Download LEVAQUIN® (levofloxacin IV/tablets)

Hypertension and Dyslipidemia
An ominous—and common—combination
NED FERGUSON, M.D.
March 2004
NCEP ATP III
Metabolic Syndrome Criteria
Risk Factor*
Abdominal obesity† (waist circumference)
Men ‡
Women
TG
HDL-C
Men
Women
BP
FBG
Defining Level
>40 in
>35 in
>150 mg/dL
<40 mg/dL
<50 mg/dL
>130/>85 mmHg
110 mg/dL
*Diagnosis
is established when > 3 of these risk factors are present
obesity is more highly correlated with metabolic risk factors than is BMI
‡Some men develop metabolic risk factors when circumference is only marginally
increased
†Abdominal
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults. JAMA. 2001;285:2486-2497.
Key Challenges Overview: Summary

Obesity is significant risk factor for several
interrelated conditions
–
–
–
–



Hypertension
Dyslipidemia
Diabetes
Atherosclerosis
Even relatively low levels of elevated blood pressure
and lipids impart significant increased CVD risk
Hypertension and dyslipidemia often occur
concomitantly
Concomitant hypertension and dyslipidemia increase
CVD risk exponentially
Statement of Need
The scope:

Concomitant hypertension and dyslipidemia occurs more commonly
than would be expected in the general population

1 in 4 American adults have hypertension

~40% of US adults have total serum cholesterol levels > 200 mg/dL

Framingham data showed ~50% of men and women who presented
with treatable hypertension also had an abnormal lipid profile
The problem:

~27 million Americans have both hypertension and dyslipidemia

Only ~9 million have been diagnosed with both

Only ~3 million are being treated for both
The need:

When 1 condition is diagnosed, check for the other

If both are detected, treat maximally to decrease CVD risk and events
A Growing Need

More Americans than ever before could benefit from
treatment of hypertension and dyslipidemia
– The graying of the population
– More-aggressive guidelines JNC 7 and NCEP ATP III
– The weight of the evidence
– The evidence of the weight
national epidemic of obesity
JNC 7
More-Aggressive Guidelines
BP
Classification
Normal
Systolic BP,
mmHg*
Diastolic BP,
mmHg*
<120
And
<80
Prehypertension
120-139
Or
80-89
Stage 1 hypertension
140-159
Or
90-99
Stage 2 hypertension
>160
Or
>100
Goal of Therapy
Uncomplicated hypertension
Heart failure or target organ damage
Diabetes and/or chronic renal disease
Chronic renal disease with proteinuria
<140/90
<130/85
<130/80
<125/75
OVERCOMING CLINICAL INERTIA
TO CONTROL HYPERTENSION

Importance of systolic BP-explain seriousness
and urgency for treatment to patients

Need for multiple drugs is common-due to
progression of disease, not failure of care

“Mild” elevation of BP is not “mild”-patients will
suffer if this is not treated
ATP III
More-Aggressive Guidelines
Risk Category
CHD or CHD Risk
Equivalents
LDL Level at
LDL Level at Which
LDL Goal
(mg/dL)
Which to
to Consider
Initiate TLC (mg/dL)
Drug Therapy (mg/dL)
<100
>100
>130
(100-129: drug optional)
(10-year risk >20%)
2+ Risk Factors
<130
>130
(10-year risk <20%)
10-year risk 10%-20%: >130
10-year risk <10%: >160
>190
0-1 Risk Factor
<160
>160
(160-189: LDL-lowering
drug optional)
NCEP ATP III. JAMA. 2001;285:2486.
Six Stages of Medication Adherence

Stage 4: “You are ill. Take this medicine until you

Stage 5: “You are well. Take this medicine every
feel well, and continue for a lifetime of therapy,
even if you never again feel ill.”
day for the rest of your life to prevent illness.”
Courtesy: Ockene IS.
Six Stages of Medication Adherence

Stage 6: “You are well. Take this medicine, which
may make you feel sick, will be expensive, and will
constantly remind you that you have a ‘problem,’
every day for the rest of your life to prevent an
illness that is unlikely to occur for many years, and
that may never occur even if you don’t take the
medication.”
Courtesy: Ockene IS.
Adherence to Antihypertensive and
Lipid-Lowering Therapy Over Time

Only about 1 in 3 patients was classified as adherent to
concomitant antihypertensive and lipid-lowering therapy
over time.
– Another third was not adherent with either therapy in
each interval.
– Remainder of the population (25%-30%) was
adherent with one medication (usually
antihypertensive therapy) but not the other.

Adherence was better when therapies were initiated on
or about the same date (within 0-30 days of each other).
Chapman RH, et al. American Heart Association. 2003.
Nonadherence to Therapy:
A Major Challenge

Nonadherence (aka noncompliance, nonpersistance,
etc.) is a major problem

Within 1 year, ~50% of patients overall discontinue
use of drugs

An additional ~35% discontinue treatment within 2
years
National Council on Patient Information and Education, 1997.
Consequences of Nonadherence

Because of improper use, 30%-50% of prescriptions fail
to produce desired therapeutic results

Nonadherence causes unnecessary hospital admissions
costing $25 billion annually in the US
National Council on Patient Information and Education.
Berg JS, et al. Ann Pharmacother. 1993;27:S1-24.
Physician Adherence Management
Clinician uses problem-solving approach based on
questioning the patient in a nonjudgemental manner
 “How do you remember to take your medicine?”
 “As is the case with many patients, do you ever miss or
forget a dose?”
 “How do you remember to take your medication on
weekends or while traveling?”
 “What do you think you could do to avoid missing doses?”
 “Might any future events interfere with taking your
medication?”
Insull W. J Intern Med. 1997;241:317.
Concomitant Hypertension/Dyslipidemia:
Key Management Principles




Individualize care based on specific needs, but avoid unduly prioritizing
treatment of 1 condition over the other
Educate patients about CVD risk reduction
– Simultaneous blood pressure control and lipid-lowering through TLC
Employ treatment approaches that facilitate long-term adherence by
considering real-world issues
– Drug cost
– Dosing schedules
– Number of pills taken per day
– Adverse effects
Regularly update patients on current numbers and goals for both blood
pressure and lipids
– Explain significance of numbers
– Record goal in chart to prompt follow-up at each visit
JNC 7
Thorough Hypertension Evaluation

Physical examination
– Appropriate measurement of BP, verified in contralateral arm
– Optic fundi examination
– BMI calculation
– Auscultation for carotid, abdominal, femoral bruits
– Thorough examination of heart and lungs
– Examination of abdomen for enlarged kidneys, masses, abnormal
aortic pulsation
– Palpation of lower extremities for edema, pulses
– Neurological assessment
Chobanian AV, et al. JAMA. 2003;289:2560-2572.
JNC 7
Lifestyle Modifications



Healthy lifestyle is critical for hypertension management
– Reduces BP
– Enhances antihypertensive drug efficacy
– Decreases CVD risk
DASH diet (1600 mg sodium/d) may be as efficacious as
single-drug therapy
Combinations of > 2 modifications can achieve even
better results
Chobanian AV, et al. JAMA. 2003;289:2560-2572.
DASH Study
Effects of Diet on
Systolic and Diastolic Blood Pressure



Dietary Approaches to Stop Hypertension
459 adults with mild hypertension or high-normal blood
pressure (<160/80-95) randomized for 8 weeks to:
– Control diet or
– High fruit/vegetable diet or
– DASH combination diet (high fruit/vegetable, low
saturated fat and cholesterol, high calcium, high
potassium)
Sodium intake and body weight remained constant
Appel LJ, et al. N Engl J Med. 1997;336:1117-1124.
JNC 7
Combination Therapy



Most patients require > 2 drugs to achieve goals
If blood pressure > 20/10 mmHg above goal, consider initiating
treatment with 2 drugs
– Separate prescriptions, or fixed-dose combinations
– Using lower-than standard doses of > 2 drugs may improve
efficacy and reduce adverse effects
Use caution in patients at risk for orthostatic hypotension
– Diabetes
– Autonomic dysfunction
– Older patients
Chobanian AV, et al. JAMA. 2003;289:2560-2572.
Law MR, et al. BMJ. 2003;326:1427-1434.
How Low Should LDL-Cholesterol Be?
New Guidelines are Needed
BRITISH HEART PROTECTION STUDY: Simvastatin
40 mg reduces risk of CV events by 30% even in
patients with initial untreated LDL-C < 100 mg/dL
ARBITER: Regression of carotid atherosclerosis as
measured by carotid artery intima-media thickness
is directly related to the absolute LDL-C level
obtained on statin therapy. The greatest
regression occurred with an LDL-C < 70 mg/dL.
REVERSAL: The effect of 18 months of intensive
LDL-C lowering therapy with atorvastatin (46%
reduction from baseline) was compared with more
moderate therapy with pravastatin (25% from
baseline), in CHD patients.
The intensive LDL-C lowering regimen halted the
progression of atherosclerosis as measured by
total plaque volume using intravascular ultrasound
(IVUS).
ASCOT: In treated hypotensive patients, at
moderate risk for CV events and with average
baseline LDL-C of 130 mg/dL, 10 mg atorvastatin
reduced all CV events and stroke by 21-36%
compared with placebo. This effect emerged early
and led to early termination of the lipid-lowering
arm of the study. Final LDL-C on therapy was 84
mg/dL.
Events * in the Major Prevention Trials
Trial
4S
WOS
CARE
AFCAPS/
TexCAPS
LIPID
N
4444
6595
4159
6605
9014
# of
# of
% Events
Events Events
RR
Not
Placebo Statin Reduction Avoided
622
248
274
183
431
174
212
116
34
31
24
37†
66
69
76
63
715
557
24
76
Lancet 1994;344:1383-1389.
N Engl J Med. 1998;339:1329-1357.
*Nonfatal MI/CHD death
N Engl J Med. 1995;333:1301-1307.
JAMA. 1998;279:1615-1622.
†Includes unstable angina
N Engl J Med. 1996;335:1001-1009.
Low HDL
Cholesterol


Postprandial
Hyperlipidemia


Small,
Dense LDL


HYPERTRIGLYCERIDEMIA
Procoagulant State
Insulin Resistance
Triglyceride-Rich
Lipoprotein
Remnants
Figure 2. Association of elevated serum trigylceride levels and atherogenic risk
factors. Modified from Brewer HB Jr. Hypertriglyceridemia: changes in the
plasma lipoproteins associated with an increased risk of cardiovascular disease.
Am J Cardiol 1999;83:3F-12F, with permission from Excerpta Medica Inc.
Lowering LDL-C Is Not Enough
Despite significant lowering of LDL-C in the statin
trials, over 65% of treated patients continue to
have, or die from, CV events.
Most patients with atherosclerotic disease have a
mixed dyslipidemia with elevated LDL-C, but as
importantly, elevated triglycerides and low levels
of HDL-C.
This atherogenic lipid profile is characterized by small,
dense LDL lipoprotein particles and low levels of large,
protective HDL particles.
It appears that “ideal lipid goals” for high risk patients
need to be lower than published guidelines and prudent
and safe recommendations are:
TC
<150 mg/dL
TG
<100 mg/dL
HDL >50 mg/dL
LDL >70-80 mg/dL