Case Study: A 52YearOld Woman With HTN and DM Who Presents With Chest Pain

1
Case Study A 52-Year-Old Woman With HTN and DM
Who Presents With Chest Pain

• ? ? ? ? ?
• ???????????
• George D. Harris, MD, MS .
• Clinical Diabetes115-118, 2007.
• 96-08-31 ? ????

2
Presentation (1)

• L.R. 52-year-old Caucasian woman ,history of
  pre-HTN, dyslipidemia, and type 2 DM. She
  presented to the office 6 months ago. She had no
  complaints except for some occasional fatigue.
• She smoked cigarettes as a teenager and young
  adult but quit 25 years ago.
• FH HTN, type 2 DM, and MI (father at age 62 and
  mother at age 68).
• PE a healthy appearing woman with height of
  5'4'' and weight of 168 lb (BMI of 28.8 kg/m2).
  BP 138/88 mmHg.
• Lab random glucose 180 mg/dl, TG 185 mg/dl, Chol
  225 mg/dl, HDL 52 mg/dl, LDL 132 mg/dl, and A1C
  7.6.
• Tx a sulfonylurea and metformin twice daily for
  her DM and atorvastatin daily for her
  dyslipidemia.

3
Presentation (2)

• She was instructed about starting a daily
  exercise program and agreed to a weight loss
  program.
• She seemed to be doing well until she presented
  to the ER complaining of SOB and palpitations.
• On admission, she had elevated BP in the range of
  138-146 mmHg systolic and 86-90 mmHg diastolic.
• Her evaluation was negative, with normal EKG and
  cardiac enzymes. She was discharged the next
  morning on her same DM and cholesterol
  medications.
• A diuretic was added for her BP. She was asked to
  follow up in the office in 1 week.

4
Presentation (3)

• At the 1-week follow-up visit, BW 175 lb (BMI
  30.0 kg/m2) and BP 132/86 mmHg. She admitted to
  not exercising and not being serious about her
  weight loss program.
• Her 10-year coronary heart disease risk 11, with
  an average risk for her age of 8 (low risk for
  her age would be 5), giving her a relative risk
  of 2.2.
• She was referred for a medical nutrition therapy
  consultation for dietary modification.
• She promised to start a brisk walking(???)
  program each evening for 30 minutes. She was
  scheduled for an exercise treadmill test and
  asked to follow-up in 6 weeks.

5
Questions

• What are the present American Heart Association
  (AHA) recommendations for this p't now?
• Where are the recommendations according to the
  Framingham Global Risk Model?
• What tests should now be ordered?
• What medications or supplements are recommended
  and not recommended for primary or secondary
  prevention of CVD?

6
Commentary (1)

• In USA, gt 9 million women gt 20 Y/O have type 1 or
  type 2 DM, with 90-95 of all diagnosed cases
  having type 2 DM.
• CVD is the largest single cause of death among
  women worldwide. In USA, more women than men die
  of CVD annually.
• 36 of women do not perceive(??) themselves to be
  at risk, and this has underscored(??) the need
  for a special area of focus on CVD and its
  prevention in women.
• Chest pain is the most common presenting symptom
  of MI in both men and women, but women are less
  likely to present with typical anginal symptoms.
• In a study of 515 women with acute MI, chest pain
  was absent in 43 of the p'ts, and when the women
  did experience chest pain, it was described as
  pressure (21.9), ache (15), or tightness
  (14).(Circulation108 2619-2623,2003 )

7
Women's early warning symptoms of AMI

• BACKGROUND Data remain sparse on women's
  prodromal symptoms before AMI. This study
  describes prodromal and AMI symptoms in women.
• METHODS AND RESULTS Participants were 515 women
  diagnosed with AMI from 5 sites. Using the
  McSweeney Acute and Prodromal MI Symptom Survey,
  we surveyed them 4 to 6 months after discharge,
  asking about symptoms, comorbidities, and
  demographic characteristics. Women were
  predominantly white (93), high school educated
  (54.8), and older (mean age, 66/-12), with 95
  (n489) reporting prodromal symptoms. The most
  frequent prodromal symptoms experienced more than
  1 month before AMI were unusual fatigue (70.7),
  sleep disturbance (47.8), and SOB (42.1). Only
  29.7 reported chest discomfort, a hallmark
  symptom in men.

Circulation108 2619-2623,2003.
8

• The most frequent acute symptoms were SOB
  (57.9), weakness (54.8), and fatigue (42.9).
  Acute chest pain was absent in 43. Women had
  more acute (mean, 7.3/-4.8 range, 0 to 29) than
  prodromal (mean, 5.71/-4.36 range, 0 to 25)
  symptoms. The average prodromal score, symptom
  weighted by frequency and intensity, was
  58.5/-52.7, whereas the average acute score,
  symptom weighted by intensity, was 16.5/-12.1.
  These 2 scores were correlated (r0.61, Plt0.001).
  Women with more prodromal symptoms experienced
  more acute symptoms. After controlling for risk
  factors, prodromal scores accounted for 33.2 of
  acute symptomatology.
• CONCLUSIONS Most women have prodromal symptoms
  before AMI. It remains unknown whether prodromal
  symptoms are predictive of future events.

Circulation108 2619-2623,2003.
9
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10
Commentary (2)

• Women with atypical symptoms (e.g., back pain,
  nausea, indigestion, dyspnea, or fatigue)often
  ignored and delayed presentation diagnosis.
• Recent AHA guidelines urge women to start an
  early healthy lifestyle with new target goals for
  risk assessment.
• DM adult women have heart disease present at two
  to four times higher rates than those without DM.
  The focus is on prevention.
• Initial CVD risk evaluation (history, P.E., and
  FPG and lipid testing) and Framingham risk
  assessment are recommended in all women gt 20 Y/O.
  
• Mosca et al. a new Framingham Global Risk Model
  -- three categories (high risk, at risk, and
  optimal risk), instead of the previous four
  categories (high, intermediate, lower, and
  optimal), decreasing the limitations of the
  previous risk model and allowing for
  determination of a women's lifetime risk,
  diversity, and stroke risk (Figure 1).

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(Figure 1).
12
(No Transcript)
13
Commentary (3)

• Exercise testing in DM is given a IIb
  classification by the AHA and the American
  College of Cardiology. This classification states
  that "usefulness or efficacy is less well
  established by evidence or opinion."
• Exercise treadmill testing in general "might be
  useful in people with heightened pretest risk."
• Criteria for high risk CAD, cerebral vascular
  disease, PAOD, abdominal aortic aneurysm,
  end-stage or chronic renal disease, and DM and
  provide a global risk score of gt 20.
• An estimated 10-year risk gt 20 may require
  aggressive interventions.

14
Commentary (4)

• At-risk individuals have one or more of the
  following major CVD risk factors smoking, poor
  diet, physical inactivity, obesity, F.H. of
  premature CVD, HTN, dyslipidemia, metabolic
  syndrome, and poor exercise capacity on treadmill
  testing.
• Other tests to consider include high-sensitivity
  CRP, electron-beam CT (a new test that can be
  used to find calcium buildup in the lining of
  coronary arteries) , measurement of
  ankle-brachial index, and ultrasound to measure
  carotid intima-media thickness.

15
Commentary (5)

• CRP is a stronger predictor of CV events than LDL
  level and that it adds prognostic information to
  that conveyed by the Framingham risk score.
• Criteria for optimal risk (global risk score lt
  10) a healthy lifestyle that should indicate
  conservative management focusing on maintaining
  appropriate lifestyle interventions.
• Lifestyle recommendations smoking cessation, a
  heart-healthy diet (rich in vegetables, whole
  grains, and oily fish), daily exercise, and
  weight management are indicated for all women gt
  20 Y/O (AHA evidence Class I).

16
Commentary (6)

• DM should be encouraged to perform 30-60 minutes
  of moderate-intensity aerobic activity, such as
  brisk walking, on most (preferably all) days of
  the week.
• Lifestyle and pharmacotherapy indicated in women
  with DM (AHA evidence Class I Level B) to achieve
  an A1C lt 7 if this can be accomplished without
  significant hypoglycemia (AHA evidence Class I
  Level C).
• For women gt 65 Y/O, 81 mg of aspirin daily is
  recommended if BP is controlled.
• Clopidogrel (Plavix) for individuals who cannot
  take aspirin.
• In addition, all high-risk women need BP control
  (AHA evidence Class I) and to take an aspirin
  each day (AHA evidence Class Ia) or clopidogrel
  (AHA evidence Class Ib).

17
Commentary (7)

• Before initiating a vigorous exercise program,
  individuals with DM should be assessed for
  conditions that might contraindicate certain
  types of exercise or predispose to injury.
• No randomized trials or large cohort studies have
  evaluated the utility of exercise stress testing
  specifically in DM, the decision to perform
  stress testing for p'ts beginning a vigorous
  exercise program must be made on an individual
  basis.
• Low exercise capacity may be an independent
  predictor of death in women. (Circulation
  1081554 -1559, 2003 )
• Interpreting the level of exercise achieved with
  regard to age-predicted values of exercise
  capacity in women may provide additional
  prognostic information for risk stratification.
  (N Engl J Med 353 468-475,2005)

18
Exercise capacity and the risk of death in women
the St James Women Take Heart Project.

• BACKGROUND CVD is the leading cause of death
  among women and accounts for more than half of
  their deaths. Women have been underrepresented in
  most studies of CVD. Reduced physical fitness has
  been shown to increase the risk of death in men.
  Exercise capacity measured by exercise stress
  test is an objective measure of physical fitness.
  The hypothesis that reduced exercise capacity is
  associated with an increased risk of death was
  investigated in a cohort of 5721 asymptomatic
  women who underwent baseline examinations in
  1992.

Circulation 1081554 -1559, 2003
19

• METHODS AND RESULTS Information collected at
  baseline included medical and family history,
  demographic characteristics, physical
  examination, and symptom-limited stress ECG,
  using the Bruce protocol. Exercise capacity was
  measured in metabolic equivalents (MET).
  Nonfasting blood was analyzed at baseline. A
  National Death Index search was performed to
  identify all-cause death and date of death up to
  the end of 2000. The mean age of participants at
  baseline was 52/-11 years. Framingham Risk
  Score-adjusted hazards ratios (with 95 CI) of
  death associated with MET levels of lt5, 5 to 8,
  and gt8 were 3.1 (2.0 to 4.7), 1.9 (1.3 to 2.9),
  and 1.00, respectively. The Framingham Risk
  Score-adjusted mortality risk decreased by 17
  for every 1-MET increase.
• CONCLUSIONS This is the largest cohort of
  asymptomatic women studied in this context over
  the longest period of follow-up. This study
  confirms that exercise capacity is an independent
  predictor of death in asymptomatic women, greater
  than what has been previously established among
  men. The implications for clinical practice and
  health care policy are far reaching.

Circulation 1081554 -1559, 2003
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The Prognostic Value of a Nomogram for Exercise
Capacity in Women

• Background Recent studies have demonstrated that
  exercise capacity is an independent predictor of
  mortality in women. Normative values of exercise
  capacity for age in women have not been well
  established. Our objectives were to construct a
  nomogram to permit determination of predicted
  exercise capacity for age in women and to assess
  the predictive value of the nomogram with respect
  to survival.
• Methods A total of 5721 asymptomatic women
  underwent a symptom-limited, maximal stress test.
  Exercise capacity was measured in metabolic
  equivalents (MET). Linear regression was used to
  estimate the mean MET achieved for age. A
  nomogram was established to allow the percentage
  of predicted exercise capacity to be estimated on
  the basis of age and the exercise capacity
  achieved. The nomogram was then used to determine
  the percentage of predicted exercise capacity for
  both the original cohort and a referral
  population of 4471 women with CV symptoms who
  underwent a symptom-limited stress test. Survival
  data were obtained for both cohorts, and Cox
  survival analysis was used to estimate the rates
  of death from any cause and from cardiac causes
  in each group.

N Engl J Med353 468-475,2005
21

• Results The linear regression equation for
  predicted exercise capacity (in MET) on the basis
  of age in the cohort of asymptomatic women was as
  follows predicted MET 14.7 (0.13 x age). The
  risk of death among asymptomatic women whose
  exercise capacity was less than 85 percent of the
  predicted value for age was twice that among
  women whose exercise capacity was at least 85
  percent of the age-predicted value (Plt0.001).
  Results were similar in the cohort of symptomatic
  women.
• Conclusions We have established a nomogram for
  predicted exercise capacity on the basis of age
  that is predictive of survival among both
  asymptomatic and symptomatic women. These
  findings could be incorporated into the
  interpretation of exercise stress tests,
  providing additional prognostic information for
  risk stratification.

N Engl J Med353 468-475,2005
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Commentary (8)

• AHA clarifies how to use aspirin, vitamins, and
  supplements to prevent heart disease in women.
• Women should not receive hormone therapy or
  estrogen modulators, antioxidant vitamin
  supplements (vitamins A, E, C, and
  beta-carotene), or folic acid or use aspirin
  routinely (in healthy women lt 65 Y/O) for primary
  or secondary prevention.
• Vitamin A, beta-carotene, and high-dose vitamin E
  may increase CV mortality. Although high-dose
  folic acid may decrease homocysteine levels, it
  is not recommended to prevent heart disease.
• There is good evidence supporting the use of
  omega-3 fatty acids, which should be taken daily
  (1 g/day).

23
Commentary (9)

• Major risk factor interventions include achieving
  an optimal BP of lt 120/80 mmHg, LDL lt 100 mg/dl
  (except for those at high risk, who should
  achieve an LDL lt 70 mg/dl), HDL gt 50 mg/dl, TG lt
  150 mg/dl, and A1C levels lt 7 or as close to
  normal (lt 6) as possible without causing
  significant hypoglycemia if DM is present.
• These recommendations are based on
  epidemiological studies each 1 increase in A1C
  is associated with a 15 and 18 increase in the
  relative risk of CVD for type 1 and type 2 DM,
  respectively.(Ann Intern Med 141421 -431, 2004)

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Meta-Analysis A1c and CVD in DM

• Background In persons with DM, chronic
  hyperglycemia (assessed by A1c level) is related
  to the development of microvascular disease
  however, the relation of A1c to macrovascular
  disease is less clear.
• Purpose To conduct a meta-analysis of
  observational studies of the association between
  A1c and CVD in diabetic persons.
• Data Sources Search of the MEDLINE database by
  using Medical Subject Heading search terms and
  key words related to A1c, DM, and CVD.
• Study Selection Prospective cohort studies with
  data on A1c levels and incident CVD.
• Data Extraction Relative risk estimates were
  derived or abstracted from each cohort study that
  met the inclusion criteria.

Ann Intern Med 141421 -431, 2004
25

• Data Synthesis Adjusted relative risk estimates
  for A1c (total A1c, hemoglobin A1, or hemoglobin
  A1c levels) and CVD events (coronary heart
  disease and stroke) were pooled by using
  random-effects models. Three studies involved
  persons with type 1 DM (n 1688), and 10 studies
  involved persons with type 2 DM (n 7435). The
  pooled relative risk for CVD was 1.18 this
  represented a 1percentage point increase in A1c
  level (95 CI, 1.10 to 1.26) in persons with type
  2 DM. Results in persons with type 1 DM were
  similar but had a wider CI (pooled relative risk,
  1.15 CI, 0.92 to 1.43).
• Limitations This review largely reflects the
  limitations of the literature. Important concerns
  were residual confounding, the possibility of
  publication bias, the small number of studies,
  and the heterogeneity of study results.
• Conclusions Pending confirmation from large,
  ongoing clinical trials, this analysis shows that
  observational studies are consistent with limited
  clinical trial data and suggests that chronic
  hyperglycemia is associated with an increased
  risk for CVD in persons with DM.

Ann Intern Med 141421 -431, 2004
26
Commentary (10)

• The National Heart, Lung, and Blood Institute ATP
  III designated DM as a CVD risk equivalent for
  setting treatment goals for LDL. (Circulation110
  227-239,2004 )
• Type 2 DM places individuals at increased risk of
  an MI within a 10-year period. (P'ts with DM are
  at high risk for future CVD events, and their
  absolute risk for future events is very high.)
  Even in the absence of CVD, both the ADA and AHA
  identify DM as a high-risk condition for
  macrovascular CVD.
• In p'ts with type 2 DM and other risk factors,
  statin therapy reduce CV risk (22-24 relative
  risk reduction in both primary and secondary CV
  prevention studies). (Ann Intern Med 140650
  -658, 2004.)
• The ADA recommends that individuals gt 40 Y/O with
  type 2 DM should be treated with a statin in
  doses high enough to lower LDL by 30-40,
  regardless of baseline LDL.
• LDL-lowering drugs should be used simultaneously
  with lifestyle therapy in women with coronary
  heart disease to achieve an LDL lt 100 mg/dl (AHA
  evidence Class I Level A) and similarly in women
  with other atherosclerotic CVD or DM or 10-year
  absolute risk gt 20 (AHA evidence Class I Level
  B).
• A reduction to lt 70 mg/dl is reasonable in
  very-high-risk women with coronary heart disease
  and may require an LDL-lowering drug combination
  (AHA evidence Class IIa Level B).

27
Implications of recent clinical trials for the
National Cholesterol Education Program Adult
Treatment Panel III guidelines.

• The ATP III of the NCEP issued an evidence-based
  set of guidelines on cholesterol management in
  2001.
• Since the publication of ATP III, 5 major
  clinical trials of statin therapy with clinical
  end points have been published. These trials
  addressed issues that were not examined in
  previous clinical trials of cholesterol-lowering
  therapy.
• The present document reviews the results of these
  recent trials and assesses their implications for
  cholesterol management.
• Therapeutic lifestyle changes (TLC) remain an
  essential modality in clinical management. The
  trials confirm the benefit of cholesterol-lowering
  therapy in high-risk p'ts and support the ATP
  III treatment goal of LDL-C lt100 mg/dL.

Circulation110 227-239,2004
28

• They support the inclusion of p'ts with DM in the
  high-risk category and confirm the benefits of
  LDL-lowering therapy in these p'ts. They further
  confirm that older persons benefit from
  therapeutic lowering of LDL-C. The major
  recommendations for modifications to footnote the
  ATP III treatment algorithm are the following.
• In high-risk persons, the recommended LDL-C goal
  is lt100 mg/dL, but when risk is very high, an
  LDL-C goal of lt70 mg/dL is a therapeutic option,
  ie, a reasonable clinical strategy, on the basis
  of available clinical trial evidence.
• This therapeutic option extends also to p'ts at
  very high risk who have a baseline LDL-C lt100
  mg/dL. Moreover, when a high-risk p't has high TG
  or low HDL-C, consideration can be given to
  combining a fibrate or nicotinic acid with an
  LDL-lowering drug.
• For moderately high-risk persons (2 risk factors
  and 10-year risk 10 to 20), the recommended
  LDL-C goal is lt130 mg/dL, but an LDL-C goal lt100
  mg/dL is a therapeutic option on the basis of
  recent trial evidence. The latter option extends
  also to moderately high-risk persons with a
  baseline LDL-C of 100 to 129 mg/dL.

Circulation110 227-239,2004
29

• When LDL-lowering drug therapy is employed in
  high-risk or moderately high-risk persons, it is
  advised that intensity of therapy be sufficient
  to achieve at least a 30 to 40 reduction in
  LDL-C levels.
• Moreover, any person at high risk or moderately
  high risk who has lifestyle-related risk factors
  (eg, obesity, physical inactivity, elevated TG,
  low HDL-C, or metabolic syndrome) is a candidate
  for TLC to modify these risk factors regardless
  of LDL-C level.
• Finally, for people in lower-risk categories,
  recent clinical trials do not modify the goals
  and cutpoints of therapy.

Circulation110 227-239,2004
30
Pharmacologic Lipid-Lowering Therapy in Type 2
DM Background Paper for the American College of
Physicians

• Background CVD is the primary complication and
  cause of death in p'ts with type 2 DM.
  Modification of CV risk factors may improve p't
  outcomes.
• Purpose To evaluate the effectiveness of
  pharmacologic lipid-lowering therapy on outcomes
  in type 2 DM.
• Data Sources Review of the literature.
• Study Selection Randomized trials evaluating
  clinical outcomes of lipid-lowering treatment in
  p'ts with DM.
• Data Extraction Studies were identified by
  searching the Cochrane Library, MEDLINE,
  meta-analyses, review articles, and inquiries to
  experts. The Cochrane Library and MEDLINE
  searches were done in September 2002. Data were
  abstracted onto standardized forms by a single
  reviewer and were confirmed by a second reviewer.

Ann Intern Med 140650 -658, 2004.
31

• Data Synthesis Meta-analysis of 6 primary
  prevention studies showed that lipid-lowering
  medications reduced risks for CV outcomes
  (relative risk, 0.78 95 CI, 0.67 to 0.89
  absolute risk reduction, 0.03 CI, 0.01 to 0.04
  in 4.3 years of treatment) 1 major CV event was
  prevented by treating 34 to 35 p'ts.
  Meta-analysis of 8 studies of secondary
  prevention showed a similar relative risk (0.76
  CI, 0.59 to 0.93) but more than twice the
  absolute risk reduction (0.07 CI, 0.03 to 0.12
  in 4.9 years of treatment) and a number needed to
  treat for benefit of 13 to 14. Most studies
  compared a lipid-lowering drug with placebo but
  did not evaluate the effect of reaching specific
  cholesterol levels. The benefit of lipid lowering
  with a fixed dose of a statin appeared to be
  similar regardless of starting cholesterol
  levels.
• Limitations Target cholesterol levels and the
  effectiveness of dose titration (or the use of
  multiple agents) have not been rigorously
  examined.
• Conclusions In p'ts with type 2 DM, treatment
  with lipid-lowering agents reduces CV risk. Most
  p'ts, including those whose baseline LDL levels
  are below 2.97 mmol/L (lt115 mg/dL), and possibly
  below 2.59 mmol/L (lt100 mg/dL), benefit from
  statins. Moderate doses of these drugs suffice in
  most p'ts with DM.

Ann Intern Med 140650 -658, 2004.
32
Clinical Pearls (1)

• Women may present with either typical (chest
  pain) or atypical (back pain, nausea,
  indigestion, dyspnea, fatigue) symptoms of an MI.
  
• Initial CVD risk evaluation (history, P.E., and
  FPG and lipid testing) and Framingham risk
  assessment are recommended in all women gt 20 Y/O.
  
• Lifestyle recommendations of smoking cessation,
  heart-healthy diet (rich in vegetables, whole
  grains, and oily fish), daily exercise, and
  weight management are indicated for all women gt
  20 Y/O.

33
Clinical Pearls (2)

• Women should not receive hormone therapy or
  estrogen modulators, antioxidant vitamin
  supplements (vitamins A, E, C, and beta-carotene)
  or folic acid, or use aspirin routinely (in
  healthy women lt 65 Y/O) for primary or secondary
  prevention.
• The ADA recommends that individuals gt 40 Y/O with
  type 2 DM be treated with a statin in doses high
  enough to lower LDL levels by 30-40 regardless
  of baseline LDL.

34
THANK YOU FOR YOUR ATTENTION !