1. In the name of GOD

2. Cardiovascular risk assessment & management
Hassan Aghajani MD.FSCAI
Interventional cardiologist.Endovascularist
Tehran Heart Center.TUMS

3. Back ground
CVD: is a leading cause of mortality in post menopausal women
Gender specific approach
Encourage all physicians to engage in CVD risk assessment & management
Awareness of woman
Appropriate actions
Self monitoring
Heart-friendly lifestyle
‘Heart Age’

4. Cardiovascular Disease: The Leading Cause of Death in US Women in 1995
Heart disease
375
Cerebrovascular disease
96.4
Lung cancer
60.6
COPD*
48.9
Pneumonia/Influenza
45.1
Breast cancer
43.8
Accidents
31.9
Heart disease has been the leading cause of death for the past 50 years (Supercourse)
Diabetes
33.1
Ovarian cancer
9.9 50
100
150
200
250
300
350
400
Deaths (1,000)
*COPD=chronic obstructive pulmonary disease.
Adapted from Anderson RN et al. Monthly Vital Statistics Report. Vol 45(suppl 2):June 12, 1997.

5. Beyond Cholesterol: Predicting Cardiovascular Risk In the 21st Century
Lipids HTN Diabetes
Behavioral
Hemostatic Thrombotic
Inflammatory
Genetic
Slide 2. Beyond cholesterol: predicting cardiovascular risk in the 21st century. Clearly cholesterol is important but we are finding more and more risk factors for CVD (Supercourse)
As we understand more about the biology of atherothrombosis, we need to move beyond standard cholesterol screening if we are to appreciate the promise of preventive early intervention therapies. While hyperlipidemia, hypertension, and diabetes, as well as the behavioral risk factors of smoking and diet, remain major critical modifiable risk factors for vascular disease, we have learned over the years that many hemostatic and thrombotic markers such as lipoprotein(a), D-dimer, and homocysteine, inflammatory markers such as C-reactive protein (CRP), fibrinogen, and interleukin-6, and genetic markers are all part of the evolving understanding of cardiovascular risk.
Keywords: markers, risk factors
Slide type: figure (chart)

6. Continuum of Patients at Risk for a CHD Event
Post MI/Angina
Secondary
Prevention
Other Atherosclerotic Manifestations
Subclinical Atherosclerosis
Primary Prevention
The triangle of CHD risk, shows the relationship of primary and secondary prevention (Supercourse)
Multiple Risk Factors
Low Risk
Courtesy of CD Furberg.

7. Overview The scope of the problem Symptoms Risk factors
Prevention, diagnosis, and treatment
Pearls from the 2014 ACC Heart of Women’s Health course

8. The Scope of the Problem
Coronary Artery Disease (a.k.a. Coronary Heart Disease)
Cardiovascular Disease
CHD: MI, angina, heart failure, coronary death
Cerebrovascular dz – CVA, TIA
PAD – claudication
Aortic disease: atherosclerosis, TAA, AAA

9. The Scope of the Problem
Heart disease is the biggest killer of women
Cardiovascular disease is BY FAR the biggest killer of women
Roughly 401,000 deaths/year from CVD (vs. 386,000 men)
176,255 deaths/year from CAD
Vs 39,520 deaths from breast cancer
Heart Disease and Stroke Statistics Update, AHA

10. The Scope of the Problem
One woman dies every minute from cardiovascular disease in the U.S.!
Heart Disease and Stroke Statistics Update, AHA

11. The Scope of the Problem
CVD accounts for a third of all female deaths
CVD and CAD disproportionately affect African-American and Latina women
CDC data and Heart Disease and Stroke Statistics Update, AHA

12. The Scope of the Problem
Women are roughly 10 yrs older than men when they present, and have more co-morbidities
Young women also develop CAD and have a worse prognosis than men
Women are more likely to wait before presenting to medical attention
Stangl V, et al. Eur Heart J 2008;29:707; Mosca L et al. Circulation 2005;111:499; Wenger NK. Circulation 2004;109:558; Alter DA et al. JACC 2002;39:1909

13. The Scope of the Problem
Women are referred less often for appropriate testing or treatment
Women with MI are more likely to have complications and increased mortality
Fewer women have been included in studies, so there’s less data

14. Awareness is lacking!

15. Awareness is lacking! ~2500 women > 25 y.o. surveyed
Between , awareness among whole study population nearly doubled: 30%56%
Still low in minorities:
Blacks: 36%
Hispanics: 34%
Mosca L, et al. Fifteen-year trends in awareness of heart disease in women. Circulation 2013; 127.

16. Awareness
Mosca L, et al. Fifteen-year trends in awareness of heart disease in women. Circulation 2013; 127.

17. What are the symptoms? Unusual upper body discomfort
Chest pain or discomfort
Shortness of breath
Breaking out in a cold sweat
Unusual or unexplained fatigue (tiredness)
Light-headedness or sudden dizziness
Nausea (feeling sick to the stomach)

18. Symptoms in women with MI
Study of 515 women with MI
Chest pain absent in 43%
Most common symptom:
Dyspnea in 58%
Weakness in 55%
Fatigue in 43%
Prodrome:
Fatigue in 71%
Sleep disturbance (48%), dyspnea (42%)
McSweeney JC, et al. Circulation 2003;108:2619

19. Symptoms in women with MI
Over 1,000,000 men and women in NRMI registry, (481,581 women)
42% of women presented without CP (vs. 31% of men)
Higher in-hospital mortality in women (14.6%) than in men (10.3%)
Younger women without chest pain were at the highest risk
Canto JG et al. JAMA 2012;307:813

20. Symptoms in women with MI
These women who presented without CP were sicker and fared worse:
More had DM
Later presentation
More Killip III/IV
More NSTEMI
Less timely therapies
Less antiplatelet meds, heparin, BB
Canto JG et al. JAMA 2012;307:813

21. Awareness
Mosca L, et al. Fifteen-year trends in awareness of heart disease in women. Circulation 2013; 127.

22. Awareness
Mosca L, et al. Fifteen-year trends in awareness of heart disease in women. Circulation 2013; 127.

23. Symptoms in women with MI
Sudden cardiac death
Higher rates in men
However, a significantly higher percentage of women who have SCD had no prior symptoms! (63% vs. 44%)
Canto JG et al. JAMA 2012;307:813

24. Risk Factors Age over 55 Dyslipidemia: high LDL and/or low HDL
Family hx of premature CAD
First degree male < 55, female <65
Diabetes
Smoking
Hypertension
Peripheral arterial disease

25. Risk factors Menopause Obesity High triglycerides Metabolic syndrome
Sedentary lifestyle
Collagen vascular disease/autoimmune disease
CKD

26. Risk factors Pregnancy-related Pre-eclampsia, eclampsia
Gestational diabetes
Stillbirth
Miscarriages, esp. multiple
Hx of cancer treatments (XRT)
Depression and stress
Hx of trauma or abuse

27. Risk factors for CVD Smoking
One of the most preventable and powerful risk factors
Globally men> woman are smokers
In Europe & USA more equivalence
Aged y : same rate in more than half of world
Vascular dysfunction pro atherogenic factors

28. Hypertension As powerful R.F in woman as in men. Under-diagnosed
Under treated
For every 20/10 increase in BP
Doubling of mortality from CHD & Stroke for woman aged 40-89Y
Prevalance:
30% of adult woman (developed)
53% (low-middle-in come)

29. Detection and effective management at any age Particular attention to
HX of hypertensive pregnancy disorders
Prevalence in postmenopausal more than twice the prevalence in premenopausal women
Even moderate and borderline HTN(<140/90) more endothelial dysfunction and C.V. complications in women than in men..

30. Management: Benefit of treating HTN at least : equivalent to men.
Rate of hypertensive woman: detected/treated and well controlled only 10%

31. Lipids:
In UK and US;
Incidence of total cholesterol >= 6.5 mmol/L is equivalent or greater in woman compared to men aged 50 & older.
Association between
T.C & LDL levels & CHD death is less strong in women than men.
HDL & TG level are better predictor of CV mortality in women

32. Management: Benefit is similar in men & women.
Mainly CHD prevention and not CVD in general
Jupiter Trial: Statin use in a healthy population with elevated hsCRP: 12% reduction in total mortality in high-risk group(in both gender)

33. Primary prevention in high CVD risk women Secondary prevention MHT:
Statin for
Primary prevention in high CVD risk women
Secondary prevention
MHT:
Decrease LDL / LP (a)
Increase HDL

34. Total Cholesterol Distribution: CHD vs Non-CHD Population
Framingham Heart Study—26-Year Follow-up
No CHD
35% of CHD Occurs in People with TC<200 mg/dL
CHD
Slide 3. Total cholesterol distribution: CHD vs non-CHD population
In the Framingham Heart Study, as many as one third of all coronary heart disease (CHD) events occurred in individuals with total cholesterol <200 mg/dL. Considering that the average U.S. cholesterol level is approximately 210 to 220 mg/dL, almost half of all heart attack events and all stroke events that will occur in the United States next year will in fact occur among individuals with below-average lipid levels. For this reason, our research group has sought in our large-scale prospective epidemiologic studies to understand better other markers associated with cardiovascular risk.
Reference:
Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis 1996;124(Suppl):S1-9.
Keywords: cholesterol distribution, Framingham Heart Study
Slide type: graph
150
200
250
300
Total Cholesterol (mg/dL)
Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.
©1996 Reprinted with permission from Elsevier Science.

35. Menopause average age of the menopause 51.
Premature menopause <40 (natural or surgical) associated with elevated CVD risk.
In surgical menopause estrogen therapy significant protection against IHD.
especially if current users and starting within 1 year
POF
1% < impaired endothelial function and early onset of CHD(HR: 1.61). but not stroke Prophylactic bilateral oophorectomy before the age increased risk for CVD.

36. Menopausal symptoms and CVD risk Classic vasomotor symptoms:
40% of perimenopausal and menopausal women world-wide
severe menopausal symptoms associated with HTN, elevated T.C. and increased CVD events
compared with few or no menopausal symptoms

37. night sweats (but not hot flushes)→ modest increase in CHD risk (10y follow- up result)
Hot flushes →higher estimate of insulin resistance and B.S
Signs of subclinical atherosclerosis are more prevalent in women with severe vasomotor symptoms

38. Menopausal vasomotor symptoms: increased sympathetic and decreased parasympathetic function.
MHT: for prevention of CHD: controversial.

40. Which risk factors are more predictive in women?
Low HDL is more predictive than high LDL
Lp (a) can be more predictive in younger women
TG can be more predictive in older women, especially if >400 mg/dL
Rich-Edwards, JW et al. NEJM 1995; 332:1758; Miller VT. Atherosclerosis 1994; 108 Suppl:S73; Orth-Gomer K. Circulation 1997;95:329

41. Which risk factors are more predictive in women?
Diabetes: almost double the risk of fatal CAD
Smoking:
associated with 50% of all coronary events in women
Risk elevated even with minimal use
Zuanetti G et al. JACC 1993;22:1788; Willett WC etal.NEJM 1987;317:1303

42. Effect of smoking
Women who smoke have a six-fold increased risk of MI (vs. 3x in men)
Risk was higher for women smokers than men regardless of age
Njolstad I et al. Circulation 1996;93(3):450; Prescott E et al. BMJ 1998;316(7137):1043

43. Reproductive Pregnancy-related “failed stress test:
Pre-eclampsia – 3.8x more likely to develop DM, 11.6x more likely to develop HTN requiring rx
Gestational DM: up to 70% develop DM within 5 years
Menopause
Magnussen 2009, Kim 2002

44. Diagnosis Treadmill stress testing Nuclear stress testing Stress echo
CT calcium score
Coronary CTA
Cardiac catheterization with coronary angiography

45. Kwok Y, et a;. Am J Cardiol 1999; 83:660.
Stress Testing
ETT only (lower than in men)
61% and 70%
Stress Nuclear (similar in men)
78% and 64%
Stress Echo (similar in men)
86% and 79%
Kwok Y, et a;. Am J Cardiol 1999; 83:660.

46. Truong Q et al. Circulation 2013; 127;2494
Coronary CTA
ROMICAT trial
Women had greater reduction in LOS, lower admission rates, lower radiation doses
More normal studies, less obstructive dz
Truong Q et al. Circulation 2013; 127;2494

47. Diagnosis
Women less likely to be referred for further evaluation if they have a positive stress test
Higher incidence of MI or death in these patients
Shaw LJ et al. Ann Intern Med 1994;120:559; Hachamovitch R et al. JACC 1995; 26: 1457

48. Risk Factors/Prevention
The Multiplier Effect
1 risk factor doubles your risk
2 risk factors quadruple your risk
3 or more risk factors can increase your risk more than tenfold
By doing just 4 things – eating right, being physically active, not smoking, and keeping a healthy weight – you can lower your risk of heart disease by as much as 82 percent
NHLBI: "Heart Truth" campaign

49. Treatment/Prevention
All women
Exercise
Quit smoking
Healthy diet
BMI <25, waist circumference <35 in.
Treat risk factors: HTN, DM, dyslipidemia
ASA – look at risk/benefit ratio
Treat depression
Mosca L et al; Circulation 2011;123:1243

50. Treatment/Prevention
Increasing awareness
Screening
Mosca L et al; Circulation 2011;123:1243

51. Treatment/Prevention
Lipids: New guidelines
Different approach: moderate or high intensity statin rather for different risk categories rather than treatment to targets
Overall risk
Patient centered care
Limited role for non-statin rx

52. Treatment/Prevention
Lipids: New guidelines
4 categories:
Clinical ASCVD, no HF or ESRD on HD
Ages with DM and LDL
LDL >190
Ages 40-75, LDL , estimated 10-year risk of 7.5% or greater
New risk calculator: Pooled Cohort Equations for ASCVD risk predictionshttp:// Quality/Practice-Guidelines-and-Quality-Standards/2013- Prevention-Guideline- Tools.aspx?w_nav=Search&WT.oss=new risk calculator&WT.oss_r=3056&

53. Lipid therapy New risk calculator
Heavily driven by age, also includes ethnicity/race, BP, cholesterol, current tobacco use and DM
65 yo M or 71 yo F with optimal RF has >7.5% 10 year risk of ASCVD
If uncertain, can take into consideration other factors:
Family hx
CRP>2
Calcium score >300 or >75%
Abnormal ABI (<0.9)

54. Lipid therapy New guidelines
No clear role for CKD, apoB, albuminuria, cardiorespiratory fitness, CIMT
Lifestyle modifications
Diet high in fruits and vegetables
Keep sat fat <5-6%, minimize trans fat
Exercise: 3-4 sessions/week, 40 minutes per session to lower LDL

55. Treatment/Prevention
High risk women
Dyslipidemia (better secondary prevention data: 4S, CARE, HPS, PROVE-IT)
Aspirin
HTN
No role for vitamins or HRT
Mosca L et al; Circulation 2011;123:1243

56. Treatment in ACS or acute MI
Medical therapy
Aspirin, beta blockers, ACE-inhibitors
Statins

57. Interventional treatment in women
Less likely to be referred
Higher complication rate than in men
Smaller arteries, more bleeding
But these pts do better than if no intervention
Higher peri-procedural rate of complication but better long-term survival than men
Anand SS et al. JACC 2005;46:1845; King KM et al. JAMA 2004;291:1220; Anderson ML et al. Circulation 2012; 126:2190

58. Treatment of ACS, NSTEMI, STEMI
Early invasive strategy for high-risk patients
PCI for STEMI
Better than fibrinolysis or POBA
Glaser R et al. JAMA 2002;288:3124; Mueller C et al. JACC 2002;40:245; Lansky AJ et al. Circulation 2005;111:1611

59. Bleeding Women have more bleeding than men
Technical factors, medication issues
RISK-PCI
Same efficacy as in men
Higher bleeding
Higher mortality
Can J Cardiol 2013; 29:1097

60. Bleeding Bleeding avoidance strategies
Transradial approach, closure devices, bivalrudin
Lower bleeding rates in both sexes
Higher absolute bleeding rate
JACC 2013; 61:2070; Circ 2013; 127:2295

61. Other cardiac causes of chest pain
Women’s ischemic heart disease (syndrome X, microvascular disease)
Myocarditis
Stress-induced cardiomyopathy
Coronary dissection

62. Use of MHT for Prevention
Prevention of Diseases after Menopause
2014
Use of MHT for Prevention
In women close to menopause, consistent data from observational studies, RCTs and meta-analyses show that estrogen therapy reduces coronary heart disease and mortality with rare risks (De Villiers TJ 2013; Lobo RA 2014.) Findings in women treated with the addition of progestogen are less clear
While individualization is key, estrogen-based MHT may be considered as part of the prevention strategy for women at the onset of menopause

69. Prevention of Diseases after Menopause
2014
Conclusion
Assessment of risks for diseases assumes a great importance at the onset of menopause; with the following 10 years affording an important window for intervention
Life-style adjustments including increasing physical activity, control of body weight, mentally stimulating activity, screening for cancer and consideration of MHT are all part of this strategy

70. Take-home points
CAD and CVD are by far the biggest health risks for women
Awareness is still less than it needs to be
Prevention CAN reduce risk
Screening programs are available

71. Take-home points
Women can present differently, and do worse when they do
Women are referred less often for appropriate testing and treatment
Women can have more complications from treatment, but still fare better than without rx
Special considerations: pregnancy, menopause, comorbidities