Postmenopausal Woman: Calculating Cardiovascular Disease Risk Beth - PowerPoint PPT Presentation

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

1+1 = 4 – get your risk assessed! 8 0 4 5 3 0 20

Your Risk May be Higher Than You Think!! And double that for family history!!!! Genest J et al: 2009 Canadian dyslipidemia guidelines. Anderson et al Can J Cardiol 2016

Smoking Cessation The single most powerful preventive intervention in clinical practice Rivara FP et al . Am J Prev Med 2004; 27(2):118-25.

Visceral Adipose Tissue (VAT) The Dangerous Inner Fat! Front Visceral AT Subcutaneous AT Back

Visceral Obesity is Associated with Conditions that lead to Heart Disease Increased Diabetes LDL Insulin resistance Decreased Increased insulin levels HDL Abnormal blood clotting High TGs Glucose intolerance Blood Vessel Dysfunction

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

HOPE 3 Baseline Characteristics 12,705 randomized 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 20% Latin American 28% Chinese 29% Other Asian 20% Black African 2%

Prespecified Subgroups: By Thirds of SBP CV Death, MI, Stroke SBP Placebo Cutoffs Mean Diff P Trend Event Rate% HR (95% CI) ≤131.5 2.9 122 6.1 1.16 (0.82-1.63) 0.021 131.6-143.5 138 5.6 3.8 1.08 (0.80-1.46) 154 >143.5 5.8 6.5 0.73 (0.56-0.94) 0.5 1.0 2.0 Cand + HCTZ Better Placebo Better Lonn E, Blood pressure lowering in intermediate risk people without vascular disease . NEJM 2016.

CV Death, MI, Stroke, Cardiac Arrest, Revasc, Heart Failure 0.10 HR (95% CI) = 0.75 (0.64-0.88 ) Cumulative Hazard Rates 0.08 P-value = 0.0004 0.06 Placebo 0.04 Rosuvastatin 0.02 0.0 0 1 2 3 4 5 6 7 Years Rosuva 6361 6241 6039 2122 Placebo 6344 6192 5970 2073 Yusuf, S ., Rosuvastatin in intermediate-risk people without cardiovascular disease. NEJM 2016.

Cholesterol Lowering Arm: Change in LDL-C, Apo-B, and CRP LDL-C (mg/dL) APO B (g/L) log hsCRP (g/L) 0.8 130 Placebo Placebo Placebo 1.1 0.7 120 1.0 0.6 110 mean Δ 34.6 mg/dl* mean Δ 0.23 g/l* log mean Δ 0.19* 0.9 0.5 100 0.4 0.8 90 Rosuvastatin Rosuvastatin Rosuvastatin 0.3 0.7 80 0 Year 1 Year 3 Study End 0 Year 1 Year 3 Study End 0 Year 1 Year 3 Study End * 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.

Crude angiography rates* within 3 mos of a heart attack, by sex in Ontario, 2005/06 Men Women 39 44 56 61 * Angiography rates were determined by identifying patients who were on the CCN list for angiography within 3mos of discharge. 27 Data source(s): CIHI-DAD, 2005/06; CCN 2005/06

Fig 2: Medication management one year post AMI discharge: beta blockers, ACEi and/or ARB and statin use by sex, in Ontario 100 78 74 73 72 69 69 Percentage (%) 80 60 40 20 0 Beta blocker ACEi and/or ARB Statin Medication Women Men • 9,882 patients were hospitalized with AMI 2005/06 • 7,961 were alive one year post D/C, med use assessed www.powerstudy.ca

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