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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

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double trouble htn plus dyslipidemia aggressive management in primary care

Double Trouble: HTN plus DyslipidemiaAggressive Management in Primary Care

Amelie Hollier, DNP, FNP-BC, FAANP

Advanced Practice Education Associates

fatty streak
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!
manage risk factors
Manage Risk Factors
  • Dyslipidemia
  • Hypertension
  • Smoking
  • Diabetes (a disease of endothelial dysfunction)
  • Elevated serum CRP
the acc aha 2013 headlines
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 headlines1
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/dLPLUS 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
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 calculator1
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 calculator2
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
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
What if your patient doesn’t fit into one of these 4 groups?

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 this group
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

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 r isks
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
“High Risk” Groups

Profit from 50% or > reduction in LDL with statin

  • Secondary prevention in adults < 75 years
  • Primary prevention in adults with LDL > 190 mg/dL
  • Primary prevention in adults 40-75 years with LDL 70-189 mg/dL PLUS estimated ASCVS risk of > 7.5%
  • 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
Statins for “High Risk” Groups

Recommendation: Need LDL reduction of 50% or greater, use:

* 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.

moderate risk groups
“Moderate Risk” Groups

Profit from 30-49% reduction in LDL with statin

  • Secondary prevention in adults > 75 years old
  • Primary prevention in adults 40-75 years with LDL 70-189 mg/dLPLUS estimated ASCVS risk of > 7.5% (could use high dose)
  • Primary prevention in DM 40-75 years of age with LDL 70-189 mg/dLPLUS 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 groups1
“Moderate Risk” Groups

Profit from 30-49% reduction in LDL with statin

Circulation. 2013 Nov.

if a patient is intolerant of a moderate or high dose of a statin
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
Monitoring Statin Therapy

Recommendation: Ask about any pre-existing muscle symptoms PRIOR to starting statin

Circulation. 2013 Nov.

statin tolerability
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
Possible Etiologies
  • Inhibition of Coenzyme Q10 production
  • Decreased cholesterol content in muscle cell membranes
coenzyme q 10
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
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 therapy1
Monitoring Statin Therapy
  • Check ALT (alanine aminotransferase) at baseline. Repeat only if symptoms of hepatotoxicity occur.

Circulation. 2013 Nov.

statins
Statins

2012: Removal of routine monitoring of liver enzymes from statin drug labels

statins1
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”
statins2
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 therapy2
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 therapy3
Monitoring Statin Therapy
  • “Monitor for new-onset diabetes”

Circulation. 2013 Nov.

another label change
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
Pravastatin
  • WOSCOPS: West of Scotland Coronary Prevention Study
  • 30% decrease in the incidence of DM in patients taking pravastatin
type 2 diabetes
Type 2 Diabetes

Statins 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
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 statin1
What if you can’t reach % reduction with statin?

Non-Statins???

“Don’t routinely use non-statins”

ezetimibe
Ezetimibe

Cholesterol absorption inhibitors

  • Can be combined with a statin
  • ENHANCE trial: Reductions in LDL and increases in HDL, BUT……..
ezetimibe1
Ezetimibe

ENHANCE Trial

  • Simvastatin plus ezetimibe vs. simvastatin
  • No change in primary outcome (carotid intima-media thickness)
hypertriglyceridemia
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!
hypertriglyceridemia1
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
Hypertension Management

Critical in preventing ASCVD!

unless you ve been in a cave
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
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
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 Societyof 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 guidelines1
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
“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
JNC 8: BP by Age

Start Pharmacotherapy* if BP exceeds:

*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
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
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
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
ASH: BP by Age

Start Pharmacotherapy if BP exceeds:

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

jnc 8 take home point
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
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 p oint
JNC 8 Take Home Point
  • Thiazides no longer “only” first line agent to treat HTN unless “compelling indications”
slide58

Hydrochlorothiazide

  • Most commonly prescribed diuretic for HTN in the world!
  • Starts working in about 2 hours
  • Half life 6-12 hours
  • Sulfa allergy precaution!!!
slide59

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!!!
slide60

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)
slide61

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
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?)
slide63

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 ClinHypertens (Greenwich) 2013 Dec 17. doi: 10.1111/jch.12237.

jnc 8 take home p oint1
JNC 8 Take Home Point
  • Thiazides no longer “only” first line agent to treat HTN unless “compelling indications”
htn in african americans
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
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 point1
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 Societyof Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich) 2013 Dec 17. doi: 10.1111/jch.12237.

accomplish trial
ACCOMPLISH Trial

Trial stopped early

ACE plus CCB

better than

ACE plus thiazide

Even though both had good BP control

Guess which thiazide? 

N Engl J Med 2008;359:2417-28.

accomplish trial1
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.

alpha and beta blockers
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
JNC 8: Chronic Kidney Disease

ACE or ARB even in African American

jnc 8 fyi
JNC 8 “FYI”

Wait 2-3 weeks before increasing medication or adding a new medication

jnc 8 fyi1
JNC 8 “FYI”

Can initiate treatment with two agents if systolic > 20 mmHg above goal; or diastolic > 10 mmHg above goal

jnc 8 fyi2
JNC 8 “FYI”

If more than 3 drug classes are needed to control BP, consider referral.

3 or more agents
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 agents1
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 agents2
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
jnc 8 fyi3
JNC 8 “FYI”

Do not add an ACE plus ARB to a medication regimen; either one or the other—NOT BOTH.

ace arb
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 arb1
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

statin drug class
Statin Drug Class
  • Statins are FIRST choice!
  • Statins are ONLY class to demonstrate reductions in mortality in primary and secondary prevention
thank you
Thank you!

To Reach me:

Amelie Hollier, DNP, FNP-BC, FAANP

Advanced Practice Education Associates

Lafayette, LA

[email protected]

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