coronary artery disease · 2020-02-13 · by wael almahmeed md, fccp, frcpc, frcpe, ... clinical...

2

Coronary Artery Disease in Women

by Wael AlmahmeedMD, FCCP, FRCPC, FRCPE, FACP, FACC, FESC

Clinical Associate Professor of Medicine, UAE UniversityConsultant Cardiologist at

Cleveland Clinic, Abu Dhabi

3

Objectives1. Case Presentation2. Coronary Artery Disease in women

in the West.3. Coronary Artery Disease in women

in the Gulf States.4. Summary

4

Case Presentation59 year old woman presented to my clinic with chest pain on exertion Gets the pain after 50 metersResolves with rest

Known: Diabetes Meds: ASAObesity Lipitor 20Dyslipidemia Janumet

GlargineEmpagliflozin

5

Case Presentation (cont.)O/E : BP 120/60 P 80 Rg

CVS was normal, RS was normalECG showed non specific ST changes

Tot Cholesterol 3.65TG 1.09LDL 1.79HDL 1.36

Echo: Normal CV size and systolic function.

6

Case Presentation (cont.)Mobi scan: Large defect which is reversible in the anterior and inferior walls.

Angiography: Proximal tight stenosis of the LAD,Mid RCA stenosis

CABG: LIMA to LADSVG to RCA

The procedure was uncomplicated and she was discharged to home.

Age-adjusted prevalence of obesity in adults 20 to 74 years of age by sex and survey year (National Health Examination Survey: 1960–1962; National Health and Nutrition Examination

Survey: 1971–1974, 1976–1980, 1988–1994, 1999–2002, 2003-2006, and 2009–2012).

Mozaffarian D et al. Circulation. 2015;131:e29-e322

Copyright © American Heart Association, Inc. All rights reserved.

Prevalence of cardiovascular disease in adults ≥20 years of age by age and sex (National Health and Nutrition Examination Survey: 2009–2012).



Cardiovascular disease and other major causes of death for all males and females (United States: 2011).



Cardiovascular disease (CVD) mortality trends for males and females (United States: 1979–2011).

Mozaffarian D et al. Circulation. 2017;131:e29-e322 Copyright © American Heart Association, Inc. All rights reserved.

11

Prevalence of CAD in Women

• Coronary Artery Disease is the leading cause of death in Women.

• CAD mortality is higher in Women than Men.

• Impact of obesity is greater in Women than in Men.

• Incidence of CAD lags 10 years behind Men.• Consequences of CAD are worse in Women

than in Men.

Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013

12

• Pathophysiology of CAD is different in Women.• Women have smaller Coronary Arteries.• Less obstructive CAD.• Disorders of the microvasculature and

Endothelial dysfunction have been implicated in Women.

• Women have a greater frequency of plaque erosion and distal embolization.


13

Risk Assessment


14

Risk Assessment


15

Risk Assessment


16

Diagnosis of Myocardial Ischemia in Women

A negative exercise test is a good negative predictor of CAD in Women.


17

Management of Obstructive CAD in Women

Why is mortality due ACS in Women higher than in Women?

1. Women are treated less aggressively than men.

2. Receive less EB medicine.


18

With regards to surgery: CABG Female sex is an independent risk factor for morbidity and mortality.


19

Management of Non-Obstructive CAD

Women with myocardial ischemia and non-obstructive CAD, the prognosis was felt to be benign in the past.

More recent data has shown that the prognosis is not benign and the risk of CV events is higher than for asymptomatic women.


20

In the WISE Study:-Symptomatic women with non-obstructive CAD had an event rate of 16% vs 7.9% in Symptomatic women with no CAD and event rate was 2.4% in asymptomatic controls.


21

Treatment of Non-Obstructive CAD

1. Improve Endothelial function with Statins and ACE Inhibitors.

2. Symptoms with Beta Blockers and Imipranine and L arginine.

3. Ranolazine is promising.


22

Undertreatment of CAD• Women are still less likely to receive

preventive recommendations, such as lipid lowering, ASA, life style modification.

• Hypertensive women are less likely to have their BP at goal.

• Dyslipidemic women are less likely to reach their LDL goals, (particularly diabetic women).

• Women receive less cardiac rehabilitation.


Allam et al (JAMA 2009;302(19) )

Coronary Artery Disease in Women of the Middle East is not new. It has recently been identified in Egyptian Mummies.

Gulf RACE I

6 months prospective multi center Registry of ACS in 6 Gulf States.

8,169 consecutive patients were recruited from 64 hospitals with diagnosis of ACS, including unstable angina, STEMI and NSTEMI.

Am J Cardiol 2009;104:1018-1022.

The Distribution of Men and Women in relation to Citizenship

CitizensExpatriates

82%

48%

MenWomen

p<0.001

CitizensExpatriates

6 Middle-eastern Countries

Clinical Characteristics

Variable Men(n=6,183)

Women(n=1,983)

p Value

Age (years) 53 (16) 62 (17)

Previous angina pectoris 2,295 (37%) 1,017 (51%) 0.001

Previous MI 1,531 (25%) 463 (23%) 0.225

Previous CABG 329 (5%) 132 (7%) 0.028

Diabetes Mellitus 2,226 (36%) 1,085 (55%) 0.001

Hypertension 2,665 (43%) 1,390 (70%) 0.001

Clinical Characteristics (cont.)


Women(n=1,983)

p Value

Dyslipidemia 1,736 (28%) 872 (44%) 0.001

Current smokers 2,886 (47%) 101 (5%) 0.001

Renal impairment 807 (14%) 277 (15%) 0.22

COPD 281 (5%) 154 (8%) 0.001

Stroke 225 (4%) 153 (8%) 0.001

PVD 127 (2%) 68 (3%) 0.001

Age


Clinical Characteristics (cont.) Variable Men

(n=6,183)Women

(n=1,983)p

ValueBMI (kg/m2) 26.3 (5.4) 28.3 (8.4)

Heart Rate (beats/min) 80 (26) 88 (24)

Systolic BP (mm Hg) 136 (38) 140 (40)

Killip class > I 1,206 (20%) 568 (29%) 0.001

Ischemic Chest Pain 5,084 (82%) 1,400 (71%) 0.001

Atypical Chest pain 379 (6%) 158 (8%) 0.005

Dyspnea 499 (8%) 300 (15%) 0.001

Clinical Characteristics (cont.)


Women(n=1,983)

p Value

GRACE risk score 0.000

lLow 1,073 (46%) 84 (25%)

lMedium 702 (30%) 102 (29%)

lHigh 585 (25%) 161 (46%)

WOMEN

Ü 9 years older than menÜ more diabetesÜ more HTNÜ more obesityÜ more dyslipidemiaÜ less smokingÜ more co-morbidities

Variability

Variable Men Women p Value

STEMI at discharge 2,749 443

Presentation > 12 hrs 731 (28%) 173 (42%) 0.001

Door-to-needle time 35 (40) 40 (50)

Eligible for reperfusion 1,929 (73%) 244 (59%) 0.001

Shortfall 153 (8%) 37 (15%) 0.001

Variability (cont.) Variable Men Women p Value

Thrombolysis 1,613 (84%)* 195 (80%)* 0.172

Primary PCI 163 (8%) 12 (5%) 0.074Asprin 2,617 (96%) 408 (98%) 0.474Beta Blockers 1,682 (63%) 234 (56%) 0.006ACE inhibitors/ARBs 1,824 (69%) 272 (65%) 0.211

Clopidogrel 1,588 (60%) 229 (55%) 0.073

Heparin 2,438 (92%) 383 (92%) 0.971

Glycoprotein inhibitors 239 (9%) 9 (2%) 0.003

Statins 2,238 (81%) 354 (80%) 0.35

0

10

20

30

40

50

60

70

80

90

100

MenWomen

Lytics Pri PCI Aspirin b-blockers Clopidogrel

84%*

80%*

96% 98%

63%56% 60%

55%

5%8%

P=NS

P=07

P=NS

P=.006P=.07

* Of patients eligible for thrombolysis.


Variability (cont.) Variable Men Women p Value

Death 137 (5%) 62 (14%) 0.0000

Heart failure 420 (15%) 128 (29%) 0.0000Cardiogenic shock 204 (7%) 91 (21%) 0.0000Reinfarction 77 (3%) 21 (5%) 0.02

Recurrent ischemia 241 (9%) 69 (16%) 0.000

Stroke 23 (1%) 13 (3%) 0.002

Major bleeding 28 (1%) 7 (2%) 0.38Hospital stay 5 (3) 6 (4)

0

5

10

15

20

25

30

Death CHF Shock Re-MI Stroke

MenWomen

Hospital Outcome

5%

14% 15%

29%

7%

21%

3%5%

1%3%

P<0.001

P<0.001

P<0.001

P=0.02

P=0.002


0

2

4

6

8

10

12

14

STEMI NSTEMI U.Angina

MenWomen

Mortality Rate Stratified According to type of ACS and Gender

5%

14%

2%

4%

1% 1.2%

P=0.001

P=0.007

P=0.68


WOMEN

Ü presented more often after 12 hrsÜ STEMI missed in women compared to men

(6% vs 3%)Ü HR highÜ BP highÜ presented with more dyspnea and atypical

chest pain.Ü heart failure was more prevalent in women

Women

Less likely to receive thrombolysis, primary PCI

and have a prolonged door- -to-needle time.

WOMEN:Ü Received less EB medicines verses the men.Ü Had high GRACE scoresÜ Higher morbidityÜ High in Hospital mortalityÜ Higher :- heart failure

cardiogenic shockrecurrent ischemiastroke

Multivariate Analysis Predictor OR 95% CI p Value

Female gender 1.75 1.10 - 2.781 0.01

PCI 0.50 0.15 - 1.73 0.27Asprin 0.25 0.12 - 0.70 0.008Clopidogrel 0.96 0.64 - 1.46 0.87Glycoprotein IIb/IIIb 0.51 0.18 - 1.39 0.18

Beta blockers 0.37 0.23 - 0.59 0.000

ACE Inhibitors 0.43 0.28 - 0.65 0.000

Thrombolysis 0.52 0.34 - 0.81 0.003

After adjustment for Age, HR, DM, HTM, GRACE Risk Score:

Female gender comes associated with increased in hospital mortality.

Under use of EB therapies was also associated with increased mortality.

This is the 1st study from the Middle East to show that Women with ACS had a high mortality rate

compared to men, after adjustment of all co-founders.

It confirms previous studies that women have different risk profiles :-

Ü Present lateÜ Atypical symptomsÜ Longer door-to-needle timesÜ Less perfusion therapies

Recognition of gender differences will lead to a number of quality

improvement projects to improve the process of care.

Physician and public awareness programs are important to improve the

management of women with ACS.

49

Gender Differences in Gulf RACE2

Females comprised 21.3% of the ACS population.

Baseline characteristics:Females were; Older

Higher BMIMore NSTEMI, UAmore HTNDiabetesDyslipidemiaMore atypical chest pain

Shehab A, et al; Plos One, 2013; Vol 8.

50


Medical treatment:Males received more: Beta Blockers

Clopidogrel Females received more: CCB

ARBsInsulin and OHA

Men had more PCI vs Women: 15.6% vs 10.5%Men had more reperfusion 20.2% vs 6.9therapy


51


At discharge:

Men got more: ASA PlavixBeta BlockersACEStatins


Figure 1. Proportion of patients dying in-hospital and within one year from hospital discharge (n = 6132).

Shehab A, Al-Dabbagh B, AlHabib KF, Alsheikh-Ali AA, et al. (2013) Gender Disparities in the Presentation, Management and Outcomes of Acute Coronary Syndrome Patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). PLoS ONE 8(2): e55508. doi:10.1371/journal.pone.0055508http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055508

53

Clinical Outcomes & Mortality

Recurrent ischemiaCHFVentilationShockIn Hospital DeathDeath at 1 monthDeath at 1 year

Were all higher in Women.


Figure 2. Association of gender (female) and mortality derived from multivariate-adjusted analyses (n = 7930).


55

Clinical Outcomes & Mortality

When adjusting for:

Age BMI presenting SymptomsCountry Killip class medical historyDiagnosis Tobacco invasive proceduresMedications

There is no difference in the 1 year mortality between genders


Table 3. In-hospital outcomes and 1-month and 1-year post discharge mortality of the study cohort by gender (n = 7930).


57

Gulf RACE II

Women presented with more NSTEMI/UA70.2% vs 50.2%

While Men presented with STEMI49.8% vs 29.8%

Women had more HTNDMDyslipidemia


58

Gulf RACE II

Women are treated more conservatively. This may have been due to the following:

1. More co-morbidities2. Atypical presentation3. Patient preference4. Physicians preference or Fear


59

Gulf RACE II

In this Study, in contrast to Gulf RACE I, the Multivariate Regression Models indicated that most of the differences in mortality can be explained by the confounding baseline variables and the differences in management.

Greater awareness of CAD in Women may eliminate the gender gap.


IsthereagenderdisparityinachievingLipidtargetsinpatientsintheArabianGulf?

CEPHUESStudy :-• MultiCenterStudyofLipidloweringintheArabianGulf.

• 5457patientswereenrolled• Afastingbloodsampleweretakenfromeachpatientforlipids.

• 40%(1763)ofthepatientswerefemales.

Zakwani et al; Current Vascular Pharmacology, 2017; 15.

Characteristic,n(%)unlessspecifiedotherwise

All(n=4,384)

Female(n=1,763)

Male(n=2,621)

P

Gulfcitizen 3,298(75%) 1,558(88%) 1,740(66%) <0.001Age,mean±SD,years 57±11 57±10 56±11 0.013Weight,mean±SD,kg 82±17 79±17 84±17 <0.001Waistcircumference,mean±SD,cm

104±14 104±14 104±14 0.709

BMI,mean±SD,kg/m2 31±7 34±8 30±6 <0.001Currentsmoker 561(13%) 35(2.0%) 526(20%) <0.001CHD 1,611(37%) 366(21%) 1,245(48%) <0.001PAD 149(3.4%) 54(3.1%) 95(3.6%) 0.314CVD 191(4.4%) 66(3.7%) 125(4.8%) 0.103Diabetesmellitus 3,336(76%) 1,486(84%) 1,850(71%) <0.001MetS 1,786(41%) 869(49%) 917(35%) <0.001ASCVDriskfactors0 110(2.5%) 67(3.8%) 43(1.6%)1 659(15%) 365(21%) 294(11%)2 1,568(36%) 673(38%) 895(34%) <0.0013 1,568(36%) 561(32%) 1,007(38%)4 428(9.8%) 93(5.3%) 335(13%)5 51(1.2%) 4(0.2%) 47(1.8%)

ASCVDriskstatusHighrisk 959(22%) 511(29%) 448(17%) <0.001Veryhighrisk 3,425(78%) 1,252(71%) 2,173(83%) <0.001

Table 1 Demographic and clinical characteristics of the CEPHEUS cohort stratified by gender


Dyslipidaemic therapy

Statinmonotherapy 4,122(94%) 1,693(96%) 2,429(93%) <0.001

Simvastatin 1,785(43%) 862(51%) 923(38%) <0.001

Atorvastatin 1,779(43%) 668(39%) 1,111(46%) <0.001

Rosuvastatin 486(12%) 142(8.4%) 344(14%) <0.001

Statincombination 220(5.0%) 61(3.5%) 159(6.1%) <0.001

Others 42(1.0%) 9(0.5%) 33(1.3%) 0.013

Lipidlevelsontreatment,mean±SD,mmol/L,unlessspecifiedotherwiseTC 4.30±1.11 4.52±1.12 4.15±1.09 <0.001

LDL-C 2.53±0.94 2.64±0.94 2.46±0.93 <0.001

HDL-C 1.15±0.31 1.28±0.32 1.06±0.27 <0.001

ApoB,g/L 0.91±0.27 0.94±0.28 0.90±0.27 <0.001

Non-HDL-C 3.15±1.09 3.24±1.11 3.09±1.07 <0.001

TG 1.74±1.26 1.70±1.24 1.77±1.28 0.063


All(n=4,384)

Female(n=1,763)

Male(n=2,621)

P


Lipidgoalattainments,n(%)

HDL-Cgoal 2,058(47%) 745(42%) 1,308(50%) <0.001

LDL-Cgoal 1,340(31%) 493(28%) 847(32%) 0.002

ApoBgoal 1,775(41%) 674(38%) 1,101(42%) 0.015

Non-HDL-Cgoal 1,809(41%) 713(40%) 1,096(42%) 0.365

SD standarddeviation,BMI bodymassindex,CHD coronaryheartdisease,PAD peripheralarterialdisease,CVDcardiovasculardisease,MetSmetabolicsyndrome,ASCVD atheroscleroticcardiovasculardisease,HDL-C high-densitylipoproteincholesterol,LDL-C low-densitylipoproteincholesterol,ApoB apolipoproteinB,TG triglyceride.

CriteriaforASCVDriskstatuswasadaptedfromtheNationalLipidAssociation.Highriskgroupincludedpatientswith≥3majorASCVDriskfactors,diabetesmellitus(type1or2)with0/1majorASCVDriskfactors,LDL-C≥190mg/dL(5.02mmol/L)(severehypercholesterolemia).VeryhighriskgroupincludedASCVD(CHD,PAD,CVD),diabetesmellituswith≥2othermajorASCVDriskfactors.

DespitethelackofarecommendedHDL-Cgoalbyguidelines,satisfactoryHDL-Cwasdefinedas<40mg/dL(1.04mmol/L)formalesor<50mg/dL(1.3mmol/L)forfemales.TherapeuticlipoproteintargetsforthehighriskpatientswereLDL-C<2.6mmol/L,apoB<0.90g/Landnon-HDL-C<3.3mmol/L.ForthehighestriskgrouptherapeuticlipoproteintargetswereLDL-C<1.8mmol/L,apoB<0.80g/Landnon-HDL-C<2.6mmol/L.

Agewasmissingin8patients,weightin4patients,waistin123patients,BMIin15patients,MetSin26patientsandApoBin14patients.


All(n=4,384)

Female(n=1,763)

Male(n=2,621)

P


Womenwerelesslikelytoattain… HDLCGoals

LDLCGoalsApoBGoals

TherewasnodifferenceinNon-HDLGoal.

WomenwithveryhighASCVDwerelesslikelytobetreatedwithpotentStatins.


LDL-Clow-densitylipoproteincholesterol,ApoBapolipoproteinB.

TherapeuticlipoproteintargetsfortheveryhighASCVDriskgroupwereLDL-C<70mg/dL (<1.8mmol/L),ApoB<80mg/dL (<0.80g/L)andnon-HDL-C<100mg/dL (<2.6mmol/L).WhereasforthehighASCVDriskcohort,lipidtargetattainmentswereLDL-C<100mg/dL (2.6mmol/L),ApoB<90mg/dL(0.90g/L)andnonHDL-C<130mg/dL (3.3mmol/L).

LipidgoalattainmentsforLDL-C,nonHDL-CandApoBbetweenveryhighASCVDriskwomenandmenwereallsignificant(P≤0.001).

Fig1 Overalllipidtargetachievements(LDL-C,nonHDL-CandApoB)inhighandveryhighatheroscleroticcardiovasculardisease(ASCVD)riskcohortstratifiedbygender(N=4,384)

LDL-Clow-densitylipoproteincholesterol,ApoBapolipoproteinB.TherapeuticlipoproteintargetsfortheveryhighASCVDriskgroupwereLDL-C<70mg/dL (<1.8mmol/L),ApoB<80mg/dL (<0.80g/L)andnon-HDL-C<100mg/dL (<2.6mmol/L).WhereasforthehighASCVDriskcohort,lipidtargetattainmentswereLDL-C<100mg/dL (2.6mmol/L),ApoB<90mg/dL(0.90g/L)andnonHDL-C<130mg/dL (3.3mmol/L).LipidgoalattainmentsforLDL-C(p<0.001),nonHDL-C(P=0.055)andApoB(P=0.028)betweenveryhighASCVDriskwomenand menwereallsignificantormarginalsignificant.

Fig2. Overalllipidtargetachievements(LDL-C,nonHDL-CandApoB)inthosewithtriglycerides(>200mg/dL/2.26mmol/L)andhighandveryhighatheroscleroticcardiovasculardisease(ASCVD)riskcohortstratifiedbygender(N=844)


Studyname(country)Year

N LDL-Cgoal Women(percentage)

Age(years) LDL-CgoalachievementWomen Men P

LAP(USA)2000

4,888 NCEPguidelines 49.6% 60 39% 37% 0.145*

LAP-2(USAandEurope)2009

9,955 NCEPguidelines 45.3% Women:63Men:61

71.5% 73.7% 0.014

EUROASPIREIII(Europe)2010

8,966 <100mg/dLinCHDsecondaryprevention

25.3% Women:66Men:62

45.2% 53.7% <0.001

JapansocietyofNingenDockdatabase(Japan)2013

17,991 JASguidelineinprimaryprevention;

<100mg/dLinCHDsecondaryprevention;

39.2%

17.8%

Women:61Men:57

78.1%

28.3%

73.6%

48.0%

<0.001

<0.001

TLRS(China2013

1,584 <100mg/dLinCHDsecondaryprevention


45.2% 52.9% 0.008

ChenCYetal(China)2013

1,808 Chineseguideline** 37.3% Women:62Men:64

46.0% 53.8% 0.001

LiXetal(China)2009

4,778 <100mg/dLinCHDsecondaryprevention;

<70mg/dLinCHDsecondaryprevention


28.5%

9.0%

45.5%

11.9%

<0.001

<0.001

CEPHEUS– thecurrentstudy(ArabianGulf)2015

4,384 <100mg/dL<70mg/dL

53.3%36.6%

Women:57Men:56

43.0%26.7%

43.6%31.2%

0.9020.002

LDL-C low-density lipoprotein cholesterol, NCEP National Cholesterol Education Program, CHD coronary heart disease, JAS Japan Atherosclerosis Society.*Even though not significant overall, the differences were more apparent in very high ASCVD risk status (P = 0.006).**Chinese Guidelines on the Prevention and Treatment of Dyslipidemia in Adults.

Table 2 Gender disparity in the LDL-C goal attainment in observational studies


Thereasonsforthisgenderdisparityarenotknown.

Maybebecausethereismoreobesity,DM,MSanddyslipidemiainwomen.

OneofthewarningstoreduceCVRiskinwomenistousehighdosemorepotentStatinsinordertoattainLipidtargets.


Summary of Statin Initiation Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults (See Figures 3, 4, and 5 for More Detailed Management Information).

Stone N J et al. Circulation. 2014;129:S1-S45


Menopausal Hormone Therapy, SERMs and CVD: Summary of Major Randomized Trials§ Use of estrogen plus progestin associated with

a small but significant risk of CHD and stroke§ Use of estrogen without progestin associated with

a small but significant risk of stroke§ Use of all hormone preparations should be limited

to short term menopausal symptom relief§ Use of a selective estrogen receptor modulator (raloxifene) does

not affect risk of CHD or stroke, but is associated with an increased risk of fatal stroke

Source: Hulley 1998, Rossouw 2002, Anderson 2004, Barrett-Connor 2006

Interventions that are not useful/effective and may be harmful for the prevention of heart disease§ Hormone therapy and selective estrogen-receptor modulators

(SERMs) should not be used for the primary or secondary prevention of CVD

Source: Mosca 2007

Comparison of Hospital Mortality and Readmission Rates for

Medicare Patients Treated by Male vs Female Physicians

Ref: Tsugawa, et al; JAMA Internal Medicine 2016.7875

75

Analyzed 20% sample of medicarebeneficiaries 65 years or older.

They looked at association between physician sex and 30 day mortality and readmission rates.

77

Elderly hospitalized patients treated by female internists have a lower mortality and readmissions compared with these cared for by male internists.

HEART DISEASE IN WOMENSummary

1. Less obstructive CAD.2. More chest pain without obstructive CAD. 3. Symptoms do not correlate with severity of

stenoses.4. Young and middle aged women show high

rates of adverse outcomes after MI.

Vaccarino, Circ Cardiovasc Quality Outcomes, 2010

Ü Women do worse than men when they have an STEMI.

Ü Sex differences are found in younger women with MI.

Ü These women have a higher rate of risk factors and co-morbidities compared to men.

Ü Sex differences in EB medications are significant.

Ü There are larger differences in reperfusion therapy.

Ü Also differences in catheterization and revascularization.

81

Summary1. Introduction2. Case Presentation3. Coronary Artery Disease in women

in the West.4. Coronary Artery Disease in women

in the Gulf States.

coronary artery disease · 2020-02-13 · by wael almahmeed md, fccp, frcpc, frcpe, ... clinical...

Documents