%). Median survival times for the patients who presented
before 1970, during 1970-1979 and during 1980-1989 were 39.2, 68.6 and 144.0+
months, respectively, demonstrating an improved survival time for the patients
who were diagnosed after 1980. Using multivariate Cox's proportional hazards
analyses, the duration of known hypertension and serum urea level at presentation
were found to be the main predictors of survival. CONCLUSION: Malignant hypertension
remains a disease with a poor overall prognosis, namely progression to death
or chronic renal haemodialysis. The prognosis has improved with recent advances
in therapy, with a 5-year survival of 74% of patients. The poor outlook for
black patients could be explained by their late presentation with severe
hypertension and the higher prevalence of renal impairment in this group.
PMID: 8557970 [PubMed - indexed for MEDLINE]-
Microalbuminuria as predictor of vascular
disease in non-diabetic subjects. Islington Diabetes Survey.
Yudkin JS, Forrest RD, Jackson CA.
Department of Medicine, University College and Middlesex School of Medicine,
Whittington Hospital, London.
The relation between urinary albumin excretion rate (AER) and vascular disease
was studied in 187 subjects aged over 40 selected from 1084 cases attending
a diabetic screening project. AER exceeded 20 micrograms/min in 3 of 13 newly
diagnosed diabetic subjects (23%) and 16 of 171 non-diabetic subjects (9.4%).
There was a weak relation between AER and both systolic and diastolic blood
pressures. Coronary heart disease was found in 54 of 164 (32.9%) subjects
with AER of 20 micrograms/min or less and in 14 of 19 (74%) with AER above
this. Peripheral vascular disease was present in 16 of 165 (9.7%) subjects
with AER of 20 micrograms/min or less and 8 of 18 (44%) with a high AER.
Logistic regression, including diabetes, impaired glucose tolerance, systolic
and diastolic blood pressures, smoking, age, sex, ethnic origin, and body
mass index, demonstrated the independence of this relation between AER above
20 micrograms/min and coronary heart disease (odds ratio [OR] 6.38, 95% confidence
interval 1.91-21.4) and peripheral vascular disease (OR 7.72, 2.14-27.8).
After a mean of 3.6 (SD 0.19) years, 167 subjects (89.3%) were traced. There
had been 9 deaths, 3 (2.0%) among 149 subjects with normal AER and 6 (33%)
among 18 microalbuminuric subjects (OR 24.33, 5.40-109.7).
PMID: 2900920 [PubMed - indexed for MEDLINE]-
Microalbuminuria screening by reagent
strip predicts cardiovascular risk in hypertension.
Agrawal B, Berger A, Wolf K, Luft FC.
Boehringer Mannheim GmbH, Germany.
OBJECTIVE: We tested the hypothesis that qualitative microalbuminuria (MAU)
screening in a practice setting would identify non-diabetic hypertensive
patients at high risk of developing cardiovascular disease. DESIGN: We enrolled
general practitioners throughout Germany, who obtained histories, physical
examinations, and routine laboratory values as clinically indicated on treated
or non-treated hypertensive, non-diabetic patients. MAU was measured with
a albumin-sensitive, immunoassay test strip. We studied 11 343 non-diabetic
hypertensive patients. RESULTS: The patients' mean age was 57 years, 51%
were men and mean hypertension duration was 69 months. Twenty-five per cent
had coronary artery disease, 17% had left ventricular hypertrophy, 5% had
had a stroke, and 6% had peripheral vascular disease. MAU was present in
32% of men and 28% of women (P < 0.05). In patients with MAU, 31% had
coronary artery disease, 24% had left ventricular hypertrophy, 6% had had
a stroke, and 7% had peripheral vascular disease. In patients without MAU,
these rates were 22%, 14%, 4%, and 5% respectively: lower in every category
(P < 0.001). Further, in patients with coronary artery disease, left ventricular
hypertrophy, stroke, and peripheral vascular disease, MAU was significantly
greater than in patients who did not have these complications (P < 0.001).
MAU increased with age, severity of hypertension and duration of hypertension,
was associated with higher plasma creatinine values, and was more common
in patients with hyperlipidemia (P < 0.05). CONCLUSION: On the basis of
our survey, we conclude that qualitative MAU determinations identify hypertensive
patients with particular cardiovascular risk in a practice setting.
PMID: 8728300 [PubMed - indexed for MEDLINE]-
Comment in:
Microalbuminuria and endothelial dysfunction in
essential hypertension.
Pedrinelli R, Giampietro O, Carmassi F, Melillo E, Dell'Omo
G, Catapano G, Matteucci E, Talarico L, Morale M, De Negri
F, et al.
Clinica Medica 1, University of Pisa, Italy.
Microalbuminuria (urinary albumin excretion between 20 and 200 micrograms/min)
and endothelial dysfunction coexist in patients with essential hypertension.
To evaluate whether the two phenomena are related and the determinants
of that association, we recruited 10 untreated males with essential hypertension
and microalbuminuria without diabetes to be compared with an equal number
of matched patients with essential hypertension excreting albumin in normal
amounts and 10 normal controls. The status of endothelial function was
inferred from circulating von Willebrand Factor antigen (vWF), a glycoprotein
secreted in greater amounts when the vascular endothelium is damaged. vWF
concentrations were higher in hypertensive patients with microalbuminuria
than in hypertensive patients without and controls. Individual vWF and
urine albumin-excretion values were correlated (r = 0.55, p < 0.002).
Blood pressure correlated with both urinary albumin excretion and vWF.
Left ventricular mass index and minimal forearm vascular resistances were
comparable in patients with hypertension and higher than in controls; total
and low-density lipoprotein cholesterol, triglycerides, lipoprotein-a,
Factor VII, and plasminogen activator inhibitor-1 did not differ. Fibrinogen
was higher and creatinine clearance lower in microalbuminurics. Albuminuria
in essential hypertension may reflect systemic dysfunction of the vascular
endothelium, a structure intimately involved in permeability, haemostasis,
fibrinolysis, and blood pressure control. This abnormality may have important
physiopathological implications and expose these patients to increased
cardiovascular risk.
PMID: 7912295 [PubMed - indexed for MEDLINE]
-
Some different types of essential hypertension:
their course and prognosis.
Keith NM, Wagener HP, Barker NW.
Publication Types:
- Biography
- Historical Article
Personal Name as Subject:
- Keith NM
- Wagener HP
- Barker NW
Hypertensive retinopathy: a review of
existing classification systems and a suggestion for a simplified
grading system.
Dodson PM, Lip GY, Eames SM, Gibson JM, Beevers DG.
Department of Medicine, Heartlands Hospital, Birmingham, UK.
With the advent of sophisticated ophthalmological investigations and a better
understanding of the pathophysiology and clinical or prognostic correlates
of the fundal lesions in hypertension, the limitations of early classification
schemes using simple ophthalmoscopic appearances are increasingly apparent.
This review describes the existing classification systems for hypertensive
retinopathy and their limitations, as well as the pathophysiological effects
of hypertension on the retinal vasculature. A new and simpler grading system
for hypertensive retinopathy is proposed, dividing the features according
to prognosis into two categories of non-malignant vs malignant hypertension.
Such a simpler, updated system for our medical practice has been long overdue.
Publication Types:
PMID: 8867562 [PubMed - indexed for MEDLINE]
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