Double Trouble: HTN plus Dyslipidemia Aggressive Management in Primary Care

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.


• Big CRITICISM of risk calculator is that it OVERESTIMATES patient risks (compared to Framingham)

Ridker,P. Cook, N. (2013). Lancet, Opinion, Nov. 19, 2013.


• 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)


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:


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


CYP 450


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


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.


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


Monitoring Statin Therapy• “Monitor for new-onset diabetes”


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


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


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


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


• 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.


• 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.


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



ACE

ARB

Alpha and Beta Blockers

Associated with worse cardiovascular outcomes data (HTN treatment)


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

[email protected]

Double Trouble: HTN plus Dyslipidemia Aggressive Management in Primary Care

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