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A CV Risk Education Symposium. Integrating Total CV Risk Management Into Clinical Practice. Welcome and Opening Remarks. What Is the PCE?.

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slide1

A CV Risk Education Symposium

Integrating Total CV Risk Management Into Clinical Practice

what is the pce
What Is the PCE?
  • The Practicing Clinicians Exchange (PCE) is an innovative network of live educational activities and home study materials designed for NPs and PAs. This unique CME/CE format will provide NPs and PAs with educational opportunities built to meet real-world clinical needs
  • The PCE’s goal is to provide practicing clinicians with comprehensive CME/CE programs in a variety of therapeutic areas, with opportunities to earn multiple CME/CE credits
what makes pce unique
What Makes PCE Unique?
  • Developed for NPs and PAs
  • Symposium series integrated with live teleconference series and home study workbook
  • Today’s symposium:
    • Is case based
    • Has been developed to meet your needs
    • Includes case studies led by NPs and PAs (in concert with expert physician faculty)
    • Includes full-panel Q&A sessions led by NPs and PAs
why are you here today

?

Why Are You Here Today?
  • Which of today’s learning objectives are you most interested in?

1. Explain the rationale for a global approach to CV risk management

2. Distinguish between primary and secondary CV risk management

3. Extrapolate data from recent clinical trials to select appropriate pharmacologic and nonpharmacologic treatment for CV risk factors in clinical practice

4. Apply current CV risk guidelines to clinical practice

5. Employ techniques to help patients achieve CV risk management goals

Use your keypad to vote now!

leading causes of death for all males and females united states 2002
Leading Causes of Death for All Males and Females: United States, 2002

Total CVD (preliminary)

Cancer

Accidents

Chronic Lower Respiratory Diseases

Diabetes Mellitus

Alzheimer’s Disease

494

500

434

400

289

300

269

Deaths (thousands)

200

100

69

61

64

42

39

34

0

Males

Females

CVD = cardiovascular disease. CDC/NCHS.

prevalence of chd by age and sex nhanes 1999 2002
Prevalence of CHD by Age and Sex:NHANES, 1999-2002

Males

Females

18

16.8

16

14

11.6

11.5

12

10.3

10

Percent of Population

8

6.3

6

3.6

4

3.0

1.6

1.4

2

0.2

0.3

0.0

0

20-34

35-44

45-54

55-64

65-74

75+

Ages

NHANES = National Health and Nutrition Examination Survey.CDC/NCHS and NHLBI.

prevalence of stroke by age and sex nhanes 1999 2002
Prevalence of Stroke by Age and Sex: NHANES, 1999-2002

Males

Females

14

12.0

11.5

12

10

8

Percent of Population

6.6

6.3

6

4

3.1

3.0

2.1

2

1.2

1.1

0.8

0.4

0.3

0

20-34

35-44

45-54

55-64

65-74

75+

Ages

CDC/NCHS and NHLBI.

estimated direct and indirect costs of cardiovascular diseases and stroke united states 2005
Estimated Direct and Indirect Costs of Cardiovascular Diseases and Stroke: United States, 2005

450

400

350

300

250

Billions of Dollars

200

150

100

50

0

HeartDisease

CoronaryHeartDisease

Stroke

Hyper-

tensiveDisease

Congestive

HeartFailure

Total CVD

AHA. Heart Disease and Stroke Statistics—2005 Update.

impact of elevated sbp and total cholesterol on chd mortality mrfit

64% lower

risk

59% lower

risk

91% lower

risk

Impact of Elevated SBP and Total Cholesterol on CHD Mortality: MRFIT

33.7

n = 202,620

Age-Adjusted CHD Death Rates

Per 10,000 Person-years

21

22.6

17.1

12.7

12.2

17.7

12.3

9.6

8.3

245

16.7

5.9

10.9

8.5

221–244

6.3

5.5

13.7

7.9

7.9

203–220

Cholesterol

Quintile (mg/dL)

6

4.3

182–202

5.6

5

3.4

3.1

<182

142

<118

132–141

125–131

118–124

SBP Quintile (mm Hg)

MRFIT= Multiple Risk Factor Intervention Trial;SBP = systolic blood pressure.

Adapted from Neaton JD, et al. Arch Intern Med. 1992;152:56-64.

risk of chd in mild hypertension by intensity of associated risk factors
Risk of CHD in Mild Hypertension by Intensity of Associated Risk Factors

40

42

36

30

21

10-Year Probability of Event (%)

24

18

14

10

12

6

4

6

0

Risk Factors

SBP 150-160 mm Hg + + + + + +

TC 240-262 mg/dL − + + + + +

HDL-C 33-35 mg/dL − − + + + +

Diabetes − − − + + +

Cigarette smoking − − − − + +

ECG-LVH − − − − − +

Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S.

integrated cellular mechanisms of cvd
Integrated Cellular Mechanisms of CVD

Hypertension

Dyslipidemia

Diabetes

Endothelial Dysfunction

 COX Activity

 Endothelin

 Inflammation

 NO Synthesis

  • Vasoconstriction
  • Thrombosis
  • Superoxide
  • Leukocyte adhesion
  • Endothelial permeability
  • Foam cell formation
  • T-cell activation
  • Vasoconstriction
  • Calcium mobilization
  • Thromboxane A2
  • Prostaglandin H2
  • Prostacyclin

NO = nitric oxide; COX = cyclooxygenase.

Liao JK. Clin Chem. 1998;44:1799-1808. Libby P. J Intern Med. 2000;247:349-358. Mason RP. Cerebrovasc Dis. 2003;16(suppl 3):11-17.

ascot study design

ASCOT-BPLA

Results reported in 2005

19,257 hypertensive patients (BPLA)

amlodipine ±perindopril

atenolol ± bendroflumethiazide

PROBE

design

ASCOT-LLA

Results reported in 2003

10,305 patients (LLA)

TC ≤6.5 mmol/L (251 mg/dL)

5168 patients

atorvastatin 10 mg

5137 patients

placebo

Double-blind

ASCOT: Study Design

Investigator-led, multinational randomized controlled trial

ASCOT = Anglo-Scandinavian Cardiac Outcomes Trial; BPLA = blood pressure–lowering arm; LLA = lipid-lowering arm; PROBE = prospective randomized open blinded end points.

Adapted from Sever PS, et al, for the ASCOT Investigators. J Hypertens. 2001;19:1139-1147.

ascot patient population risk factor profile

Hypertension

Aged ≥55 years

Male

Microalbuminuria/proteinuria

Smoker

Family history of CHD

Plasma TC:HDL-C ≥6

Type 2 diabetes

Certain ECG abnormalities

LVH

Prior cerebrovascular events

Peripheral vascular disease

0

10

20

30

40

50

60

70

80

90

100

Patients With Risk Factor (%)

ASCOT: Patient Population Risk Factor Profile

All patients in ASCOT had hypertension plus ≥3 risk factors for CHD

ECG = electrocardiogram; LVH = left ventricular hypertrophy; TC = total cholesterol.

Sever PS, et al, for the ASCOT Investigators. J Hypertens. 2001;19:1139-1147.

ascot main outcome measure
ASCOT: Main Outcome Measure
  • Combination of nonfatal MI and fatal CHD
  • Results to be discussed later today

MI = myocardial infarction.

Sever PS, et al, for the ASCOT Investigators. J Hypertens. 2001;19:1139-1147.

action to control cardiovascular risk in diabetes accord trial
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
  • Randomized, multicenter clinical trial (75 sites in US and Canada), 2x2 factorial design
  • 10,000 patients with type 2 diabetes (with and without existing CVD) at high risk for CVD events
  • Will independently test 3 medical strategies to reduce CVD in patients with diabetes

A1C = glycosylated hemoglobin. Available at: www.accordtrial.org/public/purpose.cfm.

accord main outcome measure
ACCORD: Main Outcome Measure
  • First occurrence after randomization of a major CVD event
    • Nonfatal MI
    • Nonfatal stroke
    • CV death
  • Results to be published in 2010

Available at:www.accordtrial.org/public/purpose.cfm.

primary and secondary prevention definitions
Primary and Secondary Prevention: Definitions
  • Primary prevention
    • Modification of risk factors or prevention of their development to prevent or delay the onset of CHD
  • Secondary prevention
    • Initiation of therapy to reduce recurrent CHD events and decrease cardiac mortality in patients with established CHD
  • “Primary and a half prevention”*
    • As patients with subclinical CHD are identified, the distinction between primary and secondary prevention becomes blurred

*Celermajer DS. JACC. 2005;45:1994-1996.

key goals jnc 7 ncep ada and aha guidelines
Key Goals: JNC 7, NCEP, ADA, and AHA Guidelines

*For patients with diabetes. †Therapeutic option <100 mg/dL for patients at moderately high risk. ‡Therapeutic option <70 mg/dL for patients at very high risk.

American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S15-S35;S65-S67;S68-S71; Chobanian AV, et al. JNC 7: Complete Report. 2003. Available at: http://hyper.ahajournals.org/cgi/content/full/42/6/1206; Grundy SM et al. Circulation. 2004;110:227-239; NCEP ATP III. 2002. NIH Publication No. 02-5215; Pearson TA, et al. Circulation. 2002;106:388-391.

acc aha abc approach to primary and secondary prevention
ACC/AHA ABC Approach to Primary and Secondary Prevention

Complete sets of ACC/AHA guidelines available at www.acc.org and www.americanheart.org.Gluckman TJ, et al. Arch Intern Med. 2004;164:1490-1500.

cv risk factor evaluation what to consider
CV Risk Factor Evaluation: What to Consider
  • “Traditional” risk factors
  • Framingham risk analysis
  • Metabolic syndrome
  • Atherosclerotic disease (or equivalence)
  • “Emerging” risk factors?

More on these in the presentations to come!

conclusions the case for total cv risk management
Conclusions: The Case for Total CV Risk Management
  • CV disease remains the leading cause of death in both men and women in the US
  • Framingham data show that CV risk factors tend to cluster—and that risk of death from CHD and stroke increases proportionately
  • Endothelial dysfunction seems to be a key factor in the development of CV disease
  • Recent clinical trials have given us a wealth of information with which to manage total CV risk and have led to updates of major clinical guidelines
hypertension affects approximately 65 million americans 28 of adults
Hypertension Affects Approximately 65 Million Americans: 28% of Adults

50

Males

Females

40%

38%

40

29%

28%

27%

27%

30

Population With Hypertension (%)

20

10

0

Non-Hispanic White

Non-Hispanic Black

Mexican American

Fields LE, et al. Hypertension. 2004;44:398-404.

blood pressure lower is better

256

256

128

128

64

64

32

32

16

16

8

8

4

4

2

2

1

1

0

0

120

140

160

180

70

80

90

100

110

Blood Pressure: Lower Is Better

Ischemic Heart Disease Mortality

Age at Risk (Y)

Age at Risk (Y)

80-89

80-89

70-79

70-79

60-69

60-69

50-59

50-59

40-49

40-49

Ischemic Heart Disease Mortality

Ischemic Heart Disease Mortality

Usual Systolic BP (mm Hg)

Usual Diastolic BP (mm Hg)

BP = blood pressure.

Prospective Studies Collaboration. Lancet. 2002;360:1903-1913.

jnc 7 blood pressure classification
JNC 7 Blood Pressure Classification

SBP DBP (mm Hg) (mm Hg)

Normal <120 and <80

Prehypertension 120-139 or 80-89

Stage 1 hypertension 140-159 or 90-99

Stage 2 hypertension ≥160 or ≥100

DBP = diastolic blood pressure.

Chobanian AV, et al. JNC 7: Complete Report. 2003.Available at: http://hyper.ahajournals.org/cgi/content/full/42/6/1206.

jnc 7 goal blood pressures
JNC 7 Goal Blood Pressures
  • Most patients
    • <140/90 mm Hg
  • Patients with diabetes or chronic kidney disease
    • <130/80 mm Hg
    • Based mostly on observational data, not prospective clinical trials
  • Patients with metabolic syndrome
    • No specific recommendation

Chobanian AV, et al. JNC 7: Complete Report. 2003.Available at: http://hyper.ahajournals.org/cgi/content/full/42/6/1206.

jnc 7 algorithm for hypertension

Stage 2 Hypertension

2-drug combinations for most (usually thiazide-type diuretics and ACEI, or ARB, or BB, or CCB).

Drug(s) for Compelling Indications

Other antihypertensive drugs (diuretic, ACEI, ARB, BB, CCB) as needed.

Stage 1 Hypertension

Thiazide-type diuretics for most; may consider ACEI, ARB, BB, CCB, or combination.

JNC 7: Algorithm for Hypertension

LIFESTYLE MODIFICATIONS

Not at goal BP (<140/90 mm Hg or <130/80 mm Hg for patients with diabetes or chronic kidney disease)

INITIAL DRUG CHOICES

With Compelling Indications

Without Compelling Indications

If not at goal BP, optimize dosages or add additional drugs until

goal BP is achieved. Consider consultation with hypertension specialist.

Chobanian AV, et al. JNC 7: Complete Report. 2004. Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.

practicing clinicians case study 1 a 33 year old white man who presents with acute back pain
Practicing Clinicians Case Study 1: A 33-Year-Old White Man Who Presents With Acute Back Pain
  • Presents with acute low back pain following weekend racquetball game
  • No other complaints
  • “Weekend warrior” lifestyle; nonsmoker; occasional ETOH
  • Using this presentation to perform a CV risk assessment, you find
    • BP:
      • 148/90 mm Hg (first reading)
      • 146/88 mm Hg (second reading)
    • Height: 6' 0"; weight: 218 lb; waist: 39"
  • You treat the acute low back pain and ask the patient to return for a more thorough evaluation of CV status
practicing clinicians case study 1 findings during return visit
Practicing Clinicians Case Study 1: Findings During Return Visit
  • Family history not significant for CV disease
  • High-sodium, high-fat diet
  • Laboratory findings
    • TC: 170 mg/dL
    • LDL-C: 102 mg/dL
    • HDL-C: 48 mg/dL
    • TG: 100 mg/dL
    • Fasting glucose: 96 mg/dL
    • Serum creatinine: 0.9 mg/dL (GFR: 128 mL/min/1.73 m2)
    • Dipstick: negative for protein

GFR = glomerular filtration rate.

practicing clinicians case study 1 decision point

?

Practicing Clinicians Case Study 1: Decision Point
  • Given the patient’s risk factor profile, how would you treat him?

1. Prescribe diet/exercise regimen and determine in 3 to 4 months whether drug therapy is indicated

2. Start a diuretic

3. Start a diuretic and an ACE inhibitor

4. Start a dihydropyridineCCB

Use your keypad to vote now!

ACE = angiotensin-converting enzyme; CCB = calcium channel blocker.

jnc 7 lifestyle modifications to prevent and manage hypertension
JNC 7: Lifestyle Modifications to Prevent and Manage Hypertension

DASH = Dietary Approaches to Stop Hypertension.

Chobanian AV, et al. JNC 7: Complete Report. 2003. Available at: http://hyper.ahajournals.org/cgi/content/full/42/6/1206.

practicing clinicians case study 1 decision point40

?

Practicing Clinicians Case Study 1: Decision Point
  • The patient tells you he has been toostressed with work and family obligations to seriously follow his diet/exercise regimen. What would you do next?

1. Start a -blocker

2. Start a diuretic

3. Start a diuretic and an ACE inhibitor

4. Start a dihydropyridineCCB

Use your keypad to vote now!

practicing clinicians case study 1 cv risk management pearls
Practicing Clinicians Case Study 1: CV Risk Management Pearls
  • Lifestyle modifications alone may be sufficient for a young patient with stage 1 hypertension and no other CV risk factors (expert opinion)
  • If lifestyle modifications do not achieve goal BP within 3-4 months, pharmacologic therapy can be prescribed (expert opinion)
  • Excellent clinical trial outcome data prove that lowering BP with several classes of drugs, including ACEIs, ARBs, β-blockers, CCBs, and thiazide-type diuretics, will all reduce the complications of hypertension (JNC 7)

ARB = angiotensin receptor blocker.

newer versus older agents allhat
Newer Versus Older Agents: ALLHAT

Primary End Point: Fatal CHD or Nonfatal MI

16

Chlorthalidone

Amlodipine

Lisinopril

N = 33,357

12

Cumulative Event Rate (%)

8

4

0

0

1

2

3

4

5

6

7

Time to Event (years)

ALLHAT = Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-2997.

newer versus older antihypertensive agents ascot bpla
Newer Versus Older Antihypertensive Agents: ASCOT-BPLA

Primary End Point: Nonfatal MI and Fatal CHD

Atenolol-based regimen No. of events: 474 Amlodipine-based regimen No. of events: 429

5.0

4.0

Proportion of Events (%)

3.0

2.0

HR = 0.90 (0.79­1.02)P = .1052*

N = 19,257

1.0

0.0

0.0

1.0

2.0

3.0

4.0

5.0

Years

*Trial stopped early, after 5.5 years’ median follow-up

Dahlöf B, et al, for the ASCOT Investigators. Lancet. 2005;366:895-906.

ascot bpla summary of all end points
ASCOT-BPLA: Summary of All End Points

Unadjusted Hazard Ratio (95% CI)

0.90 (0.79-1.02)

0.87 (0.76-1.00)

0.87 (0.79-0.96)

0.84 (0.78-0.90)

0.89 (0.81-0.99)

0.76 (0.65-0.90)

0.77 (0.66-0.89)

0.84 (0.66-1.05)

1.27 (0.80-2.00)

0.68 (0.51-0.92)

0.98 (0.81-1.19)

0.65 (0.52-0.81)

1.07 (0.62-1.85)

0.70 (0.63-0.78)

0.85 (0.75-0.97)

0.86 (0.77-0.96)

0.84 (0.76-0.92)

Primary Nonfatal MI (including silent) + fatal CHD

SecondaryNonfatal MI (excluding silent) + fatal CHD

Total coronary end pointTotal CV events and proceduresAll-cause mortalityCV mortalityFatal and nonfatal strokeFatal and nonfatal heart failure

Tertiary Silent MI

Unstable anginaChronic stable anginaPeripheral arterial diseaseLife-threatening arrhythmiasNew-onset diabetes mellitusNew-onset renal impairment

Post hoc

Primary end point + coronary revasc procs

CV death + MI + stroke

1.00

1.45

2.00

0.50

0.70

Atenolol-based regimen better

Amlodipine-based regimen better

Area of the yellow squares is proportional to the amount of statistical information.

Dahlöf B, et al, for the ASCOT Investigators. Lancet. 2005;366:895-906.

practicing clinicians case study 2 49 year old white woman with resistant hypertension
Practicing Clinicians Case Study 2: 49-Year-Old White Woman With “Resistant” Hypertension
  • Presents for routine follow-up of BP
  • Family history: type 2 diabetes; father had MI (age 45)
  • Nonsmoker; no ETOH use; history of cystic renal disease
  • Physical examination
    • BP: 158/95 mm Hg
    • Height: 5' 6"; weight: 142 lb; waist: 34"
  • Laboratory values
    • Lipid profile: within normal limits
    • TG: 144 mg/dL
    • Fasting glucose: 98 mg/dL
    • Serum creatinine: 1.3 mg/dL (GFR: 44 mL/min/1.73 m2)
    • Dipstick: negative for protein
  • Medication
    • Enalapril 40 mg/d
practicing clinicians case study 2 decision point

?

Practicing Clinicians Case Study 2: Decision Point
  • Given this patient’s risk factor profile, what goal would you have for her BP?

1. <140/90 mm Hg

2. <130/85 mm Hg

3. <130/80 mm Hg

4. <120/80 mm Hg

Use your keypad to vote now!

practicing clinicians case study 2 decision point47

?

Practicing Clinicians Case Study 2: Decision Point
  • Because the patient has chronic renal disease, the BP goal is <130/80 mm Hg. What would you do to get this patient there?

1. Reemphasize diet/exercise therapy and reevaluate in 3 months

2. Switch from an ACE inhibitor to an ARB

3. Add a thiazide diuretic

4. Add a dihydropyridine CCB

Use your keypad to vote now!

practicing clinicians case study 2 cv risk management pearls
Practicing Clinicians Case Study 2: CV Risk Management Pearls
  • If BP is >20/10 mm Hg above goal, consider starting with 2 agents, perhaps in a combination pill
  • If patient still not at goal BP, optimize dosages or add additional drugs until goal is achieved
  • “Compelling indications” may dictate treatment choices

Chobanian AV, et al. JNC 7: Complete Report. 2003. Available at: http://hyper.ahajournals.org/cgi/content/full/42/6/1206.

esh esc guidelines effective combinations of antihypertensive agents
ESH-ESC Guidelines: Effective Combinations of Antihypertensive Agents

Diuretics

Angiotensin ReceptorAntagonists

β-Blockers

CalciumAntagonists

α-Blockers

ACE Inhibitors

ESH = European Society of Hypertension; ESC = European Society of Cardiology.

Adapted from ESH-ESC Guidelines Committee. J Hypertens. 2003;21:1011-1053.

jnc 7 compelling indications for antihypertensive drug classes
JNC 7: Compelling Indications for Antihypertensive Drug Classes

Recommended Drugs

AldoCompelling Indication Diuretic BB ACEI ARB CCB ANT

Heart failure • • • •   •

Post MI   • •     •

High coronary disease risk • • •   •  

Diabetes • • • • •  

Chronic kidney disease     • •    

Recurrent stroke prevention •   •      

Aldo ANT = aldosterone antagonist.

Chobanian AV, et al. JNC 7: Complete Report. 2004. Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.

practicing clinicians case study 2 decision point51

?

Practicing Clinicians Case Study 2: Decision Point
  • You add a thiazide diuretic to the ACE inhibitor regimen, but BP is still >130/80 mm Hg. What would you do now?

1. Maximize dosage of diuretic and reevaluate in 3 months

2. Add a CCB to the current regimen

3. Add an ARB to the current regimen

4. Add an aldosterone blocker to the current regimen

Use your keypad to vote now!

practicing clinicians case study 2 cv risk management pearls52
Practicing Clinicians Case Study 2: CV Risk Management Pearls
  • Addition of a thiazide diuretic markedly improves the response to -blockers, ACE inhibitors, ARBs, and CCBs, especially in salt-sensitive populations
    • Has been some concern about thiazide diuretics and increased risk for diabetes
  • Addition of a CCB would be another option for this patient

Chobanian AV, et al. JNC 7: Complete Report. 2003. Available at: http://hyper.ahajournals.org/cgi/content/full/42/6/1206.

multiple antihypertensive agents are needed to achieve target bp allhat
Multiple Antihypertensive Agents Are Needed to Achieve Target BP: ALLHAT

% Controlled <140/90 mm Hg

1 Drug

2 Drugs

3 Drugs

100

80

60

Percentage of Patients

40

20

0

Baseline

6 Months

3 Years

5 Years

1 Year

Adapted from Cushman WC, et al. J Clin Hypertens. 2002;4:393-404.

practicing clinicians case study 2 cv risk management pearls54
Practicing Clinicians Case Study 2: CV Risk Management Pearls
  • If goal BP is not achieved despite use of 3-drug regimen that includes a diuretic, consider:
    • Pseudoresistance: white coat, wrong cuff
    • Nonadherence
    • Volume overload: excess salt intake, progressive renal damage, inadequate diuretic therapy
    • Drug-related causes: dosages too low, wrong type of diuretic, use of short-acting drugs, drug interactions, NSAIDs, sympathomimetics, “alternative” therapies, illicit drugs, etc
    • Treatable causes: sleep apnea, renovascular disease, coarctation of aorta, glucocorticoid excess states, etc

Chobanian AV, et al. JNC 7: Complete Report. 2003. Available at: http://hyper.ahajournals.org/cgi/content/full/42/6/1206.

jnc 7 guidelines for measurement of bp
JNC 7 Guidelines for Measurement of BP

Chobanian AV, et al. JNC 7: Complete Report. 2003. Available at: http://hyper.ahajournals.org/cgi/content/full/42/6/1206.

how will jnc 8 differ from jnc 7
How Will JNC 8 Differ From JNC 7?
  • Will <140/90 (or <130/80) mm Hg still be considered “normal” blood pressure?
  • Will ASCOT-BPLA change the initial approach to therapy? For example:
    • Should CCBs and ACEIs be preferred as initial therapy over BBs and diuretics?
    • Should we avoid starting therapy with a BB or diuretic in patients at metabolic risk for diabetes?
conclusion practicing clinicians hypertension cases
Conclusion: Practicing Clinicians Hypertension Cases
  • Consider every office visit an opportunity to screen for CV risk factors—regardless of the presenting complaint
  • Counsel patients with hypertension and other CV risk factors on health-promoting lifestyle modifications
  • Compelling indications may warrant use of specific agents (eg, ACEIs, ARBs, -blockers, CCBs, diuretics)
  • Treatment with 2 or more agents is particularly important to control BP in high-risk patients
an invitation to participate in our np pa market research program
An Invitation to Participate in Our NP/PA Market Research Program
  • Participate in our market research program during the break and receive a free PCE computer mouse!
lipoprotein classes
Lipoprotein Classes

Chylomicrons, VLDL, and their catabolic remnants

LDL

HDL

>30 nm

20–22 nm

9–15 nm

Potentially

pro-inflammatory

Potentially

anti-inflammatory

VLDL = very low density lipoprotein.

Cockerill GW, et al. Arterioscler Thromb Vasc Biol. 1995;15:1987-1994; Colome C, et al. Atherosclerosis. 2000;149:295-302; Doi H, et al. Circulation. 2000;102:670-676.

national cholesterol education program ncep management guidelines
National Cholesterol Education Program (NCEP) Management Guidelines
  • Obtain a fasting lipid profile in all patients. For those who have had an MI, obtain a fasting lipid profile within 24 hours of admission
  • Start therapeutic lifestyle changes in all patients, including:
    • Reduced intakes of saturated fats (<7% of total calories) and cholesterol (<200 mg/d)
    • Increased physical activity
    • Weight reduction
    • Add plant stanols/sterols (2 g/d) and viscous fiber (10-25 g/d) to enhance LDL-C lowering

NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/.

ncep management guidelines cont d
NCEP Management Guidelines (cont’d)
  • For primary and secondary prevention, use statins first-line to achieve LDL-C goal
  • If patient remains above LDL-C goal, intensify statin therapy—and add a second LDL-C–lowering agent, if needed
  • If TG 150 mg/dL or HDL-C <40 mg/dL:
    • Emphasize weight management, physical activity, smoking cessation
  • If TG 200-499 mg/dL after initiation of LDL-C–lowering therapy:
    • Calculate non-HDL-C as secondary target
    • Consider adding nicotinic acid or a fibrate
  • If TG 500 mg/dL
    • Very low-fat diet, weight reduction, increased physical activity
    • Consider treating with nicotinic acid or a fibrate before LDL-C–lowering therapy

NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/.

risk profile assessment for ldl c lowering
Risk Profile Assessment for LDL-C Lowering

Use a risk assessment tool* for patients with 2 RFs

10-year CHD Risk

0

10%

20%

0-1 RF

2 RFs

CHD or Risk Equivalent†

*Such as the Framingham Risk Score (FRS).

†Includes diabetes, non-coronary atherosclerotic vascular disease, and 20% 10-year CHD risk by the FRS.

NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/.

major independent chd risk factors
Major Independent CHD Risk Factors
  • Cigarette smoking
  • BP ≥140/90 mm Hg (or taking antihypertensive medication)
  • Low HDL-C (<40 mg/dL)
  • Family history of premature CHD
    • <55 years in first-degree male relative
    • <65 years in first-degree female relative
  • Age
    • Men ≥45 years
    • Women ≥55 years

Grundy SM, et al. Circulation. 2004;110:227-239; NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/.

chd risk equivalents point to 20 10 year risk for a chd event
CHD Risk “Equivalents” Point to >20% 10-year Risk for a CHD Event
  • Diabetes
  • Other clinical atherosclerotic disease
    • Peripheral arterial disease
    • Abdominal aortic aneurysm
    • Carotid artery disease
  • ≥2 risk factors with 10-year risk for hard CHD >20%

Grundy SM, et al. Circulation. 2004;110:227-239; NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/.

practicing clinicians case study 3 44 year old hispanic man who wants to quit smoking
Practicing Clinicians Case Study 3: 44-Year-Old Hispanic Man Who Wants to Quit Smoking
  • Wife and children are “hassling” him to quit smoking
  • 22 pack-year history; has tried to quit several times in recent years
  • Father died of MI at age 53
  • Physical examination
    • Height 5'8"; weight 164 lb; waist 34"
    • BP: 160/95 mm Hg on first reading, 158/91 mm Hg on second reading
    • Lungs clear to auscultation
practicing clinicians case study 3 decision point

?

Practicing Clinicians Case Study 3: Decision Point
  • What would be your best next step in this case?

1. Order a lipid profile

2. Order advanced lipid testing to evaluate LDL-C particle size and number

3. Order a 2-hr postprandial glucose test

4. Order EBCT to assess coronary calcium

Use your keypad to vote now!

EBCT = electron beam computed tomography.

practicing clinicians case study 3 laboratory values
Practicing Clinicians Case Study 3: Laboratory Values
  • Lipid profile
    • TC 205 mg/dL; LDL 140 mg/dL; HDL 40 mg/dL; TG 125 mg/dL
  • Other laboratory values
    • Glucose 91 mg/dL (fasting)
    • Creatinine 1.2 mg/dL (GFR: 68 mL/min/1.73 m2)
    • UA negative for protein
practicing clinicians case study 3 decision point71

?

Practicing Clinicians Case Study 3: Decision Point
  • Is this patient a candidate for lipid-loweringtherapy?

1. Yes

2. No

Use your keypad to vote now!

practicing clinicians case study 3 risk for fatal or nonfatal chd over the next 10 years in men
Practicing Clinicians Case Study 3: Risk for Fatal or Nonfatal CHD Over the Next 10 Years in Men*

*A separate Framingham risk calculator exists for women.

NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/.

practicing clinicians cv management pearls disadvantages of framingham risk calculator
Practicing Clinicians CV Management Pearls: Disadvantages of Framingham Risk Calculator
  • Lack of sensitivity for patients with:
    • A severe single risk factor
    • Multiple lifestyle risk factors
    • Metabolic syndrome
    • Presence of emerging risk factors
  • Overestimates the risk of age
  • May underestimate risk in women
  • Does not predict risk of stroke
ascot lla clinical question
ASCOT-LLA: Clinical Question
  • Is atorvastatin 10 mg/d, when compared with placebo, beneficial for primary prevention of CHD in patients treated for hypertension who are not conventionally deemed dyslipidemic and who have at least 3 additional CV risk factors?

ASCOT-LLA = Anglo-Scandinavian Cardiac Outcomes Trial─Lipid Lowering Arm.

Sever PS, et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158.

ascot lla primary end point nonfatal mi and fatal chd in patients with treated hypertension
ASCOT-LLA: Primary End Point (Nonfatal MI and Fatal CHD) in Patients With Treated Hypertension

4

Placebo No. of events: 154

Atorvastatin 10 mg/d No. of events: 100

36%

3

Cumulative Incidence (%)

2

1

HR=0.64 (95% CI, 0.50-0.83)

P=.0005*

0

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Years

*Trial stopped early, after 3.3 years’ median follow-up

Sever PS, et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158.

ascot lla secondary end points
ASCOT-LLA: Secondary End Points

Fatal and Nonfatal Stroke

All CV Events and Procedures

All Coronary Events

No. of events

No. of events

No. of events

Placebo 121

Placebo 486

Placebo 247

Atorvastatin 10 mg 89

Atorvastatin 10 mg 389

Atorvastatin 10 mg 178

6

12

3

5

10

27%

21%

29%

4

8

2

Cumulative Incidence (%)

3

6

2

4

1

P = .0236

P = .0005

P = .0005

1

2

HR = 0.73 (CI, 0.56-0.96)

HR = 0.79 (CI, 0.59-0.90)

HR = 0.71 (CI, 0.59-0.86)

0

0

0

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Years

Years

Years

Sever PS, et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158.

practicing clinicians case study 3 cv risk management pearls
Practicing Clinicians Case Study 3: CV Risk Management Pearls
  • Recall that the majority of patients with hypertension have at least 2 additional risk factors
  • Make a full assessment of all treatable risk factors, including lipid and glucose metabolism
  • For patients with hypertension and at least 3 additional CV risk factors (eg, BP ≥140/90 mm Hg, smoking, low HDL-C, family history of premature CHD), NCEP ATP III update recommends an optional LDL-C goal <100 mg/dL in addition to BP and other CV risk management

Glazer NL, et al. Am J Hypertens. 2005;18:759-766; Grundy SM, et al. Circulation. 2004;110:227-239;Pearson TA, et al. Circulation. 2002;106:388-391; Sever PS, et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158; Williams B. J Am Coll Cardiol. 2005;45:813-827.

therapeutic goals for ldl c at various risk levels ncep atp iii and ncep 2004
Therapeutic Goals for LDL-C at Various Risk Levels: NCEP ATP III and NCEP 2004

Grundy SM, et al. Circulation. 2004;110:227-239; NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/.

ncep atp iii update 2004 new risk levels
NCEP ATP III Update (2004): New Risk Levels

Risk Level

Risk Factors

Very high risk

Moderately high risk

Established CVD + multiple risk factors (diabetes; continued cigarette smoking; metabolic syndrome; acute coronary syndrome)

Advancing age; >2 risk factors (continued cigarette smoking; strongly positive family history of premature atherosclerotic CVD; high TG, elevated non–HDL-C; low HDL-C; metabolic syndrome; emerging risk factors)

Grundy SM, et al. Circulation. 2004;110:227-239.

ncep atp iii classification of other lipoprotein levels
NCEP ATP III Classification of Other Lipoprotein Levels

Total Cholesterol

HDL-Cholesterol*

*AHA recommends ≥40 in men and ≥50 in women

Triglycerides

Pearson TA, et al. Circulation. 2002;106:388-391.NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/.

coronary artery calcification as assessed by ebct
Coronary Artery Calcification as Assessed by EBCT

Severe Calcification

No Calcification

LAD

LCX

Left Main

practicing clinicians case study 4 a 77 year old african american woman with recent acute mi
Practicing Clinicians Case Study 4: A 77-Year-Old African American Woman With Recent Acute MI
  • 77-year-old African American woman, S/P AMI 1 week ago
  • PMHx: ASHD, HTN, osteoarthritis
  • Presents for routine evaluation after hospital discharge
  • V/S: T 98.4oF orally, P 72, R 18, BP 135/92 mm Hg, SaO2 92% RA, BMI 24
  • Current medications:
    • Metoprolol 100 mg qd, HCTZ 25 mg qd, ASA 81 mg qd, atorvastatin 20 mg qd
practicing clinicians case study 4 additional patient data
LFTs:

AST 24 u/L

ALT 20 u/L

Lipid panel:

TC 180 mg/dL

TG 138 mg/dL

LDL-C 101 mg/dL

HDL-C 43 mg/dL

Practicing Clinicians Case Study 4: Additional Patient Data
  • Basic Metabolic Panel:
    • Fasting glucose 89 mg/dL
    • BUN 13 mg/dL
    • Creatinine 0.6 mg/dL
    • Sodium 136 meq/dL
    • Potassium 4.0 meq/dL
    • Chloride 98 meq/dL
    • CO2 27 meq/dL
  • CBC:
    • WBC 6.6 THDS/CMM
    • Hemoglobin 12.9 g/dL
    • Hematocrit 37.1%
    • Platelets 234 THDS/CMM
practicing clinicians case study 4 decision point

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Practicing Clinicians Case Study 4: Decision Point
  • What should you consider first?

1. Order a high-sensitivity CRP test

2. Perform 10-year Framingham risk assessment

3. Aggressively escalate statin dosage to lower LDL-C below 70 mg/dL

4. Counsel patient regarding target lifestyle changes and advise that you will re-evaluate her in 3 to 6 months

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prove it timi 22 clinical question
PROVE-IT–TIMI 22: Clinical Question
  • Does intensive lipid-lowering with atorvastatin 80 mg/d provide greater protection against death or major CV events than standard lipid-lowering with pravastatin 40 mg/d in patients who recently had an ACS?

ACS = acute coronary syndrome; PROVE-IT–TIMI 22 = Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22.

Cannon C, et al. N Engl J Med. 2004;350:1495-1504.

prove it timi 22 primary end point death from any cause or major cv event
PROVE IT–TIMI 22 Primary End Point: Death From Any Cause or Major CV Event

30

Pravastatin 40 mg/d (26.3%)

16%

25

20

Atorvastatin 80 mg/d (22.4%)

15

Patients With Event (%)

10

16% HRR (95% CI, 5%-26%)

P = .005

5

0

0

3

6

9

12

15

18

21

24

27

30

N = 4162

Follow-up (months)

HRR = hazard ratio reduction.

Cannon CP, et al. N Engl J Med. 2004;350:1495-1504.

reversal clinical question
REVERSAL: Clinical Question
  • Does intensive lipid-lowering therapy with atorvastatin 80 mg/d, when compared with moderate lipid-lowering therapy with pravastatin 40 mg/d, reduce the progression of coronary atherosclerosis?

REVERSAL = Reversal of Atherosclerosis with Aggressive Lipid Lowering.

Nissen SE, et al, for the REVERSAL Investigators. JAMA. 2004;291:1071-1080.

reversal primary end point percentage change in atheroma volume
REVERSAL Primary End Point: Percentage Change in Atheroma Volume

P = .02

3.0

2.7%†

2.5

2.0

1.5

Median Change in Atheroma Volume (%)

1.0

0.5

0

-0.5

-0.4%*

-1.0

Atorvastatin (80 mg/d)

(n = 253)

Pravastatin (40 mg/d)

(n = 249)

*No progression vs baseline (P = .98).

†Net progression vs baseline (P = .001).

Nissen SE, et al, for the REVERSAL Investigators. JAMA. 2004;291:1071-1080.

mrc bhf heart protection study hps clinical question
MRC/BHF Heart Protection Study (HPS): Clinical Question
  • Does simvastatin 40 mg/d, when compared with placebo, cause a significant reduction in CHD events in patients at high risk (eg, because of prior MI, diabetes, hypertension)?

BHF = British Heart Foundation; CHD = coronary heart disease; MI = myocardial infarction; MRC = Medical Research Council.

HPS Collaborative Group. Lancet. 2002;360:7-22.

hps key findings
HPS: Key Findings

CHDEvents

All-causeMortality

5

0

–5

Average Change From Baseline at End of Study (%)

–10

–15

–13%

P = .0003

–20

–25

–30

–27%

N = 20,536

P <.0001

HPS Collaborative Group. Lancet. 2002;360:7-22.

ctt meta analysis cause specific mortality per mmol l ldl c reduction
CTT Meta-analysis: Cause-Specific Mortality per mmol/L LDL-C Reduction

Events

Cause of Death

Risk Reduction (CI)

Treatment(45,054)

Control

(45,002)

Vascular causes:

CHD

1548 (3.4%)

1960 (4.4%)

0.81 (0.76-0.85)

Stroke

Other vascular

265 (0.6%)

289 (0.6%)

291 (0.6%)

302 (0.7%)

0.91 (0.74-1.11)

0.95 (0.78-1.16)

Any non-CHDvascular

0.93 (0.83-1.03)

593 (1.3%)

554 (1.2%)

0.83 (0.79-0.87)

Any vascular

2553 (5.7%)

2102 (4.7%)

0.95 (0.90-1.01)

Any non-vascular

1801 (4.0%)

1730 (3.8%)

0.88 (0.84-0.91)

Any death

4354 (9.7%)

3832 (8.5%)

0.5

1.0

1.5

Treatment Better

Control Better

Effect P <.0001

CTT = Cholesterol Treatment Trialists.

Baigent C, et al; Cholesterol Treatment Trialists’ Collaborators. Lancet. 2005;366:1267-1278.

practicing clinicians case study 4 decision point92

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Practicing Clinicians Case Study 4: Decision Point
  • You elect to titrate the statin upward to lower LDL-C below 70 mg/dL. However, the patient complains of minor muscle aches. What should you do now?

1. Stop the statin immediately

2. Reduce the statin dose back to 20 mg qd

3. Keep the patient on the statin at the increased dose and order a CK

4. Immediately refer the patient to a cardiologist

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practicing clinicians case study 4 decision point93

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Practicing Clinicians Case Study 4: Decision Point
  • The CK results are 460 ng/dL. Should you

1. Stop the statin immediately?

2. Give the patient a 3-week washout period and then attempt to re-start the statin?

3. Return the patient to the initial, lower statin dose?

4. Keep the patient on the statin, and advise her of the increased risk and the need for more frequent monitoring?

Use your keypad to vote now!

practicing clinicians case study 4 cv risk management pearls rhabdomyolysis
Practicing Clinicians Case Study 4: CV Risk Management Pearls—Rhabdomyolysis
  • CK levels must rise >10-fold for risk of stopping statin therapy to outweigh benefit
    • More than 474,468,000 Rx written for statins through 2001 (excluding cerivastatin)
    • 42 cases of fatal rhabdomyolysis reported (excluding cerivastatin)
  • ~ 2 cases of minor rhabdomyolysis per 1,000 statin patients, none requiring treatment
    • Discontinuation rates due to elevated CK
      • <1 per 10,000
  • Fatal rhabdomyolysis incidence <1 per 1,000,000

Staffa JA, et al. N Engl J Med. 2002;346:539-540.

emerging risk factors lipid and non lipid
Inflammatory markers (eg, CRP)

Thrombogenic hemostatic factors

Impaired fasting glucose

Homocysteine

“Emerging” Risk Factors:Lipid and Non-Lipid
  • Triglycerides
  • Lipoprotein remnants
  • Lipoprotein(a)
  • Small LDL particles
  • HDL subspecies
  • Apolipoproteins
    • Apolipoprotein B
    • Apolipoprotein A1

Keep in mind that 80%-90% of CHD is due to standard risk factors

Khot UN, et al. JAMA. 2003;290:898-904; NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/;Pearson TA, et al. Circulation. 2003;107:499-511.

conclusion practicing clinicians dyslipidemia cases
Conclusion: Practicing Clinicians Dyslipidemia Cases
  • Since NCEP ATP III, there have been a number of major clinical trials of statins with end points highly relevant to clinical practice
  • Based on these trials, NCEP ATP III now recommends optional LDL-C goals of:
    • <70 mg/dL for patients at very high risk
    • <100 mg/dL for patients at moderately high risk
  • Further, NCEP ATP III now advises that lipid-lowering therapy should result in at least a 30% to 40% reduction in LDL-C in moderate- or high-risk patients
  • CK levels must rise >10-fold (>1500 mg/dL) for risk of stopping statin therapy to outweigh benefit
  • Assessment of emerging risk factors is optional but may be valuable in selected cases
slide99

No Diabetes

Diabetes

Age-Adjusted Prevalence of Heart Disease and Stroke Among Adults Aged 35 Years With and Without Diabetes: US, 1999-2001

40

35

30

25

Prevalence (%)

20

15

10

5

0

Coronary Heart

Stroke

Other Heart

Disease

Conditions

CDC. MMWR. 2003;52:1065-1070.

established modifiable cv risk factors in type 2 diabetes
Established Modifiable CV Risk Factors in Type 2 Diabetes

UKPDS 23

Adjusted for age and sex in 2693 white patients with type 2 DM with dependent variable as time to first event.

*Significant for CAD (n = 280). P values are significance of risk factors after controlling for all other risk factors in model.

Turner RC, et al. BMJ. 1998;316:823-828.

cv risk factor control among adults with diagnosed diabetes

48.2

44.3

37.0

35.8

33.9

29.0

7.3

5.2

CV Risk Factor Control Among Adults With Diagnosed Diabetes

Fewer than half of adults with diabetes achieve treatment goals for CV risk factors

NHANES III (n = 1204)

60

NHANES 1999-2000 (n = 370)

50

40

Adults (%)

30

20

10

0

Blood Pressure

<130/80 mm Hg

Total Cholesterol*

<200 mg/dL

Achieved all 3 treatment goals

A1CLevel<7%

*LDL-C and TG not evaluated.

Saydah SH, et al. JAMA. 2004;291:335-342.

practicing clinicians case study 5 62 year old hispanic woman with pvd and hypertension
Practicing Clinicians Case Study 5: 62-Year-Old Hispanic Woman With PVD and Hypertension
  • Medications
    • Valsartan 160 mg/d
    • Hydrochlorothiazide 25 mg/d
    • Clopidogrel 75 mg/d
  • Physical examination
    • BP: 136/78 mm Hg
    • Height 5'4"; weight 159 lb; BMI 27.3 kg/m2
    • 1+ peripheral pulses
  • Laboratory values
    • Fasting plasma glucose 116 mg/dL
    • Potassium 5.1 mEq/L; BUN 24 mg/dL; creatinine 1.3 mg/dL (GFR: 42 mL/min/1.73 m2)
    • Urinalysis: microalbuminuria (210 μg/mg creatinine)
    • TC 198 mg/dL; LDL 118 mg/dL; HDL 52 mg/dL; TG 142 mg/dL
  • ECG: LVH with repolarization abnormality
practicing clinicians case study 5 decision point

?

Practicing Clinicians Case Study 5: Decision Point
  • Given this patient’s CV risk factor profile, what would you do at this point?

1. Switch from a thiazide to spironolactone

2. Order an oral glucose tolerance test

3. Switch from an ARB to an ACEI

4. Order advanced lipid testing

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practicing clinicians case study 5 cv risk management pearls testing for diabetes in adults
Practicing Clinicians Case Study 5 CV Risk Management Pearls: Testing for Diabetes in Adults
  • Consider for all patients age ≥45 years, especially if BMI >25 kg/m2
  • Consider at a younger age or carry out more frequently in overweight patients (BMI >25 kg/m2) and have additional risk factors, such as:
    • Habitually physically inactive
    • First-degree relative with diabetes
    • Member of a high-risk ethnic population (eg, African American, Latino, Native American, Asian American, Pacific Islander)
    • Hypertensive (140/90 mm Hg)
    • HDL-C level <35 mg/dL and/or a TG level >250 mg/dL
    • IGT or IFG on previous testing
    • Other clinical conditions associated with insulin resistance
    • History of vascular disease

ADA. Diabetes Care. 2004;27(suppl 1):S15-35.

natural history of type 2 diabetes

Insulin resistance

“Metabolic Syndrome”

Insulin secretion

Impaired fasting

glucose

Post-meal glucose

Cardiovascular complications

Microvascular complications

Fasting glucose

Natural History of Type 2 Diabetes

0

10

5

15

-10

-5

Years from

diagnosis

Onset

Diagnosis

Pre-diabetes

Type 2 diabetes

Nathan DM. N Engl J Med. 2002;347:1342-1349; Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789.

practicing clinicians case study 5 decision point106

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Practicing Clinicians Case Study 5: Decision Point
  • The patient’s 2-h plasma glucose is 206 mg/dL (first test) and 212 mg/dL (second test), and you diagnose diabetes. In addition to glucose management, what would you do now?

1. Establish BP control, then treat LDL-C to <100 mg/dL

2. Treat LDL-C to <70 mg/dL, then establish BP control

3. Address BP and LDL-C abnormalities simultaneously

4. Perform comprehensive quantitative CV risk assessment prior to additional therapy

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hps major vascular events by ldl c and prior diabetes
HPS: Major Vascular Eventsby LDL-C and Prior Diabetes

Rate ratio (95% CI)

Statin better

Placebo better

0.76 (0.72-0.81) P <.0001

0.4

0.6

0.8

1.0

1.2

1.4

HPS Collaborative Group. Lancet. 2003;361:2005-2016.

cards trial clinical question
CARDS Trial: Clinical Question
  • Is atorvastatin 10 mg/d, when compared with placebo, beneficial for primary prevention of major CV events in patients with type 2 diabetes who do not have high levels of LDL-C?

CARDS = Collaborative Atorvastatin Diabetes Study.

Colhoun HM, et al. Lancet. 2004;364:685-696.

cards primary end point major cardiovascular events
CARDS Primary End Point: Major Cardiovascular Events

15

Placebo No. of events: 127

Atorvastatin No. of events: 83

37%

10

N = 2838

Cumulative Hazard (%)

5

RRR 37% (95% CI, 17%-52%)

P = .001

0

0

1

2

3

4

4.75

Years

RRR = relative risk reduction.

Colhoun HM, et al. Lancet. 2004;364:685-696.

ukpds tight glucose versus tight bp control and cv outcomes
UKPDS: Tight Glucose Versus Tight BP Control and CV Outcomes

Tight glucose control

(goal <6.0 mmol/L or 108 mg/dL)

Tight BP control

(average 144/82 mm Hg)

Stroke

Any Diabetic

End Point

DM

Deaths

Microvascular

Complications

0

5%

-10

10%

12%

-20

Relative Risk Reduction (%)

24%

-30

*

32%

32%

*

37%

-40

*

44%

*P <.05 compared to tight glucose control

*

-50

UKPDS = United Kingdom Prospective Diabetes Study.

Bakris GL, et al. Am J Kidney Dis. 2000;36:646-661.

steno 2 interventions for intensive treatment group
Steno-2: Interventions for Intensive Treatment Group
  • Low-fat diet
  • Exercise
  • Smoking cessation
  • ACE inhibitor or ARB
  • Multivitamin
  • Aspirin
  • A1C goal <6.5%
  • Initial blood pressure goal <140/85 mm Hg (goals revised during study)
  • Atorvastatin or equivalent statin and/or fibrate

Gaede P, et al. N Engl J Med. 2003;348:383-393.

steno 2 study kaplan meier estimates of composite end point
Steno-2 Study: Kaplan-Meier Estimates of Composite End Point

60

P = .007

50

Conventional therapy

40

Primary Composite End Point (%)

30

20

Intensive therapy

10

0

0

12

24

36

48

60

72

84

96

Follow-up (months)

Gaede P, et al. N Engl J Med. 2003;348:383-393.

proactive primary end point
PROACTIVE Primary End Point*

Placebo No. of events: 572

Pioglitazone No. of events: 514

25

20

N = 5238

15

Proportion of Events (%)

10

HR = 0.90 (95% CI, 0.80-1.02)

P = .095

5

0

6

12

18

24

0

30

36

Time From Randomization (months)

*Death from any cause, nonfatal MI (including silent MI), stroke, ACS, leg amputation, coronary revascularization, or revascularization of the leg.

PROACTIVE = PROspective pioglitAzone Clinical Trial In macroVascular Events.

Dormandy JA, et al. Lancet. 2005;366:1279-1289.

proactive secondary end point
PROACTIVE Secondary End Point*

Placebo No. of events: 358

Pioglitazone No. of events: 301

25

20

N = 5238

15

Proportion of Events (%)

10

HR = 0.84 (95% CI, 0.72-0.98)

P = .027

5

0

6

12

18

24

0

30

36

Time From Randomization (months)

*Death from any cause, nonfatal MI (excluding silent MI), or stroke.

Dormandy JA, et al. Lancet. 2005;366:1279-1289.

slide115
Practicing Clinicians Case Study 6: 50-Year-Old White Man With HTN and Family History of Premature CAD
  • 50-year-old white man with family history of premature CAD (father had MI at age 52)
  • Presents for evaluation and recommendations
  • PMH
    • HTN for 5 yrs; treated with ARB
    • No known CAD, DM, or thyroid disease
  • Height: 5' 10", weight 211 lbs, waist 39"
  • Blood pressure: 148/94 mm Hg
  • 24 pack-year history smoking
  • No regular exercise program
practicing clinicians case study 6 additional data
Practicing Clinicians Case Study 6: Additional Data
  • Stressful job as manager in an investment firm
  • Often “eats on the run”
  • Laboratory studies reveal:
    • Lipids:
      • TG 484 mg/dL
      • TC 272 mg/dL
      • HDL 35 mg/dL
      • LDL 140 mg/dL
    • Fasting glucose 158 mg/dL
    • Renal, hepatic, and thyroid function WNL
  • ECG unremarkable
practicing clinicians case study 6 decision point

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Practicing Clinicians Case Study 6: Decision Point
  • Which of the following findings suggestthat this patient may have the metabolic syndrome?

1. TG 484 mg/dL, HDL 35 mg/dL, fasting glucose 158 mg/dL

2. TG 484 mg/dL, HDL 35 mg/dL, LDL 140 mg/dL

3. Family history premature CAD, smoking history, TC 272 mg/dL

4. Absence of thyroid disease, BP 148/94 mm Hg, TC 272 mg/dL

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definition of the metabolic syndrome 2005 update
Definition of the Metabolic Syndrome: 2005 Update

*Presence of 3 or more of these factors identifies the metabolic syndrome.

†A lower threshold can be used for patients especially prone to insulin resistance, particularly Asian Americans.

Grundy SM, et al. Circulation. 2005;112:2735-2752.

NOTE: The ADA recently issued a statement calling for a critical appraisal of the metabolic syndrome. Kahn R, et al. Diabetologia. 2005;48:1684-1699.

management of the metabolic syndrome 2005 update
Management of the Metabolic Syndrome: 2005 Update
  • Weight reduction
  • Increased physical activity
  • Modification of atherogenic diet
  • Drug therapy for dyslipidemia
  • Drug therapy for hypertension
  • Aspirin or clopidogrel for prothrombotic state
  • Lifestyle changes to lower serum glucose (if diabetes has developed, drug therapy may also be needed to reduce A1C to ADA goal of <7%)

Grundy SM, et al. Circulation. 2005;112:2735-2752.

association of mi and stroke with the metabolic syndrome
Association of MI and Stroke With the Metabolic Syndrome
  • Analyzed 10,357 subjects from NHANES III
  • Applied NCEP ATP III criteria for the metabolic syndrome
  • Determined relationship of the metabolic syndrome to MI and stroke

3.0

2.16†

2.01*

2.0

Odds Ratio

1.0

0

Stroke

MI

*P <.0001

†P <.0002

Ninomiya JK, et al. Circulation. 2004;109:42-46.

practicing clinicians case study 6 decision point121

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Practicing Clinicians Case Study 6: Decision Point
  • The patient proves to have diabetes, on top of being a smoker, having HTN, and having the metabolic syndrome. A1C is 7.8%. What would you prescribe at this point for lipid management?

1. Fenofibrate

2. Fenofibrate and a statin

3. Extended-release niacin and a statin

4. Intensive statin therapy

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non hdl c as a secondary target
Non-HDL-C as a Secondary Target

Triglyceride levels 200-499 mg/dL identify non-HDL-C as a secondary target of therapy. Goals for non-HDL-C are 30 mg/dL higher than those for LDL-C.

Non-HDL-C = TC – HDL-C = LDL-C + VLDL.

NCEP ATP III. 2002. NIH Publication No. 02-5215.

Grundy SM, et al. Circulation. 2004;110:227-239; NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/.

practicing clinicians case study 6 initial management plan
Practicing Clinicians Case Study 6: Initial Management Plan
  • Lifestyle management
    • Diet, exercise, and smoking cessation
  • Fenofibrate 145 mg/d
  • Simvastatin 20 mg/d
  • Metformin 500 mg bid
  • ASA 81 mg/d
  • Fish oil 1 g bid
treatment of hypertriglyceridemia with fibrates
Agents

Gemfibrozil

Fenofibrate

Effects on Lipids

Increase/decrease LDL

Decrease TGs

Increase HDL

Treatment of HypertriglyceridemiaWith Fibrates
  • Mechanism of Action
    • Decreased hepatic secretion of VLDL
    • Decreased release of FFA from adipose tissue
    • PPAR activation
      • Nuclear hormone receptor gene superfamily
      • Function as a transcription activator/suppressor for genes involved in lipoprotein metabolism

FFA = free fatty acids; PPAR = peroxisome proliferator-activated receptor.

field primary outcome
FIELD: Primary Outcome

FIELD = Fenofibrate Intervention and Event Lowering in Diabetes.

FIELD Study Investigators. Lancet. 2005;366:1849-1861.

va hit study effect of gemfibrozil on chd death nonfatal mi or stroke
VA-HIT Study: Effect of Gemfibrozil on CHD Death, Nonfatal MI, or Stroke

24%RR (95% CI, -0.1%-43%) P = .05

Placebo

Gemfibrozil

45

40

35

30

25

20

15

10

5

0

36

24%RR (95% CI, 6%-30%) P = .009

28

23

Event Incidence (%)

18

Nondiabetic Patients

n = 1904

Diabetic Patients

n = 627

VA-HIT = Veterans Affairs Cooperative Studies Program High-Density Lipoprotein

Cholesterol Intervention Trial

Rubins HB, et al. N Engl J Med. 1999;341:410–418.

combination therapy in cv risk management
Combination Therapy in CV Risk Management
  • Frequently necessary, especially with more aggressive 2004 NCEP Update goals
  • Need to answer 3 specific questions when making decisions for combination treatment
    • Safety
    • Efficacy
    • Cost
  • Limitations of fixed-dose combination therapy include potential difficulty in titration and determining the cause of adverse effects
predictors of adherence with concomitant antihypertensive and lipid lowering medications
Predictors of Adherence With Concomitant Antihypertensive and Lipid-Lowering Medications

Therapy Initiation*

Demographics*

Start AHT/LLT(0-30 d)

1.34 (P <.001)

1.00 (ref group)

Age (18-44)

Age (55-64)

Start AHT/LLT(31-60 d)

1.56 (P <.001)

1.09 (P = .25)

1.27 (P = .004)

Age (65-74)

Start AHT/LLT(61-90 d)

1.00 (ref group)

No. of Concomitant Meds*

Sex (female)

0.91 (P = .02)

0

1.96 (P <.001)

No CAD

1.00 (ref group)

1

1.61 (P <.001)

CAD Level 1 (angina or coronary angiography)

0.96 (P = .73)

2

1.30 (P <.001)

3-5

CAD Level 2 (PTCA,

CABG, or chronic CHD)

1.23 (P <.001)

1.20 (P = .001)

³ 6

1.00 (ref group)

1.28 (P = .003)

CAD Level 3 (acute MI)

0.5

1

2.0

2.5

0.5

1

2.0

2.5

Nonadherent

Adherent

Adherent

Nonadherent

*Odds ratio (95% CI).

AHT = antihypertensive therapy; LLT = lipid-lowering therapy.

Chapman RH, et al. Arch Intern Med. 2005;165:1147-1152.

adherence to simultaneous antihypertensive and lipid regulating drug therapy
Adherence to Simultaneous Antihypertensive and Lipid-Regulating Drug Therapy

38%

40 −

35 −

27%

30 −

23%

25 −

Patients Adhering to Therapy (%)

20 −

15 −

10 −

5 −

0 −

AHD First, LRD Added

LRD First, AHD Added

AHD + LRD Initiated

Simultaneously

AHD = antihypertensive drug; LRD = lipid-regulating drug.

Adapted from Schwartz JS, et al. ACC 2003. Poster.

adherence to antihypertensive therapy with combination pill
Adherence to Antihypertensive Therapy With Combination Pill

P <.001

80.8

81

80

79

78

77

Overall Medication Possession Ratio (%)

76

73.8

75

74

73

72

71

70

0

ACE Inhibitor/ DCCB Concurrently

Amlodipine/ Benazepril Combination

DCCB = dihydropyridine calcium channel blocker.

Taylor AA, Shoheiber O. Congest Heart Fail. 2003;9:324-332.

adherence decreases in patients switched to separate oral antidiabetic agents

82

54

Monotherapy

(n = 33,567)

Switched to

Gly + Met

(n = 1815)

Adherence Decreases in Patients Switched to Separate Oral Antidiabetic Agents

100

77

80

60

Adherence (%)

40

20

0

Switched to

Gly/Met

(n = 105)

Adherence = days supplied/total days.

Melikian C, et al. Clin Ther. 2002;24:460-467.

combination drugs for treatment of diabetes dyslipidemia and hypertension
Combination Drugs for Treatment of Diabetes, Dyslipidemia, and Hypertension

*Established combinations of diuretics and antihypertensive agents too numerous to list.

Adapted from Leichter SB, Thomas S. Clin Diab. 2003;21:175-178.

conclusion diabetes cases
Conclusion: Diabetes Cases
  • As of NHANES 1999-2000, only ~ 7% of patients with diabetes were achieving all 3 of the followingCV risk management goals:
    • A1C <7%
    • BP <130/80 mm Hg
    • TC <200 mg/dL (LDL-C and TG not evaluated)
  • CV risk management in patients with diabetes is an important process requiring a full arsenal of clinical information, especially renal and cardiac function
  • Adherence in patients with multiple CV risk factors may be significantly improved with combination therapy
  • Remember the importance of total CV risk management
a reminder and thanks
A Reminder–and Thanks
  • Please be sure to complete your CME/CE evaluation form and give it to a representative of CE Alliance as you leave
  • Thanks for coming!
a cv risk education symposium

A CV Risk Education Symposium

Integrating Total CV Risk Management Into Clinical Practice