Dyslipidemia and the

Postmenopausal Woman:

Calculating

Cardiovascular Disease Risk

Beth L. Abramson MD MSc FRCP FACC

Paul Albrechtsen Professor in Cardiac Prevention & Women’s Health

Associate Professor of Medicine, U. of Toronto

Director: Cardiac Prevention Centre & Women ’s CV Health,

Division of Cardiology, St. Michael ’s Hospital

Beth L. Abramson MD MSc FRCP FACC- Disclosure

Speaker for various pharmaceutical companies including:

Amgen, Astra Zeneca, Boehringer Ingelheim, Bristol Myer

Squibb, Dupont, Eli Lilly, Norvartis, Fournier, Merck Frosst,

Pfizer, Servier, Sanofi- Aventis

Ongoing research with funds from:

Astra Zeneca, Sanofi,

National Advisory Board – Astra Zeneca, Boehringer-

Ingelheim, Novartis, Sanofi-Aventis, Amgen

Author: Heart Health for Canadians

What is Women’s health?

• More than gynecological needs

• More than breast cancer evaluation

• More than obstetrical needs

Atherothrombosis…KILLS

It’s an equal opportunity killer!

Risk Increases in Women after the Menopause

Courtesy S. Hayes MD

Courtesy Dr. N. Wegner

Update on New Risk Indicators

for Cardiac Disease:• New indicators:

• Age, Sex, BP, Smoking, Family Hx.,

cholesterol

• = composite risk score (such as

Framingham)

• Pregnancy related HT /DM

• HOPE 3 POPULATION….

Most heart attacks aren’t

sudden…they take many years of

preparation!

Risk Assessment…A Case:

• Mrs. Smith– 56 year old retired teacher

• PMH borderline HT treated with HCTZ

• + Fam Hx. Brother heart attack age 54

• still smoking despite attempts to quit

– Annual Exam includes cardiac risk assesment

• mild symptoms of menopause, otherwise no complaints

– O/E HR 72 BP 140/70 waist circ. 88 cm

• Normal exam

• T. Chol: 6.2 (235mg/dl) , HDL: 1.22 (47mg/dl), LDL 3.4

(129 mg/dl)

? Risk

8 0 4 5 3 0 20

1+1 = 4 – get your risk assessed!

And double that for family history!!!!

Your Risk May be Higher Than You Think!!

Genest J et al: 2009 Canadian dyslipidemia guidelines.

Anderson et al Can J Cardiol 2016

The single most powerful preventive intervention in clinical practice

Smoking Cessation

Rivara FP et al. Am J Prev Med 2004; 27(2):118-25.

Visceral Adipose Tissue (VAT) The Dangerous Inner Fat!

Visceral AT

Subcutaneous AT

Front

Back

Increased

LDL

Decreased

HDL

High TGs

Diabetes

Insulin resistance

Increased insulin levels

Abnormal blood

clotting

Glucose intolerance

Blood Vessel

Dysfunction

Visceral Obesity is Associated with Conditions

that lead to Heart Disease

Increased future risk for heat attack and

stroke?

High BP in Pregnancy (Pre-eclampsia)

and risk of future CV Disease• Hypertension 3.70 (2.7-5.05)

• Ischemic Heart Disease 2.16 (1.86-2.52)

• Major Stroke: 1.81 (1.45-2.27)

• Premature CV Death 1.49 (1.05-2.14)

• Premature CVD (severe PE + IUGR):

8.12 (4.31-15.33)

Graeme N. Smith Queens University

Diagnosis of the Patient at Risk

HOPE 3 TRIAL

• Moderate risk individuals

• 46% women.

• BP lowering effect

• Statins to lower event rates

NEJM 2016

Intermediate-Risk Population

Inclusion Criteria (Target Risk 1.0%/yr)

Women ≥ 60 yrs, men ≥ 55 yrs

with at least one additional Risk Factor

• Increased WHR • Dysglycemia

• Smoking • Mild renal dysfunction

• Low HDL-C • Family history of CHD

Exclusion Criteria:

CVD or indication(s) or contraindication(s) to study drugs

No strict BP or LDL-C criteria for entry

Uncertainty principle

HOPE 3 Inclusion:• Women > 65 years* and men aged ≥ 55 years

• At least one of the following additional CV risk factors:

• Waist/hip ratio ≥ 0.85 in women and ≥ 0.90 in men

• History of current or recent smoking (regular use within 5 years)

• Low HDL-C [ HDL-C < 1.0 mmol/L (38 mg/dl) in men and <1.3

mmol/L ( 49 mg/dl) in women]

• Pre – early diabetes - uncomplicated diabetes treated with diet

• Early kidney dysfunction

• Family hx CAD (first degree relatives, men < 55 or women <65)

• * women > 60 with at least 2 risk factors were also eligible

Age (yrs) 66

Female 46% (n = 5500)

Blood Pressure (mmHg) 138/82

LDL-Cholesterol (mmol/L) 3.3 (128 mg/dl)

Elevated waist-to-hip ratio 87%

hsCRP (g/L) median 2.0

Ethnicity

White Caucasian

Latin American

Chinese

Other Asian

Black African

20%

28%

29%

20%

2%

HOPE 3 Baseline Characteristics12,705 randomized

Prespecified Subgroups:

By Thirds of SBPCV Death, MI, Stroke

0.5 1.0 2.0

Cand + HCTZ Better Placebo Better

SBP

Mean

≤131.5

131.6-143.5

>143.5

Diff

6.1

5.8

2.9

3.8

6.5

HR (95% CI)

1.16 (0.82-1.63)

1.08 (0.80-1.46)

0.73 (0.56-0.94)

P Trend

0.021

5.6

Cutoffs

122

138

154

Placebo

Event Rate%

Lonn E, Blood pressure lowering in intermediate risk

people without vascular disease. NEJM 2016.

CV Death, MI, Stroke,

Cardiac Arrest, Revasc, Heart Failure

Years

Cu

mu

lati

ve H

azard

Rate

s

0.0

0.0

20

.04

0.0

60

.08

0.1

0

0 1 2 3 4 5 6 7

Placebo

Rosuvastatin

HR (95% CI) = 0.75 (0.64-0.88)

P-value = 0.0004

6361 6241 6039 2122

6344 6192 5970 2073

Rosuva

Placebo

Yusuf, S., Rosuvastatin in intermediate-risk people without

cardiovascular disease. NEJM 2016.

Cholesterol Lowering Arm:Change in LDL-C, Apo-B, and CRP

0 Year 1 Year 3 Study End

80

90

10

01

10

12

01

30

Placebo

Rosuvastatin

LDL-C (mg/dL)

0 Year 1 Year 3 Study End

0.7

0.8

0.9

1.0

1.1

APO B (g/L)

0 Year 1 Year 3 Study End

0.3

0.4

0.5

0.6

0.7

0.8

log hsCRP (g/L)

mean Δ 34.6 mg/dl* mean Δ 0.23 g/l* log mean Δ 0.19*

Placebo

Rosuvastatin

Placebo

Rosuvastatin

* P< 0.001

Prospective meta-analysis: 90,056

participants in 14 randomized statin trials

• For each 1 mmol/L (38 mg/dl) LDL-C lowering

– 12% reduction in all cause mortality (p<0.0001)

– 19% reduction in coronary mortality (p<0.0001)

– 23% reduction in MI and coronary death (p<0.0001)

– 24% reduction in revascularizations (p<0.0001)

– 17% reduction in fatal or non-fatal stroke (p<0.0001)

– 21% reduction in any major vascular event (p<0.0001)

– no increase in non-vascular mortality or cancers

Adapted from Baigent C, et al, Cholesterol Treatment Trialists’ (CTT) Collaborators. Lancet

2005;366:1267–1278.

27

Crude angiography rates* within 3 mos of a

heart attack, by sex in Ontario, 2005/06

Women

44

56

Men

61

39

* Angiography rates were determined by identifying patients who were on

the CCN list for angiography within 3mos of discharge.

Data source(s): CIHI-DAD, 2005/06; CCN 2005/06

69 73 7269 74 78

0

20

40

60

80

100

Beta blocker ACEi and/or ARB Statin

Medication

Percenta

ge (

%)

Women Men

Fig 2: Medication management one year post AMI discharge: beta blockers,

ACEi and/or ARB and statin use by sex, in Ontario

www.powerstudy.ca

•9,882 patients were hospitalized with AMI 2005/06

• 7,961 were alive one year post D/C, med use assessed

CV Risk Reduction in Women -

summary:• CVD is a leading cause of female death

• Risk is underestimated in PM women – to

sort this out use proven risk assessment

tools

• High BP and DM in pregnancy puts women

at future risk

• Women at moderate Risk – 65+ with another

risk benefit from statin therapy.

• Lipid lowering under prescibed in PM women