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Black Male With Hypertension and Average Cholesterol Concentrations
Putting Trial Results Into Practice
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Keith C. Ferdinand, MD |
The following case was provided by NLEC Faculty Member
Keith C. Ferdinand, MD, Professor of Clinical Pharmacology,
Xavier University College of Pharmacy, and Medical Director,
Heartbeats Life Center, New Orleans, Louisiana.
Disclosure Information for Dr Ferdinand: Research support:
Pfizer Inc; Novartis; Merck & Co., Inc.; AstraZeneca
JB is a 58-year-old black male presently working as a transit
operator. He smokes a half to one pack of cigarettes daily.
He has had high blood pressure (BP) for more than 15 years
but would rather not take medication for it. JB is also aware
of his elevated cholesterol, which was noted at a recent health
fair. He is seeking advice on the need for therapy for his
BP and/or dyslipidemia.
Background
In the United States alone, 50 million people have hypertension
and 105 million have high cholesterol—roughly 50%
of the population.1 Many
of these individuals have both conditions simultaneously.
This combination presents a treatment challenge, as these
patients may not appear to be at high risk based on BP or
lipids alone.
Drawing on data from the recent Antihypertensive
and Lipid-Lowering Treatment to Prevent Heart Attack Trial
(ALLHAT), the physician starts JB on hydrochlorothiazide
(HCTZ) 25 mg. However, after several weeks, his BP remained
between 152/98 mm Hg and 162/99 mm Hg (Stage 1 and Stage
2 hypertension, respectively, according to the recently
released Seventh Report of the Joint National Committee
on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure, or JNC 72).
(See Table 1.)
| Table 1. JNC 7:
Management of Blood Pressure for Adults* |
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Discussion
of Recent Clinical Trials
BP Reduction. Additional medication could
include a wide range of selections. According to ALLHAT,3
a long-acting dihydropyridine calcium channel blocker (amlodipine)
may effectively lower blood pressure in high-risk patients,
including blacks. The relative risks of combined primary
end points—fatal coronary heart disease (CHD) and
nonfatal MI—seen with amlodipine were comparable to
results seen with the diuretic chlorthalidone. Furthermore,
compared with chlorthalidone, amlodipine produced similar
reductions in secondary cardiovascular end points, including
stroke, combined CHD, combined cardiovascular disease (CVD),
and total mortality.
Although ALLHAT did not study the
combination of calcium channel blockers (CCB) and diuretics,
CCBs appear to be effective as alternative agents, especially
in black patients, who comprised 36% of the ALLHAT cohort.
CCBs may also equally protect against progression to end-stage
renal disease (ESRD), although the period studied in ALLHAT
was relatively short (range of 3–8 years).3
By adding an angiotensin receptor
blocker (ARB) or angiotensin-converting enzyme (ACE) inhibitor
to a diuretic, additional BP lowering with the benefit of
blocking the renin angiotensin system could be expected.
In fact, the lack of a diuretic in the lisinopril arm of
ALLHAT may have been a factor in the 4-mm higher systolic
BP and a subsequent 40% increase in the risk of stroke in
the black cohort, versus a chlorthalidone-based regimen
in blacks.3
In the Losartan Intervention For
Endpoint reduction in hypertension (LIFE) study, black patients
treated with the ß-blocker atenolol were at lower
risk of experiencing the primary composite end point than
were black patients treated with the ARB losartan.4,5
The cohort of black patients in the LIFE study was small
(533; 6% of total study patient population). Given the difficulty
in interpreting subset differences in large trials, it cannot
be known whether the observed difference is the result of
chance. However, the LIFE study provides no evidence of
reduction in CVD and stroke in blacks with losartan versus
atenolol.
Lipid Lowering.
No significant benefits in terms of all-cause mortality
or coronary and stroke events were apparent with pravastatin
40 mg/d compared with usual care in ALLHAT’s Lipid-Lowering
Trial (LLT).6 Adherence
to assigned treatment declined over time, perhaps diminishing
outcome differences between the pravastatin cohort and the
usual-care group; adherence to pravastatin dropped from
87% at year 2 to 80% at year 4. Furthermore, in the usual-care
group, crossover to any statin was 17% by year 4.6
The recently released lipid-lowering
arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA),
on the other hand, confirmed the benefit of lipid lowering
with atorvastatin 10 mg in patients with relatively modest
LDL-C levels who are also hypertensive (P=0.0005).
A 36% reduction in fatal CHD and nonfatal MI compared with
placebo was noted.7
The black patients in ALLHAT-LLT appeared
to have benefitted somewhat more than the trial’s general
population.6 (ASCOT did not
include black patients as an individual study group [see
Table 2].) In the pravastatin versus usual-care groups,
the relative risk for CHD death plus nonfatal MI was significantly
lower in blacks than in nonblacks (0.73; 0.58–0.92).
However, it was higher for strokes, with no overall difference
for combined cardiovascular events.6
| Table 2. Ethnicity
Demographics in Two Trials |
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ALLHAT-LLT does not support the
hypothesis that treatment with pravastatin reduces CHD risk
and mortality independent of cholesterol lowering. Nevertheless,
LDL-C reduction remains an important goal of therapy in
high-risk patients, including those with hypertension. Thus,
potency of LDL-C reduction versus any postulated pleiotropic
effects of certain statins appears to be most important
for risk reduction.
Treatment
Regimen
JB was initially treated with lifestyle modification, including
counseling on smoking cessation and the low-sodium DASH
(Dietary Approaches to Stop Hypertension) diet.8
Six months later, the patient is on a combination of HCTZ
25 mg, amlodipine 5 mg, and ramipril 10 mg. He has stopped smoking and has
gained 1 lb. His BP is now 132/84 mm Hg, which qualifies
him as “prehypertensive,” according to JNC 7.2
(See Table 1.) Based on the results of ASCOT, atorvastatin
10 mg was added to JB’s regimen. Three months later, his lipid levels are TC 163
mg/dL; LDL-C 90 mg/dL; TG 114 mg/dL; HDL-C 50 mg/dL.
Lessons
Learned
High blood pressure is an important CVD risk factor; thus,
lowering BP decreases that risk. Based on 12.7 million person-years
in the recent Prospective Studies Collaboration (a meta-analysis
of 61 observational studies),9
CVD risk begins at 115 mm Hg systolic and 75 mm Hg diastolic.
Thiazide-type diuretics remain the first step to BP control.
However, especially in black patients, CCBs remain useful
alternatives. ACE inhibitors and ARBs may offer benefit, but
in black patients they should be added to a diuretic for maximum
effect. Most patients who are hypertensive will require two
or more antihypertensive medications to achieve their BP goals.2
When BP is more than 20/10 mm Hg above goal, clinicians should
consider initiating a two-drug regimen. Drug therapy with
more than one agent may increase the likelihood of reaching
BP goal faster than with monotherapy.2
| Figure. Total
Cholesterol Distribution: CHD vs Non-CHD Population |
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Because it’s been shown that
50% of CHD occurs in individuals with below-average TC,
it is believed that findings from ASCOT-LLA will be widely
applicable to a large portion of the US population. (See
Figure.) The findings show that, in hypertensive patients
with average cholesterol levels who were at moderate risk
of developing cardiovascular events, cholesterol lowering
with atorvastatin 10 mg conferred a 36% reduction in fatal
CHD and nonfatal MI compared with placebo.7
This lipid-lowering arm of ASCOT included 10,305 people
with nonfasting TC concentrations of <251 mg/dL
plus three or more additional CVD risk factors. They had
baseline averages of 213 mg/dL TC and 131 mg/dL LDL-C.7
(Our case patient, JB, is very similar to the ASCOT-LLA
population.) Based on ASCOT-LLA, aggressive lipid-lowering
therapy with atorvastatin may demonstrate major cardiovascular
event reduction in combined hypertensive–dyslipidemic
patients over a short period of time.7
Conclusion
Persons with high serum cholesterol have a higher-than-expected
prevalence of hypertension, and persons with hypertension
have a higher-than-expected prevalence of high serum cholesterol.
According to the National Cholesterol Education Program
(NCEP), the second National Health and Nutrition Examination
Survey (NHANES II) showed that 40% of the ~50 million individuals
with hypertension (considered at the time >140/90
mm Hg or on antihypertensive medications) have cholesterol
levels >240 mg/dL, and 46% of those with cholesterol
levels >240 mg/dL have elevated BP.10
The risk gradient for systolic and diastolic BP is similar
to that for serum cholesterol: the higher the BP, the greater
the risk for CHD. In persons with both elevated cholesterol
and high blood pressure, CHD risk is synergistically increased.
Conversely, reducing BP, like cholesterol lowering, decreases
the risk for CVD.
According to JNC 7, diet and other
lifestyle changes are essential first-step therapies for
elevated BP and cholesterol.2
Diuretics may slightly raise LDL-C levels and some ß-blockers
may depress HDL-C levels, but these drugs should not be
avoided if their nonuse means less-than-optimal BP control.
Several antihypertensive agents
affect lipid levels; others do not. For example, nondihydropyridines,
CCBs, ACE inhibitors, ARBs, direct vasodilators, potassium-sparing
diuretics, and some centrally acting drugs have minimal,
if any, effects on serum lipids.2
Higher doses of thiazide diuretics can cause modest and
often transient elevations (5–10 mg/dL) in serum TC
, LDL-C, and TG with little or no adverse effect on HDL-C.11
References*
| 1. |
AHA. Heart Disease
and Stroke Statistics—2003 Update. AHA. 2002. |
| 2. |
National High Blood Pressure
Education Program Coordinating Committee. JAMA. 2003;289:2560-2572. |
| 3. |
ALLHAT Collaborative Research
Group. JAMA. 2002;288:2981-2997. |
| 4. |
Dahlöf B et al. Lancet.
2002;359:995-1003. |
| 5. |
Losartan [package insert].
Merck & Co., Inc. March 2003. |
| 6. |
ALLHAT Collaborative Research
Group. JAMA. 2002;288:2998-3007. |
| 7. |
ASCOT Investigators. Lancet.
2003;361:1149-1158. |
| 8. |
HHS. The DASH Diet.
NHLBI, NIH. NIH Publication No. 01-4082. |
| 9. |
Prospective Studies Collaboration.
Lancet. 2002;360: 1903-1913. |
| 10. |
HHS. NHANES II.
CDC, National Center for Health Statistics. |
| 11. |
Grundy S et al. Circulation. 2002;106:3143. |
*For
complete citations, please click here.
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