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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 - PowerPoint PPT Presentation
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Double Trouble: HTN plus Dyslipidemia
Aggressive Management in Primary Care
Amelie Hollier, DNP, FNP-BC, FAANPAdvanced 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 diseaseStone 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 HEADLINESWho 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 75-150%
Ridker,P. Cook, N. (2013). Lancet, Opinion, Nov. 19, 2013.
Underestimates Risk???40 year old white male, non-smoker, no DM, systolic BP =120Father died of AMI 45 years oldTotal Cholesterol: 310 mg/dLHDL: 50 mg/dLLDL: 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, non-smoker, no DM, systolic BP =120Father died of AMI 45 years oldTotal Cholesterol: 310 mg/dLHDL: 50 mg/dLLDL: 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
Abandonment of the LDL Targets
• 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
Guidelines Controversy
(Goals: LDL < 100 mg/dL LDL < 70 mg/dL)
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” Groups1. Secondary prevention in adults < 75 years2. Primary prevention in adults with LDL > 190
mg/dL3. 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)
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.
Level C=consensus or expert opinion
Profit from 50% or > reduction in LDL with statin
Statins for “High Risk” Groups
Recommendation: Need LDL reduction of 50% or greater, use:
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 Dosage in mg GenericAtorvastatin 40* , 80 YesRosuvastatin 20, 40 No
* 40 mg if 80 mg not tolerated
Statin CYP 450 EffectAtorvastatin Rosuvastatin
LDL Decrease 50-60%40-80mg
50-63%20-40 mg
CYP 450 Effect 3A4 enzymes Not significantly metabolized by CYP 450
“Moderate Risk” Groups1. Secondary prevention in adults > 75 years
old2. 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)
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.
Level A=High quality RCT, high quality meta-analysis
Profit from 30-49% reduction in LDL with statin
“Moderate Risk” GroupsProfit from 30-49% reduction in LDL with statin
Circulation. 2013 Nov.
Statin Dosage in mg GenericAtorvastatin 10, 20 YesFluvastatin 40 BID; 80 daily YesLovastatin 40 Yes
Pitavastatin 2, 4 NoPravastatin 40, 80 Yes
Rosuvastatin 5, 10 NoSimvastatin 20, 40 Yes
CYP 450 EffectAtorvastatin Simvastatin Lovastatin
LDL Decrease
35-43%10-20mg
29-41%10-40 mg
24-42%20-80 mg
CYP 450 Effect
3A4 Strong 3A4 3A4
Pitavastatin Pravastatin Rosuvastatin
LDL Decrease
36-45%2-4 mg
29-37%20-80 mg
45-49%5-10 mg
CYP 450 Effect
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.
Statins2012: Removal of routine monitoring of liver enzymes from statin drug labels
Statins• FDA conducted 5 previous post-
market 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 DiabetesStatins associated with
increased risk of NOD (new onset DM) in patients with 2-4 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”
EzetimibeCholesterol absorption inhibitors
• Can be combined with a statin• ENHANCE trial: Reductions in LDL
and increases in HDL, BUT……..
EzetimibeENHANCE Trial• Simvastatin plus ezetimibe vs.
simvastatin• No change in primary outcome (carotid
intima-media thickness)
HypertriglyceridemiaWhen 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!
HypertriglyceridemiaManagement• 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
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.
E-published in Dec, 2013
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
140/90 150/90< 60 years old > 60 years
DMCKD
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.
Start Pharmacotherapy* if BP exceeds:
*Continue lifestyle changes
JNC 8: Patients with Diabetes
• < 140/90 mmHg• Evidence Level A (high quality RCTs)• Unproven clinical benefit to lower
BPs more than 140/90Curb 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
140/90 150/90*< 80 years old > 80 years
> 80 years and CKD or DM
Start Pharmacotherapy if BP exceeds:
*Level ABeckett 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
Goal is at provider discretion; lower goal can be considered
What Med?
JNC 8: Initial ChoiceAfrican AmericanWith or without DM
Non-BlackWith or without DM
Thiazide diuretic 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. 6-12 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 DiureticsHCTZ, 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!
• Consider chlorthalidone or indapamide
• More evidence for improving cardiovascular outcomes than HCTZ
Need a thiazide?
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
ACE plus CCB better than
ACE plus thiazide
Even though both had good BP controlGuess which thiazide?
Trial stopped early
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 ChoiceAfrican AmericanWith or without DM
Non-BlackWith or without DM
Thiazide diuretic 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 HTNGeneral 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 HTNRenovascular 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 HTNCause Clues
Primary Aldosteronism Hypokalemia, urinary potassium wasting
Sleep apnea Syndrome Daytime sleepiness, loud snoring
Hypothyroidism Elevated TSH
Primary Hyperparathyroidism Elevated serum calcium
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
• J Hypertens. 2011;29(4):623.Syncope and renal impairment likely
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 AssociatesLafayette, LA