Sex Differences in Cardiovascular Aging – Cardiovascular Disease, Cognition and Health Policy

Overview: Can Inclusion of Women Improve Men’s Heart Health?

C. Noel Bairey Merz MD Medical Director Barbra Streisand Women’s Heart Center Smidt Heart Institute Cedars-Sinai Medical Center

https://www.statista.com/statistics/274513/life- expectancy-in-north-america/

Average Life Expectancy for North America for those born in 2018 by gender and region (years)

What can we learn about female aging that can improve human health for women and men?

https://www.statista.com/statistics/274513/life-

Sex Differences in Cardiovascular Aging Which May Lead to Improved Men’s Health

1) Coronary Microvascular Dysfunction

2) Coronary Arterial Remodeling 3) Left Ventricular Remodeling

Younger women: Plaque erosionYounger women: Plaque erosion:: Thrombus over a base rich in smooth muscle with proteglycan-rich matrix (necrotic core -

often absent): 40% of thrombi in sudden cardiac death

Men and older women: Plaque ruptureMen and older women: Plaque rupture:: Thin fibrous cap over large necrotic core Infiltrated by foamy macrophages: 60% of thrombi

in sudden cardiac death

Source: Burke Circulation 1998;97:2110-2116.

Plaque E rosion Plaque Rupture

1615PC Bairey-Merz/Slide # 6

Morphology of Intramyocardial Emboli in Epicardial Plaque Thrombosis

Women vs. men: – Any emboli: 73% vs. 37%, p

INOCA (ischemia with no obstructive CAD): Cardiac MRI demonstrating microvascular coronary dysfunction.

8

WARRIOR: Women’s IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl J. Pepine MD C. Noel Bairey Merz MD

Eileen Handberg PhD Rhonda Cooper-DeHoff PharmD

Janet Wei MD Andre Rogatko PhD

Bernard Chaitman MD William Weintraub MD

4,422 subjects with angina, no obstructive CAD randomized to IMT (intensive statin and

ACE/ARB) vs UC (usual care primary risk factor management) for reduction of MACE (all-cause death, non-fatal-MI, -stroke, or hospitalization for chest pain or HF) funded by the

Congressionally Directed Medical Research Program, Department of Defense, USA (NCT03417388)

Normal Coronaries

22%

1V Non-Obstructive

CAD 14%

2V Non-Obstructive

CAD 8%

3V Non-Obstructive

CAD 3%

1V Obstructive

CAD 23%

2V Obstructive

CAD 14%

3V/LM Obstructive

CAD 16%

37,674 male VA patients – 47% non-obstructive CAD

Sex Differences in Cardiovascular Aging

1) Coronary Microvascular Dysfunction

2) Coronary Arterial Remodeling 3) Left Ventricular Remodeling

Female coronary arteries enlarge when transplanted into males (JACC 2003;41:1539-46)

Women erode Men explode

WISE Study: Sex Differences in Heart Attack Plaques

Burke et al Circ 1998

Female BM-MNCs were more beneficial than male cells

Nelson, Zenovich, …Taylor

Circ Res 2007

Exploratory Clinical Study to Evaluate the Potential Bioactivity of CLBS14 in Patients with Coronary

Microvascular Dysfunction

October 6, 2017 NHLBI-SBIR

Incidence of Myocardial Infarction 46,086 hospitalized predominantly male patients with

myocardial infarction over 18,691,131 person-years

RESULTS

Age-Sex-Adjusted Incidence of Myocardial Infarction by Year

0

50

100

150

200

250

300

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Year

Inci

denc

e(p

er 1

00 0

00 p

erso

n-ye

ars)

Any MI NSTEMI

STEMI

Outpatient Medication Use Prior to Myocardial Infarction

0

10

20

30

40

50

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Year

Prop

ortio

n of

Use

(%)

ACE-I/ARB

Thienopyridine

Non-Statin Lipid Lowering

β-Blocker

Statin

STEMI

Alan S. Go, MD Kaiser Division of Research University of California, San Francisco

STEMI-related large plaque ruptures are going away

Due to outpatient meds

Chart1

1999199919998.19769223848.19769223845.72761449025.72761449026.22881463546.2288146354

2000200020008.29842488678.29842488675.52870830715.52870830716.51076308616.5107630861

2001200120017.8626460487.8626460485.17284049975.17284049976.24124363646.2412436364

2002200220027.60142709437.60142709434.9766609244.9766609246.02292455496.0229245549

2003200320037.61887497687.61887497684.52411873484.52411873486.38209130076.3820913007

2004200420047.40734702747.40734702743.94890218393.94890218396.47783520816.4778352081

2005200520057.17092917577.17092917573.68948370213.68948370216.33773862636.3377386263

2006200620066.85511261956.85511261953.54989771283.54989771286.04065251756.0406525175

2007200720076.5372615166.5372615163.30714879643.30714879645.79701326735.7970132673

2008200820086.34786738736.34786738733.1462126373.1462126375.67680531155.6768053115

All MI

STEMI

NSTEMI

Year

Incidence(per 100 000 person-years)

Age-Sex-Adjusted Incidence of Myocardial Infarction by Year

273.7707149768

132.552159238

154.7884789612

287.0015151655

126.8339192138

172.350547134

279.4333270003

119.7200145469

172.8511411731

276.1284567018

116.5800953663

171.0215123158

279.2178726307

96.8048451433

193.2662462824

268.0628211507

74.7613045283

202.4963773569

256.6155147841

66.6504276817

198.1607966138

238.2706216596

62.6774328869

183.1075801505

218.9983888943

55.0165274653

170.5308384734

208.458666459

50.2315304458

165.2407978591

Incidence with revision

CRUDEDecline over study period for MI0.1313684725

BurdenSTEMI0.58752082260.4124791774

All19992000200120022003200420052006200720080.5798666564

Rate3.0234428513.20531441823.2103203053.23549883243.28942173233.20166298793.13547553962.95180026272.70632165532.6262577819302.3442851022320.5314418191321.0320304992323.5498832369328.9421732312320.1662987935313.5475539562295.1800262709270.6321655275262.6257781927ALAN: FIGURES FOR SENS ANAL ARE BELOW

LCI2.94135151973.1212569623.1286718873.154303253.20774530113.12113811543.05644599042.87564191712.633624662.554765209294.1351519727312.1256962031312.867188699315.4303249967320.7745301146312.1138115357305.6445990449287.5641917103263.3624660046255.4765208974

UCI3.10553418233.28937187443.2919687233.31669441483.37109816353.28218786053.21450508873.02795860832.77901865052.6977503549310.5534182316328.9371874352329.1968722994331.6694414772337.1098163478328.2187860513321.4505088674302.7958608315277.9018650504269.7750354879

Error Bars8.20913312948.40574561618.16484180028.11955824038.16764311668.05248725787.90295491127.61583456067.26969952297.1492572952

STEMI8.20913312948.40574561618.16484180028.11955824038.16764311668.05248725787.90295491127.61583456067.26969952297.1492572952

Rate1.35593666151.32952264711.25515469751.24858430351.02731739550.80186553670.73992452370.69357843640.6043982810.5592956387135.5936661454132.9522647144125.5154697456124.8584303508102.731739545580.186553674473.992452372369.35784363660.439828101555.9295638744

LCI1.300961551.27538631921.20410158551.19814481050.9816728070.76156665340.70153333970.65666182680.57004340670.5263033103130.0961550014127.5386319244120.4101585538119.814481045298.167280702976.156665335970.153333969965.666182675657.004340666152.6303310271

UCI1.41091177291.3836589751.30620780941.29902379661.07296198390.84216442010.77831570770.7304950460.63875315540.5922879672141.0911772894138.3658975045130.6207809374129.9023796564107.296198388184.21644201377.831570774773.049504596463.875315536859.2287967216

Error Bars5.4975111445.41363279015.10531119185.04394930564.56445884264.02988833853.83911840243.69166096043.43548743533.2992328473

NSTEMI5.4975111445.41363279015.10531119185.04394930564.56445884264.02988833853.83911840243.69166096043.43548743533.2992328473

Rate1.66750618961.8757917711.95516560751.98691452892.26210433692.39979745122.39555101582.25822182632.10192337432.0669621432166.7506189568187.5791771047195.5165607536198.6914528862226.2104336857239.9797451191239.5551015839225.8221826349210.1923374261206.6962143183

LCI1.60654125051.81148847461.89144713361.9232860752.19437243192.33008192132.32647289612.19160908332.03785625542.0035374299160.6541250497181.1488474571189.1447133561192.3286074991219.4372431853233.0081921345232.6472896132219.1609083268203.7856255366200.3537429945

UCI1.72847112861.94009506752.01888408152.05054298272.32983624192.4695129812.46462913552.32483456942.16599049322.1303868564172.8471128638194.0095067522201.8884081511205.0542982732232.9836241861246.9512981036246.4629135545232.483456943216.5990493155213.0386856421

Error Bars6.0964939076.43032964756.37184739756.36284538716.77319050046.97155298456.90781197066.66127430816.40671188956.3424713238

Incident6.0964939076.43032964756.37184739756.36284538716.77319050046.97155298456.90781197066.66127430816.40671188956.3424713238

All

Rate2.46509243662.61148768972.58727066282.64793085712.67867995792.6100201912.51373009272.34372271772.16609429712.077312573246.5092436593261.14876897258.7270662771264.7930857093267.8679957924261.0020191023251.3730092672234.3722717724216.6094297083207.7312573031

LCI2.39077800562.53540483852.51376173582.57425345032.60473329992.53705864952.44270498412.27559876732.10080139972.013476311239.0778005638253.5404838481251.3761735848257.4253450251260.473329993253.7058649475244.27049841227.5598767347210.0801399691201.3476310969

UCI2.53940686752.68757054092.66077958972.72160826392.75262661592.68298173262.58475520122.41184666812.23138719452.1411488351253.9406867547268.757054092266.0779589694272.1608263935275.2626615917268.298173257258.4755201243241.18466681223.1387194475214.1148835092

Error Bars7.43144309557.60828512197.35089269237.36774068427.39466579937.29615415487.10251085716.81239503766.52928973926.3836262062

STEMI7.43144309557.60828512197.35089269237.36774068427.39466579937.29615415487.10251085716.81239503766.52928973926.3836262062

Rate1.2130097631.17938153731.12863498551.13345528830.9437285470.73957651060.66447728140.62729504010.55433160580.5096258476121.3009762979117.9381537284112.8634985483113.345528828494.372854696973.957651059766.447728135562.72950401355.433160582950.9625847563

LCI1.16087964591.12825222511.08008423971.08525127380.89983691970.70073790560.62796048640.59205124760.5213013390.4780072759116.0879645913112.82522251108.0084239728108.525127380689.983691965770.073790561462.796048642659.205124760652.130133900247.8007275883

UCI1.265139881.23051084951.17718573121.18165930280.98762017430.77841511560.70099407630.66253883270.58736187270.5412444192126.5139880045123.0510849468117.7185731237118.165930276298.762017428277.84151155870.099407628366.253883265358.736187265654.1244419242

Error Bars5.21301170665.11293121844.85507457544.82040144784.38916273133.88386049833.65167949283.52437925233.30302668273.161857168

NSTEMI5.21301170665.11293121844.85507457544.82040144784.38916273133.88386049833.65167949283.52437925233.30302668273.161857168

Rate1.40837431621.5798173431.61901492621.66336164481.88108054971.99892718051.96574529071.8215782021.70346819721.6621564467140.8374316151157.9817342996161.9014926189166.3361644812188.1080549702199.8927180472196.5745290674182.1578201987170.3468197209166.215644671

LCI1.35220287061.52064125841.56086561461.60496682091.81911335541.93507576131.90293711111.7615202361.64556610241.605054295135.2202870621152.0641258394156.0865614641160.4966820903181.9113355368193.5075761294190.2937111091176.1520236034164.5566102352160.5054295036

UCI1.46454576171.63899342761.67716423771.72175646871.9430477442.06277859972.02855347031.88163616791.76137029211.7192585984146.4545761681163.8993427598167.7164237736172.1756468722194.3047744037206.277859965202.8553470257188.163616794176.1370292067171.9258598383

Error Bars5.6171445535.91760846025.81493115485.8394823916.19671943346.38514191786.28081795836.00579659535.79020948575.7102151674

5.6171445535.91760846025.81493115485.8394823916.19671943346.38514191786.28081795836.00579659535.79020948575.7102151674

AGE-SEX ADJUSTED

Burden163148658299116133150168

All1999200020012002200320042005200620072008

Rate3.34761455763.50873188083.45388279783.35825082963.41114417083.26991164523.18170326732.98606578142.72470962152.6257593885334.7614557641350.873188083345.3882797807335.825082957341.1144170767326.9911645203318.170326727298.6065781366272.4709621547262.5759388457decline0.2156327011

LCI3.25585406423.41591473373.36556305193.27371451413.32623791833.18754700653.10142863662.90897723182.65151142222.5542803829325.5854064186341.5914733702336.5563051891327.3714514119332.6237918263318.754700653310.1428636594290.8977231796265.1511422168255.4280382883

UCI3.43937505113.6015490283.54220254373.4427871453.49605042333.35227628393.26197789793.06315433092.79790782092.697238394343.9375051095360.1549027958354.2202543723344.278714502349.6050423271335.2276283876326.1977897946306.3154330937279.7907820926269.7238394032

9.17604934549.28171471288.83197459168.4536315458.49062525048.23646386738.02746306767.70885495717.31981993797.1479005575

STEMI9.17604934549.28171471288.83197459168.4536315458.49062525048.23646386738.02746306767.70885495717.31981993797.1479005575

Rate1.48799129741.43899926031.34291051241.29507584621.06324852590.81912634750.75075697490.70137600210.60797375980.5591894994148.7991297447143.8999260278134.291051237129.5075846199106.324852590181.912634746475.075697493270.137600205360.797375983755.9189499394

LCI1.42713365841.37995350491.28801236681.2426018961.01589508680.77789915950.71176341690.66402060680.57341172980.526203432142.7133658421137.9953504934128.8012366781124.2601896018101.589508682977.789915953971.176341685466.402060683557.341172978952.6203431982

UCI1.54884893651.49804501561.3978086581.34754979641.1106019650.86035353540.7897505330.73873139730.64253578990.5921755668154.8848936472149.8045015622139.7808657959134.7549796379111.060196497486.035353538978.97505330173.873139727164.253578988559.2175566805

6.08576390255.90457553445.48981455895.2473950184.73534390734.12271879253.89935580783.73553952183.45620300483.2986067411

NSTEMI6.08576390255.90457553445.48981455895.2473950184.73534390734.12271879253.89935580783.73553952183.45620300483.2986067411

Rate1.85962326022.06973262062.11097228542.06317498342.34789564492.45078529772.43094629232.28468977932.11673586172.0665698891185.9623260194206.9732620552211.0972285437206.3174983371234.7895644866245.0785297739243.0946292338228.4689779313211.673586171206.6569889064

LCI1.79094767551.99811822552.04178723551.99689622972.27742065982.3794813522.36077850232.21725670942.05221111862.0031572121179.0947675513199.8118225513204.1787235537199.6896229744227.7420659784237.9481351989236.0778502301221.7256709362205.2211118616200.315721214

UCI1.92829884492.14134701562.18015733532.1294537372.41837062992.52208924352.50111408242.35212284932.18126060482.129982566192.8298844874214.134701559218.0157335337212.9453736998241.8370629948252.2089243489250.1114082374235.2122849264218.1260604803212.9982565988

6.8675584687.16143950396.918504996.62787536277.04749850827.1303945757.01677900366.74330699516.45247430936.3412676924

Incident6.8675584687.16143950396.918504996.62787536277.04749850827.1303945757.01677900366.74330699516.45247430936.3412676924

All

Rate2.73770714982.87001515172.794333272.7612845672.79217872632.68062821152.56615514782.38270621662.18998388892.0845866646273.7707149768287.0015151655279.4333270003276.1284567018279.2178726307268.0628211507256.6155147841238.2706216596218.9983888943208.458666459

LCI2.65573022742.78703090282.71570680952.68527029612.71598997652.60655474122.49444585612.31415509042.12461127382.0211079907265.5730227384278.7030902788271.5706809523268.5270296075271.5989976539260.6554741233249.4445856084231.4155090401212.4611273784202.1107990717

UCI2.81968407222.95299940052.87295973052.8372988382.86836747612.75470168182.63786443962.45125734282.25535650412.1480653385281.9684072152295.2999400522287.2959730483283.7298837962286.8367476076275.470168178263.7864439599245.1257342792225.5356504103214.8065338462

8.19769223848.29842488677.8626460487.60142709437.61887497687.40734702747.17092917576.85511261956.5372615166.3478673873

STEMI8.19769223848.29842488677.8626460487.60142709437.61887497687.40734702747.17092917576.85511261956.5372615166.3478673873

Rate1.32552159241.26833919211.19720014551.16580095370.96804845140.74761304530.66650427680.62677432890.55016527470.5023153045132.552159238126.8339192138119.7200145469116.580095366396.804845143374.761304528366.650427681762.677432886955.016527465350.2315304458

LCI1.26824544751.21305210911.14547174051.11603434440.92280726410.70812402340.62960943980.59127535170.51709378670.4708531781126.8245447479121.3052109067114.5471740472111.603434442392.280726408470.812402344462.960943979659.127535174151.709378668847.0853178088

UCI1.38279773731.32362627521.24892855051.21556756291.01328963880.78710206710.70339911380.6622733060.58323676260.5337774308138.2797737282132.3626275209124.8928550465121.5567562904101.328963878178.710206712270.339911383866.227330599758.323676261753.3777430827

5.72761449025.52870830715.17284049974.9766609244.52411873483.94890218393.68948370213.54989771283.30714879643.146212637

NSTEMI5.72761449025.52870830715.17284049974.9766609244.52411873483.94890218393.68948370213.54989771283.30714879643.146212637

Rate1.54788478961.72350547131.72851141171.71021512321.93266246282.02496377361.98160796611.83107580151.70530838471.6524079786154.7884789612172.350547134172.8511411731171.0215123158193.2662462824202.4963773569198.1607966138183.1075801505170.5308384734165.2407978591

LCI1.48559664331.65839784051.66609897541.64998587761.86884154981.96018542151.91823057991.77066927631.64733825211.5956399255148.5596643258165.8397840479166.6098975366164.998587761186.8841549817196.0185421489191.8230579876177.066927633164.7338252061159.5639925475

UCI1.6101729361.78861310221.79092384811.77044436871.99648337582.08974212562.04498535241.89148232671.76327851741.7091760317161.0172935965178.86131022179.0923848095177.0444368707199.6483375831208.974212565204.4985352401189.148232668176.3278517407170.9176031706

6.22881463546.51076308616.24124363646.02292455496.38209130076.47783520816.33773862636.04065251755.79701326735.6768053115

6.22881463546.51076308616.24124363646.02292455496.38209130076.47783520816.33773862636.04065251755.79701326735.6768053115

Total Mis With 411, 413, 414

1999200020012002200320042005200620072008

Incidence314.281331.53319.765311.213304.365290.59284.778264.1247.204241.711

Lower CI305.919322.99311.624303.257296.515282.925277.253256.902240.261234.86

Upper CI322.643340.07327.905319.168312.215298.255292.393271.298254.146248.563

Error Bars8.3628.548.1417.9567.857.6657.5257.1986.9436.851

8.3628.548.147.9557.857.6657.6157.1986.9426.852

NSTEMIs with 411, 413, 414Don't have

1999200020012002200320042005200620072008

Incidence186.951208.983205.769198.845211.836218.002221.067204.064194.666194.423

Lower CI180.498202.199199.235192.482205.285211.361214.435197.735188.503188.277

Upper CI193.405215.768212.303205.208218.388224.643227.7210.393200.828200.57

Error Bars6.4536.7846.5346.3636.5516.6416.6326.3296.1636.146

6.4546.7856.5346.3636.5526.6416.6336.3296.1626.147

Total Mis with Enzyme + UA

1999200020012002200320042005200620072008

Incidence297.402310.351303.174297.58292.8280.168274.586253.525235.19225.576

Lower CI289.268302.087295.247289.8285.101272.641267.196246.472228.418218.956

Upper CI305.537318.614311.101305.36300.5287.694281.975260.578241.962232.195

Error Bars8.1348.2647.9277.787.6997.5277.397.0536.7726.62

8.1358.2637.9277.787.77.5267.3897.0536.7726.619

NSTEMIs with Enzyme + UA

1999200020012002200320042005200620072008

Incidence170.085187.822189.19185.22200.275207.581210.876193.491182.653178.291

Lower CI163.929181.389182.924179.078193.904201.1204.298187.328176.684172.405

Upper CI176.241194.254195.455191.361206.646214.061217.354199.654188.623184.178

Error Bars6.1566.4336.2666.1426.3716.4816.5786.1635.9695.886

6.1566.4326.2656.1416.3716.486.4786.1635.975.887

Total Mis No Exit , Age-Adjusted

1999200020012002200320042005200620072008

Person years1018259.331639894.81

N3390362638253992416040524058380237023631

Incidence330.639331.09330.191323.009318.316296.334285.995256.297237.868221.417

Lower CI319.489320.215319.581312.816308.444287.017277.051248.045230.145214.223

Upper CI341.789341.965340.8333.203328.188305.65294.94264.548245.591228.611

Error Bars11.1510.87510.6110.1939.8729.3178.9448.2527.7237.194

11.1510.87510.60910.1949.8729.3168.9458.2517.7237.194

STEMI No Exit Age Adjusted

1999200020012002200320042005200620072008

Person years

N

Incidence150.418138.389132.627129.995104.36177.398968.526863.969755.769549.6373

Lower CI142.891131.352125.897123.52298.70372.636264.143659.843452.026746.2283

Upper CI157.946145.427139.357136.468110.0282.165372.910168.095959.512453.0464

Error Bars7.5277.0376.736.4735.6584.76274.38324.12633.74283.409

7.5287.0386.736.4735.6594.76644.38334.12623.74293.4091

NSTEMI No Exit Age Adjusted

1999200020012002200320042005200620072008

Person years

N

Incidence180.221192.701197.564193.015213.954218.935217.469192.327182.098171.779

Lower CI171.983184.398189.352185.13205.857210.924209.666185.177175.339165.441

Upper CI188.459201.003205.775200.9222.052226.945225.271199.477188.857178.117

Error Bars8.2388.3038.2127.8858.0978.0117.8037.156.7596.338

8.2388.3028.2117.8858.0988.017.8027.156.7596.338

Total Mis No Entry, No Exit Age Adjusted

1999200020012002200320042005200620072008

Person years

N

Incidence479.082489.233482.269473.987487.443447.01435.359391.169361.511339.011

Lower CI462.285472.168465.181456.919470.01430.217418.75375.228346.099324.032

Upper CI495.879506.298499.357491.055504.876463.804452.068407.109376.923353.99

Error Bars16.79717.06517.08817.06817.43316.79316.60915.94115.41214.979

16.79717.06517.08817.06817.43316.79416.70915.9415.41214.979

STEMI No Entry, No Exit Age Adjusted

1999200020012002200320042005200620072008

Person years

N

Incidence210.261192.768185.676188.674152.829110.95694.971788.555781.035471.9166

Lower CI199.118182.04175.057177.89143.051102.57587.154380.959773.728365.0083

Upper CI221.404203.496196.295199.458162.607119.337102.78996.151788.342678.825

Error Bars11.14310.72810.61910.7849.7788.3817.81747.5967.30716.9083

11.14310.72810.61910.7849.7788.3817.81737.5967.30726.9084

NSTEMI No Entry, No Exit Age Adjusted

1999200020012002200320042005200620072008

Person years

N

Incidence268.821296.465296.593285.314334.614336.055340.387302.613280.475267.094

Lower CI256.225283.168283.18272.059320.158321.485325.606288.586266.895253.794

Upper CI281.416309.762310.006298.569349.069350.624355.168316.64294.056280.395

Error Bars12.59613.29713.41313.25514.45614.5714.78114.02713.5813.3

12.59513.29713.41313.25514.45514.56914.78114.02713.58113.301

Incidence with revision

8.20913312948.20913312945.4975111445.4975111446.0964939076.096493907

8.40574561618.40574561615.41363279015.41363279016.43032964756.4303296475

8.16484180028.16484180025.10531119185.10531119186.37184739756.3718473975

8.11955824038.11955824035.04394930565.04394930566.36284538716.3628453871

8.16764311668.16764311664.56445884264.56445884266.77319050046.7731905004

8.05248725788.05248725784.02988833854.02988833856.97155298456.9715529845

7.90295491127.90295491123.83911840243.83911840246.90781197066.9078119706

7.61583456067.61583456063.69166096043.69166096046.66127430816.6612743081

7.26969952297.26969952293.43548743533.43548743536.40671188956.4067118895

7.14925729527.14925729523.29923284733.29923284736.34247132386.3424713238

All MI

STEMI

NSTEMI

Year

Incident (per 100 000 person-years)

Crude Incidence of Any Myocardial Infarction by Year

Covariates Burden

7.43144309557.43144309555.21301170665.21301170665.6171445535.617144553

7.60828512197.60828512195.11293121845.11293121845.91760846025.9176084602

7.35089269237.35089269234.85507457544.85507457545.81493115485.8149311548

7.36774068427.36774068424.82040144784.82040144785.8394823915.839482391

7.39466579937.39466579934.38916273134.38916273136.19671943346.1967194334

7.29615415487.29615415483.88386049833.88386049836.38514191786.3851419178

7.10251085717.10251085713.65167949283.65167949286.28081795836.2808179583

6.81239503766.81239503763.52437925233.52437925236.00579659536.0057965953

6.52928973926.52928973923.30302668273.30302668275.79020948575.7902094857

6.38362620626.38362620623.1618571683.1618571685.71021516745.7102151674

All MI

STEMI

NSTEMI

Year

Incident (per 100 000 person-years)

Crude Incidence of First Myocardial Infarction by Year

Covariates Incident

Table 1. Characteristics of All Hospitalized Myocardial Infarctions, January 1999-December 2008

YearNumbers for Text

PTotal MI57466

1999200020012002200320042005200620072008Value*Total STEMI17873

N5211558659396100623160736047577153245184Total NSTEMI39593

Age (years ± SD)67 ± 1368 ± 1369 ± 1369 ± 1370 ± 1370 ± 1470 ± 1469 ± 1469 ± 1469 ± 14

Sex Differences in Cardiovascular Aging

1) Coronary Microvascular Dysfunction

2) Coronary Arterial Remodeling 3) Left Ventricular Remodeling

Gender differences in pressure overload

normal

Concentric hypertrophy

Pressure load Hypertension Aortic stenosis

Women?!

Men Adaptive remodeling thick walls, small ventricle better reversibility?

Maladaptive remodeling thin walls, dilatation!

Figure 3

Microvascular Dysfunction

LV Remodeling Diastolic and Systolic Dysfunction

Myocardial Ischemia

Genetic and Environmental Factors

Myocardial Fibrosis and Scar MINOCA HFpEF

Arrhythmias Sudden Death

Arteriolar Remodelling

WISE-CVD Continuation (HFpEF) R01 – PI CN Bairey Merz MD - Proposed cascade of events in coronary microvascular dysfunction-related MINOCA, INOCA, and HFpEF

Crea, Camici, Bairey Merz EHJ 12/13

Distribution of EF Among Men and Women With HF: 21% and 27% are

HFpEF, respectively

Vasan RS et al. J Am Coll Cardiol. 1999;33:1948-1955.

EF>41

Sex Differences in Cardiovascular Aging

1) Vascular Factors in Cognition: The Impact of Sex on Memory – Susan Bell, MBBS, MSCI, MACC

2) Cardiovascular Aging, Sex Differences and Eicosonoids – The Fountain of Youth? – Susan Cheng, MD, MPH, MMSc

3) Bridging the Sex Gap in Early Myocardial Infarction Mortality – Why Sex Matters – Nakela Cook, MD, MPH, FACC

Sex Differences in Cardiovascular Aging – �Cardiovascular Disease, Cognition and Health PolicySlide Number 2Sex Differences in Cardiovascular Aging Which May Lead to Improved Men’s HealthSlide Number 4Slide Number 5Slide Number 6Slide Number 7Slide Number 837,674 male VA patients – �47% non-obstructive CADSex Differences in Cardiovascular AgingSlide Number 11Slide Number 12Slide Number 13Female BM-MNCs were more beneficial than male cellsSlide Number 16Incidence of Myocardial InfarctionSex Differences in Cardiovascular AgingGender differences in pressure overloadSlide Number 20Distribution of EF Among Men and Women With HF: 21% and 27% are HFpEF, respectivelySex Differences in Cardiovascular Aging