Double Trouble:
HTN plus Dyslipidemia
Aggressive Management in
Primary Care
Amelie Hollier, DNP, FNP-BC, FAANP
Advanced Practice Education Associates
Fatty Streak
• Intracellular lipids and extracellular deposits
make up the fatty streak
• Macrophages are part of the inflammatory
process
• They absorb lipids and are called foam cells
• Foam cells are the hallmark of early
atheroma
• Just expands!
How can we
slow down or
stop this
process?
Manage Risk Factors
• Dyslipidemia
• Hypertension
• Smoking
• Diabetes (a disease of endothelial
dysfunction)
• Elevated serum CRP
The ACC/AHA 2013 HEADLINES
Who Benefits from a Statin?
• History of CHD or stroke (secondary
prevention of ASCVD)
• Patients with LDL >190 mg/dL
ASCVD=atherosclerotic cardiovascular disease
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic
Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines. Circulation 2013.
The ACC/AHA 2013 HEADLINES
Who Benefits from a Statin?
• DM (no evidence of ASCVD), 40-75 years old
with LDL 70-189 mg/dL
• Patients (without evidence of ASCVD or DM)
with LDL 70-189 mg/dL PLUS estimated 10
year risk of ASCVD > 7.5%
Circulation. 2013 NovStone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood
Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines. Circulation 2013.
Pooled Cohort Equations
CV Risk Calculator
• Framingham Risk Score (FRS) had always
been the standard
• http://my.americanheart.org/cvriskcalculator
(spreadsheet)
• Many available for free download for Apple
and for Android products
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines. Circulation 2013.
Pooled Cohort Equations
CV Risk Calculator
• Big CRITICISM of risk calculator is that it
OVERESTIMATES patient risks (compared to
Framingham)
Ridker,P. Cook, N. (2013). Lancet, Opinion, Nov. 19, 2013.
Pooled Cohort Equations
CV Risk Calculator
• 2 MDs calculated the 10 year risk of CV
events using the new risk calculator in
Women’s Health Study (WHS), Physicians
Health Study (PHS), and Women’s Health
Initiative Observational Study (WHI-OS)
• New risk calculator overestimated risk by 75150%
Ridker,P. Cook, N. (2013). Lancet, Opinion, Nov. 19, 2013.
Underestimates Risk???
40 year old white male, non-smoker, no DM,
systolic BP =120
Father died of AMI 45 years old
Total Cholesterol: 310 mg/dL
HDL: 50 mg/dL
LDL: 180 mg/dL
Calculated 10 yr risk = 2.4%
What if your patient
doesn’t fit into one of these
4 groups?
40 year old white male, nonsmoker, no DM, systolic BP =120
Father died of AMI 45 years old
Total Cholesterol: 310 mg/dL
HDL: 50 mg/dL
LDL: 180 mg/dL
Calculated 10 yr risk = 2.4%
What if your patient doesn’t fit
into this group?
“Additional factors can be taken into
consideration”
•
•
•
•
•
•
•
LDL > 160 mg/dL or genetic hyperlipidemia
ASCVD in male FDR prior to age 55 years
ASCVD in female FDR prior to 65 years
hsCRP > 2 mg/dL
ABI < 0.9
Elevated lifetime risk of ASCVD
Elevated calcium score
Guidelines Controversy
Abandonment of the LDL Targets
(Goals: LDL < 100 mg/dL LDL < 70 mg/dL)
• Randomized, controlled clinical
trials demonstrated benefit using
specific statin doses---NOT achieving
LDL targets
• Recommendation: Continue to
measure LDL levels but don’t target
specific numbers
What Drug Class to
Reduce Risks?
• Statins are FIRST choice!
• Statins are ONLY class to
demonstrate reductions in mortality
in primary and secondary
prevention
• Non-statins?
“High Risk” Groups
Profit from 50% or > reduction in LDL with statin
1. Secondary prevention in adults < 75 years
2. Primary prevention in adults with LDL > 190
mg/dL
3. Primary prevention in adults 40-75 years
with LDL 70-189 mg/dL PLUS estimated
ASCVS risk of > 7.5%
4. Primary prevention in DM 40-75 years of age
with LDL 70-189 mg/dL PLUS estimated
ASCVD risk of > 7.5% (Level C) Level C=consensus or expert opinion
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines. Circulation 2013.
Statins for
“High Risk” Groups
Recommendation: Need LDL reduction of 50%
or greater, use:
Statin
Atorvastatin
Rosuvastatin
Dosage in mg
40* , 80
20, 40
Generic
Yes
No
* 40 mg if 80 mg not tolerated
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines. Circulation 2013.
Statin CYP 450 Effect
LDL Decrease
Atorvastatin
Rosuvastatin
50-60%
40-80mg
50-63%
20-40 mg
CYP 450 Effect 3A4 enzymes
Not
significantly
metabolized
by CYP 450
“Moderate Risk” Groups
Profit from 30-49% reduction in LDL with statin
1. Secondary prevention in adults > 75 years
old
2. Primary prevention in adults 40-75 years
with LDL 70-189 mg/dL PLUS estimated
ASCVS risk of > 7.5% (could use high dose)
3. Primary prevention in DM 40-75 years of age
with LDL 70-189 mg/dL PLUS estimated
ASCVD risk of > 7.5% (Level A)
Level A=High quality RCT, high quality meta-analysis
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines. Circulation 2013.
“Moderate Risk” Groups
Profit from 30-49% reduction in LDL with statin
Statin
Atorvastatin
Fluvastatin
Lovastatin
Pitavastatin
Pravastatin
Rosuvastatin
Simvastatin
Circulation. 2013 Nov.
Dosage in mg
10, 20
40 BID; 80 daily
40
2, 4
40, 80
5, 10
20, 40
Generic
Yes
Yes
Yes
No
Yes
No
Yes
CYP 450 Effect
Atorvastatin
LDL
Decrease
CYP 450
Effect
35-43%
10-20mg
3A4
Pitavastatin
LDL
Decrease
CYP 450
Effect
Simvastatin
29-41%
10-40 mg
Strong 3A4
Pravastatin
Lovastatin
24-42%
20-80 mg
3A4
Rosuvastatin
36-45%
2-4 mg
29-37%
20-80 mg
45-49%
5-10 mg
Not significantly
metabolized by
CYP 450
Not significantly
metabolized by
CYP 450
Not significantly
metabolized by
CYP 450
If a patient is intolerant of a
moderate or high dose of a statin,
OK to use a low dose statin.
Take Home Point:
Get the patient on a
statin!
Monitoring Statin
Therapy
Recommendation: Ask about any
pre-existing muscle symptoms
PRIOR to starting statin
Circulation. 2013 Nov.
Statin Tolerability
• Myopathic syndromes: myalgias =>
rhabdo
• Myalgias can occur WITHOUT
elevations is serum creatinine kinase
• Rhabdo UNCOMMON! (<0.1%)
• Frequency of myalgias: 2-11%
• Begin weeks to months after starting
statins
• Least problematic: pravastatin,
fluvastatin, rosuvastatin
Possible Etiologies
• Inhibition of Coenzyme Q10
production
• Decreased cholesterol content in
muscle cell membranes
Coenzyme Q-10
•
•
•
•
•
Made by humans every day
Cofactor in several metabolic pathways
Ingested in fish, meats, soybean oil
Anti-oxidant
Stains impair your ability to make
Coenzyme Q-10
Myalgias: Other thoughts
• Consider rosuvastatin or
atorvastatin M-W-F or Tues or Thurs
• Check lipids on M-W-F if statin 3
times weekly
• Don’t forget to check Vitamin D
levels (this can cause muscle pain)
Monitoring Statin Therapy
• Check ALT (alanine aminotransferase) at
baseline. Repeat only if symptoms of
hepatotoxicity occur.
Circulation. 2013 Nov.
Statins
2012: Removal of routine
monitoring of liver enzymes from
statin drug labels
Statins
• FDA conducted 5 previous postmarket reviews between 2000 and
2009
• Finding: Statin-associated serious
liver injury was extremely low
• “we conclude that statin-associated
severe liver injury is an extremely
rare event and appears to be largely
idiosyncratic”
Statins
• FDA Recommendation: “perform
liver enzyme tests before the
initiation of statin therapy (as a
baseline) and as clinically indicated
thereafter”
• Stop statin if ALT 3 times
upper
limits of normal
Monitoring Statin Therapy
• Recheck lipid panel 4-12 weeks after
statin initiated, then every 3-12
months
• If LDL < 40 mg/dL on 2 consecutive
measurements, reduce statin dose
Circulation. 2013 Nov.
Monitoring Statin Therapy
• “Monitor for new-onset diabetes”
Circulation. 2013 Nov.
Another Label Change
Feb. 2012
• FDA issued new labeling
changes for the entire
statin drug class
• All must carry a warning
about reports of increased
blood sugar and A1c with
statin use
Pravastatin
• WOSCOPS: West of Scotland Coronary
Prevention Study
• 30% decrease in the incidence of DM in
patients taking pravastatin
Type 2 Diabetes
Statins associated with
increased risk of NOD (new
onset DM) in patients with 24 risk factors for DM
No increased risk of NOD in
patients with low risk of DM
Journal of American College of Cardiology, Jan. 2013
What if you can’t reach %
reduction with statin?
• Reinforce lifestyle changes
• Look for a secondary cause
What if you can’t reach
% reduction with statin?
Non-Statins???
“Don’t routinely use non-statins”
Ezetimibe
Cholesterol absorption inhibitors
• Can be combined with a statin
• ENHANCE trial: Reductions in LDL
and increases in HDL, BUT……..
Ezetimibe
ENHANCE Trial
• Simvastatin plus ezetimibe vs.
simvastatin
• No change in primary outcome (carotid
intima-media thickness)
Hypertriglyceridemia
When Trigs > 500 mg/dL
• Goal is to prevent pancreatitis
by lowering trigs
• Once trigs < 500 mg/dL, address
LDL goal! Use a statin!
• Reduction of cardiovascular risks!
Hypertriglyceridemia
Management
• Trigs 150-199 mg/dL: Weight reduction,
increased physical activity
• Trigs 200-499 mg/dL: Attack LDL first, then
trigs
• Trigs >500 mg/dL: prevent pancreatitis first
with non-pharm plus meds. When below 500
mg/dL, address LDL!
Hypertension Management
Critical in preventing ASCVD!
Unless you’ve been in a cave…
2014 Evidence Based Guideline for
management of high blood
pressure in adults: report from
panel members appointed to the
Eight Joint National Committee
E-published in Dec, 2013
James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the
management of high blood pressure in adults: report from the panel
members appointed to the Eighth Joint National Committee (JNC 8). JAMA
2014; 311:507.
JNC 8 Guidelines
• Controversial!
• ACC/AHA released a
statement: Anticipate new
guideline in 2015
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol
to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.
2013: American Society of
Hypertension and International
Society of Hypertension
Wasn’t controversial!
Expert Opinion ASH/ISH
Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in
the community: a statement by the American Society of Hypertension and the International Society of
Hypertension. J Clin Hypertens (Greenwich) 2013 Dec 17. doi: 10.1111/jch.12237. [Epub ahead of print].
JNC 8 Guidelines
• Evidence Based (different from JNC
7)
• Lead author, Dr. Paul James, “we
wanted to make the message very
simple”
• 14 pages (vs. 51 pages for the lipids)
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol
to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.
“Consensus”
Lifestyle Changes (evidence based)
• Healthy Eating Habits
(Mediterranean diet?)
• Limit Na intake to 2400 mg daily
• Stop smoking
• Achieve healthy weight
• Regular physical activity
JNC 8: BP by Age
Start Pharmacotherapy* if BP exceeds:
140/90
150/90
< 60 years old
DM
CKD
> 60 years
*Continue lifestyle changes
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol
to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013.
JNC 8: Patients with Diabetes
• < 140/90 mmHg
• Evidence Level A (high quality RCTs)
• Unproven clinical benefit to lower
BPs more than 140/90
Curb JD, Pressel SL, Cutler JA, et al. Effect of diuretic-based antihypertensive treatment on
cardiovascular disease risk in older diabetic patients with isolated systolic hypertension.
Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA
1996;276:1886-92.
Tuomilehto J, Rastenyte D, Birkenhager WH, et al. Effects of calcium-channel blockade in older
patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial
Investigators. N Engl J Med 1999;340:677-84.
UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular
and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13.
ACCORD Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood pressure
control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85.
American Diabetes Association
• BP Goal < 140/80 mmHg
• ACCORD: Intensive BP lowering did
not result in reduced risk of fatal or
non-fatal CV events in adults with
Type 2 DM who were at high risk of
these events (and they had more side
effects related to intensive treatment)
ACCORD Study Group, Cushman WC, Evans GW, et al. Effects of intensive
blood pressure control in type 2 diabetes mellitus. N Engl J Med
2010;362:1575-85.
JNC 8: Patients > Age 60 years
• BP target < 150/90 mmHg
• Evidence Level B (low quality RCTs)
• If tolerating lower BP, then OK
JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood
pressure in elderly hypertensive patients (JATOS). Hypertens Res 2008;31:2115-27.
Oglihara T, Saruta T, Rakugi H, et al. Target blood pressure for treatment of isolated systolic
hypertension in the elderly: valsartan in elderly Isolated systolic hypertension study.
Hypertension 2010;56:196-202.
ASH: BP by Age
Start Pharmacotherapy if BP exceeds:
140/90
150/90*
< 80 years old
> 80 years and CKD
or DM
> 80 years
Goal is at provider discretion; lower goal can be considered
*Level A
Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of
age or older. N Engl J Med 2008;358:1887–98
What Med?
JNC 8: Initial Choice
African American
Non-Black
With or without DM
Thiazide diuretic
With or without DM
Thiazide diuretic
Calcium channel
blocker
Calcium channel
blocker
ACE
ARB
JNC 8
Take Home Point
• Diabetics no longer treated as
different from general
population (at least initially)
• No deference to ACEs or ARBs
No ACEs or ARBs for DMs
initially
• Patients with DM are at increased
risk of CV events and nephropathy--ACEs and ARBs are beneficial
• ASH: makes sense to use these first line
in patients with diabetes
JNC 8
Take Home Point
• Thiazides no longer “only” first
line agent to treat HTN unless
“compelling indications”
Hydrochlorothiazide
Most commonly prescribed
diuretic for HTN in the world!
•
• Starts working in about 2
hours
• Half life 6-12 hours
• Sulfa allergy precaution!!!
Chlorthalidone
• Most evidence for improved CV
outcomes
• Twice as potent as HCTZ
• Appears to work in the ascending
limb of Henle’s loop (2.6 h initial diuresis occurs)
• Longer half-life (up to 72 hours vs. 612 with HCTZ)
• Longer control of BP!!!
Indapamide
• Half life is about 14 hours
• Indications: HTN, salt and fluid
retention associated with HF
• Disadvantage: Not found in
combo with other BP meds
• Cheap! ($4 drug)
Indapamide (Lozol)
• 1.25 mg daily; if not at BP goal
after 4 weeks, increase to 2.5 mg
daily
• 2.5, 5, 10 mg tabs demonstrated
equal efficacy
Consider a different agent if goal BP
not achieved by 8 weeks
Thiazide Diuretics
HCTZ, indapamide, chlorthalidone
• Systolic reduction: 5-16.4 mmHg
• Diastolic reduction: 2-9.3 mmHg
• Minimal decreases in potassium (check
potassium levels after 2 weeks of
therapy).
• Keep K at least 4 mm/L
• Reduces LVH (equivalent to ACEs?)
Take Home Point!
Need a thiazide?
• Consider chlorthalidone or
indapamide
• More evidence for improving
cardiovascular outcomes than HCTZ
Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management
of hypertension in the community: a statement by the American Society of Hypertension
and the International Society of Hypertension. J Clin Hypertens (Greenwich) 2013 Dec 17.
doi: 10.1111/jch.12237.
JNC 8
Take Home Point
• Thiazides no longer “only” first
line agent to treat HTN unless
“compelling indications”
HTN in African Americans
• HTN is a MAJOR issue in AA
• Earlier onset than in other ethnic
groups
• Usually of greater severity
• HTN is associated with CV and renal
complications
Take Home Point!
CCBs provide better
stroke prevention than
ACE or ARB in AA.
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of
Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of
the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines. Circulation 2013.
Take Home Point!
When giving an ACE or ARB
to an AA, add thiazide
diuretic!
(or ACE or ARB plus CCB)
Erase cultural differences!
Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management
of hypertension in the community: a statement by the American Society of Hypertension
and the International Society of Hypertension. J Clin Hypertens (Greenwich) 2013 Dec 17.
doi: 10.1111/jch.12237.
ACCOMPLISH Trial
Trial stopped early
ACE plus CCB
better than
ACE plus thiazide
Guess which thiazide? 
Even though both had good BP control
N Engl J Med 2008;359:2417-28.
ACCOMPLISH Trial
ACE plus CCB
WHY???
Prevented more CV events (one for
every 135 high risk patients treated
for one year)
N Engl J Med 2008;359:2417-28.
What drug classes
are missing from
initial treatment?
JNC 8: Initial Choice
African American
Non-Black
With or without DM
Thiazide diuretic
With or without DM
Thiazide diuretic
Calcium channel
blocker
Calcium channel
blocker
ACE
ARB
Alpha and Beta
Blockers
Associated with worse
cardiovascular outcomes
data (HTN treatment)
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of
Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of
the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines. Circulation 2013.
JNC 8: Chronic Kidney Disease
African American
Non-Black
ACE
ACE
ARB
ARB
ACE or ARB even in African American
JNC 8 “FYI”
Wait 2-3 weeks before
increasing medication or
adding a new medication
JNC 8 “FYI”
Can initiate treatment with two
agents if systolic > 20 mmHg
above goal; or diastolic > 10
mmHg above goal
JNC 8 “FYI”
If more than 3 drug classes are
needed to control BP, consider
referral.
3 or more Agents???
•
•
•
•
Thiazide diuretic
ACE or ARB
CCB
Alpha blocker (have another
reason to give it-BPH)
• Beta Blocker (have another
reason to give it-anxiety,
angina, rate control, MVP, HF)
3 or more Agents???
FYI
• ACE or ARB is always less
effective when given in combo
with a Beta blocker
• BB reduce renin secretion and
therefore, AT2 formation
3 or more Agents???
• Consider referral to HTN specialist
if intensive treatment for 6 months
doesn’t bring about normotensive
state
• Always suspect secondary
hypertension
Secondary HTN
General Clues
Severe or Resistant Hypertension
An acute rise after previously stable
Age of onset at or before puberty
HTN < 30 years without risk factors
Secondary HTN
Renovascular Cause
Acute elevation (30% or >) in creatinine after
initiation of ACE or ARB
Severe HTN plus asymmetric kidney or renal size
disparity of 1.5 cm between kidneys
Onset of BP > 160/100 after age 55 years
Secondary HTN
Cause
Clues
Primary Aldosteronism
Hypothyroidism
Hypokalemia, urinary
potassium wasting
Daytime sleepiness,
loud snoring
Elevated TSH
Primary
Hyperparathyroidism
Elevated serum calcium
Sleep apnea Syndrome
JNC 8 “FYI”
Do not add an ACE plus ARB to
a medication regimen; either
one or the other—NOT BOTH.
ACE + ARB???
• ONTARGET trial: ramipril plus
telmisartan in 25,000 patients at
high risk for CV events (DM or
vascular disease)
• Predictable outcomes:
hypotension, syncope,
hyperkalemia, renal dysfunction
ACE + ARB???
Does not improve CV outcomes in:
• Patients with DM
• Patients with vascular disease
• Patients with HTN
• Patients Post-MI
•
Syncope and renal impairment likely
J Hypertens. 2011;29(4):623.
Continuously evaluate patient risk
factors and be aggressive in
management!
Statin Drug Class
• Statins are FIRST choice!
• Statins are ONLY class to
demonstrate reductions in mortality
in primary and secondary
prevention
Use evidence based
guidance to determine
BP goal for your patient!
To reduce morbidity and
mortality associated with
ASCVD…..
Manage risk factors!
Manage risk factors!
Manage risk factors!
Thank you!
To Reach me:
Amelie Hollier, DNP, FNP-BC, FAANP
Advanced Practice Education Associates
Lafayette, LA
amelie@apea.com