Everywhere we turn today, we are bombarded with advertisements and public
health announcements about hypertension, high blood pressure. It should come
as no surprise that this a major public health problem. The effects of hypertension
are felt throughout every organ system in the human body. Fortunately, with
early detection, many cases can be controlled and the long term devastating
effects mitigated.
Hypertension is a broad disease with both primary and secondary causes. Primary
hypertension is also referred to as essential hypertension. Secondary causes
of hypertension are diverse. A partial list is given below.
| EPIDEMIOLOGY |
CHARACTERIZATION |
| INCIDENCE |
Prevalence increases with age |
|
Hypertension prevalence and blood pressure levels in 6 European countries,
Canada, and the United States.
Wolf-Maier K, Cooper RS, Banegas JR, Giampaoli S, Hense HW,
Joffres M, Kastarinen M, Poulter N, Primatesta P, Rodriguez-Artalejo
F, Stegmayr B, Thamm M, Tuomilehto J, Vanuzzo D, Vescio F.
Department of Preventive Medicine and Epidemiology, Loyola
University Stritch School of Medicine, Maywood, Ill.
|
JAMA 2003 May 14;289(18):2363-9 Abstract quote
CONTEXT: Geographic variations in cardiovascular disease (CVD) and
associated risk factors have been recognized worldwide. However, little
attention has been directed to potential differences in hypertension
between Europe and North America.
OBJECTIVE: To determine whether higher blood pressure (BP) levels and
hypertension are more prevalent in Europe than in the United States
and Canada.
DESIGN, SETTING, AND PARTICIPANTS: Sample surveys that were national
in scope and conducted in the 1990s were identified in Germany, Finland,
Sweden, England, Spain, Italy, Canada, and the United States. Collaborating
investigators provided tabular data in a consistent format by age and
sex for persons at least 35 years of age. Population registries were
the main basis for sampling. Survey sizes ranged from 1800 to 23 100,
with response rates of 61% to 87.5%. The data were analyzed to provide
age-specific and age-adjusted estimates of BP and hypertension prevalence
by country and region (eg, European vs North American).
MAIN OUTCOME MEASURES: Blood pressure levels and prevalence of hypertension
in Europe, the United States, and Canada.
RESULTS: Average BP was 136/83 mm Hg in the European countries and 127/77
mm Hg in Canada and the United States among men and women combined who
were 35 to 74 years of age. This difference already existed among younger
persons (35-39 years) in whom treatment was uncommon (ie, 124/78 mm
Hg and 115/75 mm Hg, respectively), and the slope with age was steeper
in the European countries. For all age groups, BP measurements were
lowest in the United States and highest in Germany. The age- and sex-adjusted
prevalence of hypertension was 28% in the North American countries and
44% in the European countries at the 140/90 mm Hg threshold. The findings
for men and women by region were similar. Hypertension prevalence was
strongly correlated with stroke mortality (r = 0.78) and more modestly
with total CVD (r = 0.44).
CONCLUSIONS: Despite extensive research on geographic patterns of CVD,
the 60% higher prevalence of hypertension in Europe compared with the
United States and Canada has not been generally appreciated. The implication
of this finding for national prevention strategies should be vigorously
explored.
|
| EPIDEMIOLOGIC ASSOCIATIONS |
Blacks twice as common as whites |
| LABORATORY/RADIOLOGIC/
OTHER TESTS |
CHARACTERIZATION |
| RADIOLOGIC |
|
| LABORATORY MARKERS |
|
| ANGIOTENSIN CONVERTING ENZYME |
|
Angiotensin converting enzyme DD genotype is associated with hypertensive
crisis.
Sunder-Plassmann G, Kittler H, Eberle C, Hirschl MM, Woisetschlager
C, Derhaschnig U, Laggner AN, Horl WH, Fodinger M.
Department of Medicine III, University of Vienna, Austria.
|
Crit Care Med 2002 Oct;30(10):2236-41 Abstract quote
OBJECTIVE: The genetic background of hypertensive crisis is unknown.
We examined the association of polymorphisms in genes involved in the
renin-angiotensin-aldosterone-system with hypertensive crisis.
DESIGN: Population-based case-control study.
SETTING: Emergency department at a tertiary care university hospital.
PATIENTS: A total of 182 patients with essential hypertension who were
admitted to an emergency department for treatment of hypertensive crisis
and 182 age- and sex-matched healthy individuals.
INTERVENTIONS: None.
MEASUREMENTS: Analysis of polymorphisms in genes coding for angiotensinogen
(AJT 704T-->C), angiotensin II receptor 1 (AGTR1 1166A-->C), renin
(REN 2646G-->A), renin-binding protein (RENBP 61T-->C), alpha-adducin
(ADD1 1378G-->T), beta-2-adrenergic receptor (ADRB2 46A-->G, 79C-->G),
and angiotensin I converting enzyme (ACE I/D) was performed by polymerase
chain reaction and restriction fragment length polymorphism analysis.
MAIN RESULTS Among patients, the ACE I/D polymorphism showed a deviation
from Hardy-Weinberg equilibrium (p =.01). In controls, all polymorphisms
were in the Hardy-Weinberg equilibrium. The frequency of the DD genotype
was increased in patients (n = 70, 38.5%) vs. controls (n = 51; 28.0%;p
=.03; odds ratio, 1.61; 95% confidence interval, 1.03-2.50), which was
due to the DD genotype in 40 male patients (44%) vs. 23 in male controls
(25.3%;p =.004; odds ratio, 3.48; 95% confidence interval, 1.47-8.30).
There were no differences in genotype distributions among other polymorphisms.
CONCLUSION: We demonstrate a possible association of the DD genotype
with hypertensive crisis in men. |
| C REACTIVE PROTEIN |
|
C-reactive protein and the risk of developing hypertension.
Sesso HD, Buring JE, Rifai N, Blake GJ, Gaziano JM, Ridker PM.
Department of Medicine, Center for Cardiovascular Disease Prevention and the Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass 02215-1204, USA.
|
| JAMA. 2003 Dec 10;290(22):2945-51. Abstract quote |
|
CONTEXT: Although it has been hypothesized that hypertension is in part an inflammatory disorder, clinical data linking inflammation with incident hypertension are scarce.
OBJECTIVE: To examine whether C-reactive protein levels, a marker of systemic inflammation, are associated with incident hypertension.
DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood samples with initially normal levels of blood pressure (BP) (systolic BP <140 mm Hg and diastolic BP <90 mm Hg, and no history of hypertension or antihypertensive medications) and then followed up for a median of 7.8 years for the development of incident hypertension. Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected. MAIN OUTCOME MEASURE: Incident hypertension, defined as either a new physician diagnosis, the initiation of antihypertensive treatment, or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg.
RESULTS: During follow-up, 5365 women developed incident hypertension. In crude models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing hypertension from the lowest (referent) to the highest levels of baseline C-reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68), 1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P<.001). In fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.95-1.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.36-1.69) (linear trend P<.001). C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated, including those with very low levels of baseline BP, as well as those with no traditional coronary risk factors. Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP.
CONCLUSION: C-reactive protein levels are associated with future development of hypertension, which suggests that hypertension is in part an inflammatory disorder.
|
GROSS APPEARANCE/
CLINICAL VARIANTS |
CHARACTERIZATION |
| GENERAL |
|
The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo
JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ.
Department of Medicine, Boston University School of Medicine,
Boston, Mass.
|
JAMA 2003 May 21;289(19):2560-71 Abstract quote "The Seventh
Report of the Joint National Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure" provides a new guideline
for hypertension prevention and management.
The following are the key messages(1) In persons older than 50 years,
systolic blood pressure (BP) of more than 140 mm Hg is a much more important
cardiovascular disease (CVD) risk factor than diastolic BP; (2) The
risk of CVD, beginning at 115/75 mm Hg, doubles with each increment
of 20/10 mm Hg; individuals who are normotensive at 55 years of age
have a 90% lifetime risk for developing hypertension; (3) Individuals
with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89
mm Hg should be considered as prehypertensive and require health-promoting
lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics
should be used in drug treatment for most patients with uncomplicated
hypertension, either alone or combined with drugs from other classes.
Certain high-risk conditions are compelling indications for the initial
use of other antihypertensive drug classes (angiotensin-converting enzyme
inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel
blockers); (5) Most patients with hypertension will require 2 or more
antihypertensive medications to achieve goal BP (<140/90 mm Hg, or
<130/80 mm Hg for patients with diabetes or chronic kidney disease);
(6) If BP is more than 20/10 mm Hg above goal BP, consideration should
be given to initiating therapy with 2 agents, 1 of which usually should
be a thiazide-type diuretic; and (7)
The most effective therapy prescribed by the most careful clinician
will control hypertension only if patients are motivated. Motivation
improves when patients have positive experiences with and trust in the
clinician. Empathy builds trust and is a potent motivator. Finally,
in presenting these guidelines, the committee recognizes that the responsible
physician's judgment remains paramount.
|
| VARIANTS |
|
| MALIGNANT HYPERTENSION |
|
|
Continuing follow-up of malignant hypertension.
Scarpelli PT, Gallo M, De Cesaris F, Chiari G, Dedola G, Cappeli
S, Becucci A, Becherelli P, Tosi B, Fanetti C, Fanelli R.
Postgraduate School of Nephrology, University of Florence,
Italy. |
J Nephrol 2002 Jul-Aug;15(4):431-7 Abstract quote
The history of accelerated (malignant) hypertension is reviewed, and
unsolved problems related to the disease are illustrated, including
its relationship to malignant nephrosclerosis, as well as terminology,
current frequency and treatment.
Over the past 25 years, out of a series of 131 patients, 53 were classified
as suffering from essential malignant hypertension, the only suitable
model on which the effects of pharmacological treatment on the disease
can correctly be evaluated. In 2000, there were 24 survivors in our
series and the maximum follow-up was 290 months.
Multiple daily B.P. self-measurements allowed us to establish that
pharmacological treatment was only able to approximate, to a varying
degree, the conventional threshold of 140/90. Yet, despite this incomplete
control over blood pressure levels, renal function was maintained in
those patients whose initial creatininemia levels had not been higher
than 2 mg/L.
The renal protection effect of treatment was preserved even in patients
who relapsed intoaccelerated disease phase one or more times over the
study period. |
Accelerated (malignant) hypertension: a study of 121 cases between 1974
and 1996.
Scarpelli PT, Livi R, Caselli GM, Di Maria L, Teghini L, Montemurro
V, Toti G, Becucci A.
Postgraduate School of Nephrology, Institute of Clinical Medicine
IV, University of Florence, Italy. |
J Nephrol 1997 Jul-Aug;10(4):207-15 Abstract quote
A series of 121 consecutive cases with accelerated hypertension is
presented. Forty-seven patients had essential hypertension. This diagnosis
was confirmed during the follow-up, which lasted from 3 to 255 months
(mean 63.1 +/- 58.1).
The relationship between the effects of pharmacological treatment on
high blood pressure (BP) and disease course were analyzed in accelerated
essential hypertensive patients only, to avoid the imponderable influence
of basic disease in secondary hypertension. In most cases, therapeutical
effect on BP was monitored by multiple daily BP self-measurements.
Since 1974, when this study was initiated, plasma creatinine concentration
at admission showed a clear-cut decrease, especially after the introduction
in the eighties of new hypotensive drugs. A sustained BP decrease assured
a long-lasting preservation of renal function, if the initial functional
loss was limited (plasma creatinine concentration of 2 mg/dl (176.8
mumol/l) or less). Renal function was preserved even if the BP decrease
was not optimal and signs of relapsing malignant retinopathy were observed
in the course of disease.
Although the whole series showed a 12-year survival rate of about 69%,
patients enrolled after 1980 had a 100% survival rate.
|
| PROGNOSIS AND TREATMENT |
CHARACTERIZATION |
| PROGNOSTIC FACTORS |
|
| LEFT VENTRICULAR MASS |
|
-
Prognostic significance of left ventricular mass change during treatment of hypertension.
Devereux RB, Wachtell K, Gerdts E, Boman K, Nieminen MS, Papademetriou V, Rokkedal J, Harris K, Aurup P, Dahlof B.
Department of Medicine, New York Presbyterian Hospital, Cornell Medical Center, New York, NY 10021, USA.
|
-
| JAMA. 2004 Nov 17;292(19):2350-6. Abstract quote |
|
CONTEXT: Increased baseline left ventricular (LV) mass predicts cardiovascular (CV) complications of hypertension, but the relation between lower LV mass and outcome during treatment for hypertension is uncertain.
OBJECTIVE: To determine whether reduction of LV mass during antihypertensive treatment modifies risk of major CV events independent of blood pressure change.
DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort substudy of the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) randomized clinical trial, conducted from 1995 to 2001. A total of 941 prospectively identified patients aged 55 to 80 years with essential hypertension and electrocardiographic LV hypertrophy had LV mass measured by echocardiography at enrollment in the LIFE trial and thereafter were followed up annually for a mean (SD) of 4.8 (1.0) years for CV events.
MAIN OUTCOME MEASURES: Composite end point of CV death, fatal or nonfatal myocardial infarction, and fatal or nonfatal stroke.
RESULTS: The composite end point occurred in 104 patients (11%). The multivariable Cox regression model showed a strong association between lower in-treatment LV mass index and reduced rate of the composite CV end point (hazard ratio [HR], 0.78 per 1-SD (25.3) decrease in LV mass index; 95% confidence interval [CI], 0.65-0.94; P = .009) over and above that predicted by reduction in blood pressure. There were parallel associations between lower in-treatment LV mass index and lower CV mortality (HR, 0.62; 95% CI, 0.47-0.82; P = .001), stroke (HR, 0.76; 95% CI, 0.60-0.96; P = .02), myocardial infarction (HR, 0.85; 95% CI, 0.62-1.17, P = .33), and all-cause mortality (HR, 0.72; 95% CI, 0.59-0.88, P = .002), independent of systolic blood pressure and assigned treatment. Results were confirmed in analyses adjusting for additional CV risk factors, electrocardiographic changes, or when only considering events after the first year of study treatment.
CONCLUSION: In patients with essential hypertension and baseline electrocardiographic LV hypertrophy, lower LV mass during antihypertensive treatment is associated with lower rates of clinical end points, additional to effects of blood pressure lowering and treatment modality.
|
| PREVENTION |
|
|
Trends in prevalence, awareness, treatment, and control of hypertension
in the United States, 1988-2000.
Hajjar I, Kotchen TA.
Division of Geriatrics, Department of Medicine, Palmetto Health
Richland, University of South Carolina, Columbia, USA. |
JAMA. 2003 Jul 9;290(2):199-206. Abstract quote CONTEXT: Prior analyses
of National Health and Nutrition Examination Survey (NHANES) data through
1991 have suggested that hypertension prevalence is declining, but more
recent self-reported rates of hypertension suggest that the rate is
increasing.
OBJECTIVE: To describe trends in the prevalence, awareness, treatment,
and control of hypertension in the United States using NHANES data.
DESIGN, SETTING, AND PARTICIPANTS: Survey using a stratified multistage
probability sample of the civilian noninstitutionalized population.
The most recent NHANES survey, conducted in 1999-2000 (n = 5448), was
compared with the 2 phases of NHANES III conducted in 1988-1991 (n =
9901) and 1991-1994 (n = 9717). Individuals aged 18 years or older were
included in this analysis.
MAIN OUTCOME MEASURES: Hypertension, defined as a measured blood pressure
of 140/90 mm Hg or greater or reported use of antihypertensive medications.
Hypertension awareness and treatment were assessed with standardized
questions. Hypertension control was defined as treatment with antihypertensive
medication and a measured blood pressure of less than 140/90 mm Hg.
RESULTS: In 1999-2000, 28.7% of NHANES participants had hypertension,
an increase of 3.7% (95% confidence interval [CI], 0%-8.3%) from 1988-1991.
Hypertension prevalence was highest in non-Hispanic blacks (33.5%),
increased with age (65.4% among those aged > or =60 years), and tended
to be higher in women (30.1%). In a multiple regression analysis, increasing
age, increasing body mass index, and non-Hispanic black race/ethnicity
were independently associated with increased rates of hypertension.
Overall, in 1999-2000, 68.9% were aware of their hypertension (nonsignificant
decline of -0.3%; 95% CI, -4.2% to 3.6%), 58.4% were treated (increase
of 6.0%; 95% CI, 1.2%-10.8%), and hypertension was controlled in 31.0%
(increase of 6.4%; 95% CI, 1.6%-11.2%). Women, Mexican Americans, and
those aged 60 years or older had significantly lower rates of control
compared with men, younger individuals, and non-Hispanic whites.
CONCLUSIONS: Contrary to earlier reports, hypertension prevalence is
increasing in the United States. Hypertension control rates, although
improving, continue to be low. Programs targeting hypertension prevention
and treatment are of utmost importance. |
| TREATMENT |
|
| LIFESTYLE CHANGES |
|
|
Effects of Comprehensive Lifestyle Modification on Blood Pressure Control:
Main Results of the PREMIER Clinical Trial.
Writing Group Of The PREMIER Collaborative Research Group.
Departments of Medicine, Epidemiology, and International Health,
Johns Hopkins Medical Institutions, Baltimore, Md.
|
JAMA 2003 Apr 23;289(16):2083-93 Abstract quote
CONTEXT: Weight loss, sodium reduction, increased physical activity,
and limited alcohol intake are established recommendations that reduce
blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH)
diet also lowers BP. To date, no trial has evaluated the effects of
simultaneously implementing these lifestyle recommendations.
OBJECTIVE: To determine the effect on BP of 2 multicomponent, behavioral
interventions.
DESIGN, SETTING, AND PARTICIPANTS: Randomized trial with enrollment
at 4 clinical centers (January 2000-June 2001) among 810 adults (mean
[SD] age, 50 [8.9] years; 62% women; 34% African American) with above-optimal
BP, including stage 1 hypertension (120-159 mm Hg systolic and 80-95
mm Hg diastolic), and who were not taking antihypertensive medications.
INTERVENTION: Participants were randomized to one of 3 intervention
groups: (1) "established," a behavioral intervention that
implemented established recommendations (n = 268); (2) "established
plus DASH,"which also implemented the DASH diet (n = 269); and
(3) an "advice only" comparison group (n = 273).
MAIN OUTCOME MEASURES: Blood pressure measurement and hypertension
status at 6 months.
RESULTS: Both behavioral interventions significantly reduced weight,
improved fitness, and lowered sodium intake. The established plus DASH
intervention also increased fruit, vegetable, and dairy intake. Across
the groups, gradients in BP and hypertensive status were evident. After
subtracting change in advice only, the mean net reduction in systolic
BP was 3.7 mm Hg (P<.001) in the established group and 4.3 mm Hg
(P<.001) in the established plus DASH group; the systolic BP difference
between the established and established plus DASH groups was 0.6 mm
Hg (P =.43). Compared with the baseline hypertension prevalence of 38%,
the prevalence at 6 months was 26% in the advice only group, 17% in
the established group (P =.01 compared with the advice only group),
and 12% in the established plus DASH group (P<.001 compared with
the advice only group; P =.12 compared with the established group).
The prevalence of optimal BP (<120 mm Hg systolic and <80 mm Hg
diastolic) was 19% in the advice only group, 30% in the established
group (P =.005 compared with the advice only group), and 35% in the
established plus DASH group (P<.001 compared with the advice only
group; P =.24 compared with the established group).
CONCLUSION: Individuals with above-optimal BP, including stage 1 hypertension,
can make multiple lifestyle changes that lower BP and reduce their cardiovascular
disease risk.
|
| STATIN THERAPY |
|
|
Major outcomes in moderately hypercholesterolemic, hypertensive patients
randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative
Research Group. The Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial.
|
JAMA 2002 Dec 18;288(23):2998-3007 Abstract quote
CONTEXT: Studies have demonstrated that statins administered to individuals
with risk factors for coronary heart disease (CHD) reduce CHD events.
However, many of these studies were too small to assess all-cause mortality
or outcomes in important subgroups. OBJECTIVE: To determine whether
pravastatin compared with usual care reduces all-cause mortality in
older, moderately hypercholesterolemic, hypertensive participants with
at least 1 additional CHD risk factor.
DESIGN AND SETTING: Multicenter (513 primarily community-based North
American clinical centers), randomized, nonblinded trial conducted from
1994 through March 2002 in a subset of participants from the Antihypertensive
and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
PARTICIPANTS: Ambulatory persons (n = 10 355), aged 55 years or older,
with low-density lipoprotein cholesterol (LDL-C) of 120 to 189 mg/dL
(100 to 129 mg/dL if known CHD) and triglycerides lower than 350 mg/dL,
were randomized to pravastatin (n = 5170) or to usual care (n = 5185).
Baseline mean total cholesterol was 224 mg/dL; LDL-C, 146 mg/dL; high-density
lipoprotein cholesterol, 48 mg/dL; and triglycerides, 152 mg/dL. Mean
age was 66 years, 49% were women, 38% black and 23% Hispanic, 14% had
a history of CHD, and 35% had type 2 diabetes.
INTERVENTION: Pravastatin, 40 mg/d, vs usual care.
MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality,
with follow-up for up to 8 years. Secondary outcomes included nonfatal
myocardial infarction or fatal CHD (CHD events) combined, cause-specific
mortality, and cancer.
RESULTS: Mean follow-up was 4.8 years. During the trial, 32% of usual
care participants with and 29% without CHD started taking lipid-lowering
drugs. At year 4, total cholesterol levels were reduced by 17% with
pravastatin vs 8% with usual care; among the random sample who had LDL-C
levels assessed, levels were reduced by 28% with pravastatin vs 11%
with usual care. All-cause mortality was similar for the 2 groups (relative
risk [RR], 0.99; 95% confidence interval [CI], 0.89-1.11; P =.88), with
6-year mortality rates of 14.9% for pravastatin vs 15.3% with usual
care. CHD event rates were not significantly different between the groups
(RR, 0.91; 95% CI, 0.79-1.04; P =.16), with 6-year CHD event rates of
9.3% for pravastatin and 10.4% for usual care.
CONCLUSIONS: Pravastatin did not reduce either all-cause mortality
or CHD significantly when compared with usual care in older participants
with well-controlled hypertension and moderately elevated LDL-C. The
results may be due to the modest differential in total cholesterol (9.6%)
and LDL-C (16.7%) between pravastatin and usual care compared with prior
statin trials supporting cardiovascular disease prevention.
|
| THIAZIDES |
|
Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting
enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive
and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative
Research Group. The Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial.
|
JAMA 2002 Dec 18;288(23):2981-97 Abstract quote
CONTEXT: Antihypertensive therapy is well established to reduce hypertension-related
morbidity and mortality, but the optimal first-step therapy is unknown.
OBJECTIVE: To determine whether treatment with a calcium channel blocker
or an angiotensin-converting enzyme inhibitor lowers the incidence of
coronary heart disease (CHD) or other cardiovascular disease (CVD) events
vs treatment with a diuretic.
DESIGN: The Antihypertensive and Lipid-Lowering Treatment to Prevent
Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled
clinical trial conducted from February 1994 through March 2002.
SETTING AND PARTICIPANTS: A total of 33 357 participants aged 55 years
or older with hypertension and at least 1 other CHD risk factor from
623 North American centers.
INTERVENTIONS: Participants were randomly assigned to receive chlorthalidone,
12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048);
or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately
4 to 8 years.
MAIN OUTCOME MEASURES: The primary outcome was combined fatal CHD or
nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary
outcomes were all-cause mortality, stroke, combined CHD (primary outcome,
coronary revascularization, or angina with hospitalization), and combined
CVD (combined CHD, stroke, treated angina without hospitalization, heart
failure [HF], and peripheral arterial disease).
RESULTS: Mean follow-up was 4.9 years. The primary outcome occurred
in 2956 participants, with no difference between treatments. Compared
with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were
0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99
(95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause
mortality did not differ between groups. Five-year systolic blood pressures
were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and
lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone,
and 5-year diastolic blood pressure was significantly lower with amlodipine
(0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary
outcomes were similar except for a higher 6-year rate of HF with amlodipine
(10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone,
lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%;
RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI,
1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31).
CONCLUSION: Thiazide-type diuretics are superior in preventing 1 or
more major forms of CVD and are less expensive. They should be preferred
for first-step antihypertensive therapy. |
