Cardiometabolic Disorders In Midlife Women

Question 1

Cardiovascular Health (CVD)

Answer 1

-leading cause of death in women; more than all cancers, TB, HIV/AIDS, malaria combined
-mortality in women exceeded that in men from 1984-2013
-rates declining bc of medical advancement
-greater awareness that sxs, presentation, & disease are different in women
-1 in 3 women die from this

Question 2

Menopause & CVD Risk

Answer 2

-most CVD occurs after meno
-premature meno (natural or surgical) is a risk factor for CVD
-potential mechanisms linking meno & CVD risk after meno:
>incr total LDL-C
>higher prevalence of metabolic syndrome
>direct vascular effects of hormone changes
>HbA1c & BP maintain usual trajectories

Question 3

RFs for CVD

Answer 3

-Traditional: older age, DM, smoking, overweight/obesity, MetS, physical inactivity, HTN, HLD, fam hx of premature CVD
-Non-traditional: preterm delivery, premature meno, HTN in pregnancy, GDM, autoimmune disease (Lupus & RA), depression, breast ca tx
-HIGH RISK: established CHD, cerebrovascular disease, PAD, AAA, DM, CKD, 10yr predicted risk >10%

Question 4

Ideal CV health predictors

Answer 4

-total cholesterol <200mg/dl
-BP <120/80 mmHg
-fasting BG <100 mg/dl
-BMI <25 kg/m2
-no smoking
-moderate intensity physical activity >/=150 min/wk or vigorous >/=75 min/wk or a combo
-healthy diet

Question 5

Assessment of CVD risk

Answer 5

-2013 ACC/AHA guidelines recs for sex/ethnicity based risk tool
-calculator provides a 10yr lifetime risk for MI/stroke
-based on age, sex, ethnicity, cholesterol, BP, DM, smoking status

Question 6

CVD prevention

Answer 6

-smoking cessation
-dietary modification - Mediterranean or DASH, fruits/veggies/lean meats, restricted intake of sat fat, trans fat, sugar, sodium
-physical activity w resistance training for 20 min 2-3x/wk
-wt reduction: central obesity more dangerous than subq fat; goal BMI 18.5-24.9; goal wait <35in or <31.5 in for south Asian descent
-etoh should be limited to <1 drink/day

Question 7

CHD & HT

Answer 7

-HT started w/in 10yrs of meno or in women aged <60yo lowers all-cause mortality & dose not increase risk of coronary events
-may even reduce coronary events
-HT started later in meno or in older women incr risk of CHD

Question 8

Stroke & HT

Answer 8

-stroke risk not increased w HT in women aged <60yo or w/in 10yrs of meno
-HT may increase risk of stroke in women starting HT after 60yo
-transdermal estrogen or lower doses of oral estrogen may have a lower stroke risk

Question 9

VTE & HT

Answer 9

-increased risk of VTE w oral HT
-risk does not appear to be incr w transdermal estrogens and may be lower w lower dose of oral estrogen
-risk increases w age & BMI; x3 higher in obese
-micro progesterone less thrombogenic than progestins
-no risk w vaginal ET
-HT not recommended for primary or secondary prevention of CVD

Question 10

CVD Prevention - Aspirin

Answer 10

-undisputed benefit of aspirin for secondary prevention in women w established CVD; 81mg prevents recurrence of MI, TIA, & stroke
-lack of efficacy as primary prevention
-avoid in patients >70yo or those w high risk of bleeding
-considered as primary prevention in 40-69yo age group if high risk of CVD, low risk of bleeding, individualized shared decision making w patient

Question 11

ASCVD Risk Assess

Answer 11

-high-risk for future ASCVD events (MI/Stroke): women w clinical CVD, women w LDL-C >190, no need for further risk assess for therapy decisions
-for the rest, estimate 10y & lifetime risk: <5% low risk, 5-7.4% borderline risk, 7.5-19.9% intermediate risk, >20% high risk
-hx of multiple major ASCVD events or one major event & multiple high-risk conditions

Question 12

Major ASCVD events

Answer 12

-hx of MI
-recent ACS
-ischemic stroke
-symptomatic PAD

Question 13

High-risk conditions for ASCVD events

Answer 13

-age >65yo
-DM, HTN, smoking, CKD, heterozygous familial hyper cholesterolemia, prior coronary artery bypass grafting or percutaneous coronary intervention, heart failure, persistently elevated LDL-C despite max tolerated statin therapy & ezetimibe

Question 14

HTN

Answer 14

-one of the greatest RF for CVD
-1 in 3 deaths in women in US
-prevalence incr w aging in both sexes but more so in women after 60yo (75% of women will have it by this age); bump right around meno by 4-5 mmHg in SBP; cause of postmeno incr in BP w estrogen withdrawal, wt gain, neurohumoral factors, salt sensitivity

Question 15

HTN Management

Answer 15

-risk-based tx algorithm from ACC/AHA
-lower targets for BP than JNC 8 guidelines (goal <130/80)
-thresholds for tx: >140/90 if no clinical CVD or 10yr ASCVD risk <10%; >130/80 if clinical CVD, DM, CKD, HF, or 10yr ASCVD risk >10T%
-no sex-specific tx recs; meds AE worse in women
-some professional societies recs higher BP goal <150/90 for pts aged >60yo

Question 16

Anti-HTN Guidance

Answer 16

-4 classes of agents for initial therapy:
>thiazide diuretics
>CCBs
>ACEIs
>ARBs
-choice of drug dictated by comorbidities
>gout: avoid thiazides
>HF w reduced EF: avoid CCBs
>bilateral renal artery stenosis: avoid ACEIs & ARBs
>thiazides & CCBs preferred as mono therapy in blacks
>chlorthalidone is preferred thiazide (longer duration of action, reduced CVD risk)

Question 17

HLD

Answer 17

-trigs & cholesterol-rich apolipoprotein B (apo B) containing lipoproteins (LDL-C & non-HDL-C) are important RFs for ASCVD
-level of apo B lipoproteins incr rapidly in the first year after meno
-incr in apo B lipoproteins later in meno correlates w age-related changes

Question 18

HLD Management

Answer 18

-based on rinsed ACC/AHA 2018 guidelines
-goal of tx: lower risk for future ASCVD events, not to target specific LDL-C goals
-heart-healthy lifestyle measures are the foundation of management & risk reduction at all ages:
>should be rec to all pts
>dietary pattern emphasis on fruits, veggies, whole grains, low-fat dairy, poultry, fish, legumes, nuts, nontropical veggie oils
-5-6% calories from sat fat
>avoid trans fat
>reg physical activity
>maintain ideal body wt

Question 19

High-intensity Statin therapy

Answer 19

-based on ASCVD score
-high-intensity statin therapy (wo calculating ASCVD) is recs for clinical ascvd (goal LDL-C reduction >50%);
-for very-high-risk score, consider adding nonstatin therapy to max tolerated statin if LDL-C >70;
-severe hypercholesterolemia (LDL-C >190)

Question 20

Moderate-intensity Statin therapy

Answer 20

-40-75yo w DM and LDL-C >70 to <190mg/dl and 10yr ASCVD risk >7.5%; if ASCVD >20%, initiate statin, if <20%, consider risk-enhancing factors that favor statin (fam hx of premature ASCVD, HTN in pregnancy, CKD, MetS, chronic inflammatory conditions)
-consider measuring coronary artery calcium (CAC) to aid decision-making if risk status uncertain (statin therapy if CAC >100 or 75th percentile
-may be considered in pts 40-75yo wo DM, LDL-C >70 to <190 and 10yo ASCVD risk between 5-7.5% if several risk enhancing factors present

Question 21

No statin therapy

Answer 21

-40-75yo wo DM, LDL-C >70, total cholesterol <190, 10yr ASCVD risk <5%
-follow up
>assess adherence & LDL-C response w repeat lipid panel 4-12 was after statin initiation/dose adjustment
>if LDL-C reduction is less than expected (30-50% for moderate-dose statins & >50% for high-intensity statin or if further LDL-C reduction needed -lifestyle adherence reinforcement, incr statin dose/intensity, repeat lipid panel q3-12mo PRN

Question 22

AEs to statin-therapy

Answer 22

-myalgia (creative kinase normal) - pain, stiffness, cramping, weakness; 5-10% prevalence in clinic; incre predisposition w higher age, female, low BMI, high risk meds, comorbidities, Asian, etoh use, high levels of physical activity, trauma
-true statin intolerance (myositis & rhabdo) is rare
-most patients can tolerate moderate dose therapy (challenge your patient)
-modest incr in risk of DM (pts w pre-existing predispo for DM); onset 2-4mo earlier, clinical significance of statin-induced DM is unclear
-no incr in liver toxicity (routine LFTs not needed)

Question 23

Sex-specific Guidelines for Statins

Answer 23

-no female specific guidelines
-studies for benefits in women use is needed

Question 24

Non-statin Therapy

Answer 24

-option for very high-risk pts who are on max statin
-consider ezetimibe or PCSK9 inhibitor (reduce CV events when added to background statin therapy)

Question 25

Triglycerides

Answer 25

-elevated triglyceride-rich atherogenic apo B lipoproteins as incr CV risk
-mainstay of tx for modestly elevated TG (<500mg/dl) —> lifestyle modification & statin therapy
-severe elevation in TGs (>500mg/dl) usually secondary to oral estrogen, high-fat diet, poorly controlled DM; —> tx low-fat diet, tx underlying condition, TG-lowering therapy (fenofibrate, gemfibrozil, high-dose omega-3 fatty acids); gemfibrozil is contraindicated in statin therapy
-TG >1000mg/dl; often d/t monogentic disorder, maybe a/w incr risk of pancreatitis

Question 26

Metabolic Syndrome (MetS)

Answer 26

-state of insulin resistance
-underlying causes: overweight/obesity, physical inactivity, genetic factors
-increased risk for: DM, nonalcoholic steatohepatitis, sub clinical atherosclerosis, CVD
-postmeno are increased risk
-dx criteria is the presence of >3 of these:
>central obesity (>35in or 88cm wait circ, 31.5in for South Asian)
>elevated serum TG >150mg/dl
>low serum HDL-C <50mg/dl
>elevated BP >130/85mmHG
>fasting plasma glucose >110mg/dl
-50-85% of postmeno have at least one feature of MetS
-rates vary on basis of ethnicity & socioeconomic status

Question 27

Type 1 Diabetes

Answer 27

-aka latent autoimmune diabetes of the adult
-autoimmune disease, immune-mediate destruction of beta cells
-classically a Peds disease, but 83% of type 1DM are adults: immune-mediate w late onset, after age 20; positive abs of antiglutamic acid decarboxylase & zinc transpoerter (differentiates from type 2)
-a/w other autoimmune like celiac & hashimoto
-bc of incr life expectancy, many older women have type 1 DM; greater risk for hypoglycemia, osteoporosis, dementia, CVD
-postmeno have greater risk of MetS; higher risk of CVD w concurrent type 1 DM

Question 28

Prediabetes

Answer 28

-risk for development of DM; 31% of US women have this but only 14% are dx’d
-dx’d if FBG 100-125mgdl, Ha1c 5.7-6.4%, or 2hr BG during OGTT 140-199mg/do
-etiology from combo genetic & environmental (lifestyle); fundamental defects are beta cell dysfunction & insulin resistance

Question 29

Type 2 DM

Answer 29

-nearly 12% of all women have type 2 DM
-25% >65yo have type 2 DM
-prevalence rates according to ethnicity:
>American Indians 15.3%
>Black 13.2%
>Hispanic 11.7%
>Asian 7.3%
>Non-Hispanic white 6.8%
-same etiology as preDM

Question 30

Screening for PreDM & Type 2 DM

Answer 30

-fasting glucose, HbA1c, OGTT (uncommon)
-single test sufficient for PreDM; type 2 records a second confirmatory test
-screen all women beginning at age 45yo (repeat q3yr); test earlier if RF present:
>BMI >25% (23% in Asian)
>first-degree relative w DM
>high-risk ethnicities (American Indian, Black, Hispanic, Asian)
>hx of CVD
>HTN
>HDL-C <35 or TG >250
>women w PCOS
>physical inactivity
-yearly testing for preDM+
-women w GDM test at least q3y after birth
-normal screening: retest at least q3y, more frequent if high-risk

Question 31

Prevention of Dm

Answer 31

-lifestyle
-metformin (effective in younger women, less useful in postmeno)
-pioglitazone (not commonly used bc of AEs

Question 32

Menopause & Risk of DM

Answer 32

-hormone changes of meno increase central obesity (incr chance of MetS & type 2 DM)
-aging also as wt gain & central Abe’s its (incr insulin resistance)
-HT attenuates the abdominal fat accumulation in postmeno (reduced risk of type 2 DM w HT use, HT should be based on standard guidelines, HT should not be used to reduce risk of MetS or slow progression of DM)

Question 33

Management of DM: Lifestyle

Answer 33

-foundation of DM tax
-encourage lifelong changes in diet habits
-diet patterns like DASH & Mediterranean preferred (lowers BP, lipids, CVD risk)
-physical activity reduces insulin resistance (walking 30min/d, start slow & increase)
-individualized programs preferred based on age, comorbidities, preferences
-multidisciplinary team-based approach for lifestyle improvement has greater success
-limit etch intake (<1 drink/day)
-smoking cessation

Question 34

Pharmacotherapy for Type 1 DM

Answer 34

-tight glycemic control reduces the risk of micro vascular complications bc of DM (retinopathy, nephropathy, neuropathy)
-balance w risk of hypoglycemia
-older women prone to hypoglycemia (dangerous if w cognitive impairment)
-HbA1c targets should be lowered in older women d/t hypoglycemia
-consider using insulin analogs w lower predisposition for hypoglycemia in select patients (deluded - like glargine)
-some may prefer insulin pump therapy (outcomes not superior to multiple daily inj)
-CGM may also lower risk of hypoglycemia
-artificial pancreas (in development, hybrid closed-loop system, uses sensor data to adjust basal insulin delivery rate

Question 35

Pharmacotherapy for Type 2 DM

Answer 35

-Based on the guidelines from ADA & AACE
-no sex-specific guidelines
-based on efficacy, cost, AES, wt change, hypoglycemic risk
-cost is crucial bc some need more than 1 agent for tx
-intent is glycemic control while avoiding wt gain & hypoglycemia
-metformin 1st-line therapy bc of efficacy, wt neutrality, safety, reasonable cost
-2nd-line guided by comorbidities & individual circumstances: women w known CVD use liraglutide & empagliflozin or cangliflozin (reduce CV & mortality); women wo known CVD use sulfonylureas, insulin (hypoglycemia & wt gain), DPP-4/SGLT-2 I/ GLP-1 RA do not cause hypoglycemia or wt gain
-in woman w higher HbA1c, dual agents or insulin may be needed
-individualize goals: based on age, life expectancy, hypoglycemia risk, & risk/benefit of tight glycemic control; reduces risk of microvascular damage & macrovascular complications at the expense of increased hypoglycemic risk; older women w limited life expectancy should have higher Ha1c

Question 36

CV Risk Reduction in Women w DM

Answer 36

-based on guidelines, not sex-specific
-statin therapy recs; moderate-intensity for 40-75yo w diabetes & LDL-C >70mg/dl
-consider aspirin therapy in 40-70 yo w diabetes & 10y ASCVD >10%
-antihypertensive therapy goal <130/80
(ACEI, ARBS reduce nephropathy)
-women w diabetes & known CVD: antihyperglycemic meds that reduce CVD risk is recommended (empagliflozin, canagliflozin, liraglutide, semaglutide)