Faculty PPT HTN CHL Students SP2024 PDF

Faculty Key Notes: HTN + Dyslipidemi a Holly Vali, DNP, MSc., APRN, FNP-BC NR607, LHSON Updated, February, 2024  Objectives  Upon completion the learner will be able to:  Describe the clinical consequences of HTN & Dyslipidemia  Identify antihypertens...

Faculty Key Notes: HTN + Dyslipidemi a Holly Vali, DNP, MSc., APRN, FNP-BC NR607, LHSON Updated, February, 2024  Objectives  Upon completion the learner will be able to:  Describe the clinical consequences of HTN & Dyslipidemia  Identify antihypertensive medications and HTN goals with compelling indications for use in patient w a variety of comorbid conditions  Analyze the measurement of BP and evaluate effective strategies to protect the fidelity of this clinical assessment  Identify and discuss HTN guidelines alongside potential disparities in HTN outcomes 2/2 race-based approaches  Identify dyslipidemia medications and ASCVD risk aligned with treatment goals  Analyze medication and therapeutic regimes for dyslipidemia  Review HF, anticoagulant and cardiovascular related therapies in the context of primary care  Identify agents and regimes used for anemias managed in primary care HTN As we age, PVR increases Sum of HR x SV is Cardiac Output and CO decreases with aging Elevated BP in the older adult is most often first noted as systolic HTN Treating HTN with EBP Tx goals minimizes risk for HTN target organ damage Target Organ Damage  Hypertension Defined  White coat hypertension is elevated blood pressure in the clinician’s office but normal blood pressure at home. Masked hypertension is the opposite- elevated blood pressure at home but normal blood pressure in the clinic.  While they do not carry the same risk as sustained hypertension, masked hypertension and white coat hypertension are associated with an increased risk of cardiac events and target organ damage as compared to normotensive individuals (Tientcheu et al 2016).  Measurement of BP  It is important to consider best practices to measure an accurate blood pressure, and a single elevated or normal reading does not rule in or rule out hypertension (2017 ACC/AHA Guidelines).  Measure a seated BP 2-3 times after five minutes of rest and average the values plus check a standing blood pressure. These blood pressures can be measured using an automated machine, new evidence revealing it is preferred over manual blood pressure readings (new debate- auscultatory vs automated).  Two Sides of the Debate: Manual blood pressure cuffs need to be calibrated, and the human interpretation of manual readings can introduce more error (Myers et al 2011). However, not all automated machines are created equal, and more expensive does not mean better. The fidelity of an automated machine can be checked at validateBP.org.   BP Measurement: Is a Skill  Covers 80% of upper arm; cuff’s bladder ~40% of arm circumference  Too Small = Falsely HIGH reading  Avoid caffeine, smoking, exercising within 30 minutes  No talking during reading  Home BP Monitoring  Automated blood pressure machines make at home patient monitoring easier via intermittent self measurements or a 24 hour ambulatory BP monitor (which automatically checks a patient’s BP every 15-30 minutes over a 24 hour period). Home blood pressure measurements are more closely related to left ventricular mass than in-clinic measurements (Schwartz et al 2020 and Rader et al 2019). There now are CPT codes for interpretation for out of office BP readings (99473 and 99474 Berg 2019).  When interpreting home measurements for medication titration, be aware home BP readings are lower than office readings (2017 ACC/AHA Guidelines ). Another advantage of ambulatory 24 hour blood pressure monitoring is that nighttime readings are more accessible, and nocturnal BP readings have stronger prediction of cardiovascular events (Kario et al 2020). Accurate at home readings are likely to become increasingly more important with the continued prevalence of telemedicine.  Wrist Cuffs  Wrist and upper arm blood pressures are different; using intra-arterial sequential measurement in the same individual radial systolic BP is 5.5 mm Hg higher than brachial systolic BP with >20% of individuals having a difference of >10 mm Hg ( Armstrong et al 2019).  Currently, there is no validation procedure to translate radial blood pressure to brachial blood pressure, and at home measurement using wrist BP cuff can be unreliable ( Casiglia et al 2016).  Choosing a Target for Treatment  The first step of treating hypertension is choosing a blood pressure target. For most patients, including high cardiovascular risk patients, that target should maximizing a single medication.  ~50% of max dose/drug wo response- add another agent!  Two medications with varied MOA has a greater impact on lowering the BP  Maxing out on single meds can lead to more SEs wo achieving BP goal  Diuretics HCTZ commonly 1st line and well tolerated Inhibits sodium and chloride reabsorption in the distal convoluted tubule resulting in low volume low volume sodium depletion- alongside K+, and Mg+ leading to decreased PVR. Chlorthalidone (Thiazide-Like) is useful when HCTZ isn’t yielding goal - it is more potent and has a longer half life. Monitor K+ closely especially w initiation. Same properties but lacking the benzothiadiazide molecular structure. https://pubmed.ncbi.nlm.nih.gov/34739197/ Lasix isn’t 1st line as an anti-HTN diuretic for patients that have intact renal function. Can be used to tag onto HR with resistant LLE. Red Flags 2/2 overdiuresis: Postural Loops when 20 QD Contraindicated in CrCl amlodipine) All CCBs are modest negative inotropes – thus reduces Red Flags: CTN in HF, renal or hepatic impairment contractility of the heart. 2/2 MOA; negative inotropes lending to reduction in contractility of the heart  Beta adrenergic antagonists Think (lol): Atenolol, metoprolol, carvedilol, labetalol, bisoprolol, propranolol Block ẞ-1 (cardioselective) adrenergic receptor sites, blunting catecholamine response- resulting in decreased cardiac output and sympathetic outflow -commonly used for post MI pts Block ẞ-1, ẞ-2, α-1 are more effective in lowering BP: Carvedilol, labetalol : decreasing HR, SV & PVR- *Non cardioselective(ẞ-1&2) : propranolol, nadolol- avoid in asthma, copd, pulmonary lung dz, and PAD -commonly used for essential Red Flags: Sinus bradycardia, depression, HF tremor, situational anxiety, migraine decompensated, AVOID abrupt cessation, non prophylaxis cardioselective agents (ẞ-2 –lungs)- avoid w COPD, asthma.. Note: α-1 is relatively insulin sensitizing- others might increase glucose levels (consider with DM pts..)  Aldosterone Antagonist Think (one): Spironolactone, eplerenone Good for HTN resistance or primary aldosteronism Patho- Too much aldosterone = hypokalemia risk; not always an early sign.. Rx Considerations: Less aldosterone = hyperkalemia risk Spironolactone: Higher dose (150-300mg), androgen blocking effect. Eplerenone: Aldosterone Red Flags: hyperkalemia, gynecomastia, lower libido and ED antagonist wo anti-estrogen risk effect 25mg/d  Primary Aldosteronism  Resistant HTN 150/100 on to 3Rx; Controlled 3 drinks/day and/or alcohol withdrawal = elevated BP  OSA, Renal parenchymal dz, Primary aldosteronism, Renal artery stenosis (renal artery angioplasty is helpful).  Poor BP measurement  White Coat HTN or Masked HTN Algorithms For White Coat & Masked HTN  EBP in HTN Management Target Treatment Monitor Trends Validate BP Measurement Etiology of HTN Response to Rx: Resistant? Office BP Lifestyle Modifications Medication Adherence Home BP Nutrition Health Literacy Ambulatory BP Exercise Nocturnal HTN White Coat Vs Masked Comorbidities Orthostasis Risk Personalized Rx CTN: Implicit Bias in Race-Based Guidelines Previous studies demonstrated variances in response rates/Rx class. Unfortunately lending to the tendency/risk of delayed Rx of ACEi/ARBs- limiting cardio-renal protection Holt et al., 2022 Class Discussion  Hyperlipidemia/Dyslipidemia: Objectives  Upon completion the learner will be able to:  Identify the recommendations for dyslipidemia  Describe the classifications of dyslipidemia + treatment goals  Analyze the ASCVD risk factors pertaining to dyslipidemia management regimes  Evaluate the treatment regimens for dyslipidemia  Dyslipidemia 1. Dyslipidemia: umbrella term for lipid disorders e.g. familial hypercholesterolemia, hypertriglyceridemia, mixed hypercholesterolemia, diabetic dyslipidemia 2. ASCVD = atherosclerotic cardiovascular disease (defined as coronary death or nonfatal myocardial infarction, or fatal or nonfatal stroke) 3. Identify primary Issue: Is it elevated LDL? Or insulin resistance with high triglycerides and low HDL? Or both (aka “mixed hypercholesterolemia”)? 4. “Diabetic dyslipidemia”: insulin resistance, elevated triglycerides (TG) and low HDL 5. Homozygous familial hypercholesterolemia (HoFH): Rare, severely elevated LDL in adults and children. If unchecked, corary disease at young age e.g. 20 years old 6. Heterozygous familial hypercholesterolemia (HeFH): More common, elevated LDL in adults and children  Familial Hypercholesterolemia Types FH HoFH FH HeFH  1 in 250 000  1 in 250  LDL-C severely high in presentation  LDL-C is less severe in presentation, >190mg/dl in adults, >10mg/dl in  LDL-C >400mg/dl (total-C children >600mg/dl)  For Peds- an elevated LDL is > or =  EARLY identification is lifesaving 130 mg/dl  Dyslipidemia: Screening 1. Lp a (Low Density Lipoprotein): Strongly transmitted in families and is associated with early familial coronary disease. Lowered by Niaspan and PCSK9 inhibitors. Aggressive lowering of LDL also lowers risk from Lp (a). Risk factors of elevated Lp a 2. Apo B (Apoliprotein): Attached to every particle of LDL, giving a sense of LDL particle number and concentration. High Apo B means small, dense, and atherogenic LDL particles. 1. Consider checking in high risk patients who appear to be at LDL goal. 2. If Apo B remains elevated, then you need to lower LDL further. 3. Screening: Check total cholesterol, LDL, HDL, triglycerides and calculation of non- HDL cholesterol. 1. Fasting preferred if patient has hypertriglyceridemia. No need for routine Lp(a), or Apo B. 4. Guide to Screening: Start age 20 years old (minimum) then check every 5 years. If family history of CVD then check before 20 years old.  Dyslipidemia Primary Risk Factors Secondary Risk Factors  Genetic predisposition  Medications- beta blockers, OCPs  Heterozygous familial  Concurrent Conditions- DM, hypercholesterolemia pregnancy  Homozygous familial hypercholesterolemia  Diet high in saturated fats  Inherit defective genes that lead to  Sedentary lifestyle abnormalities in CHL synthesis or  Alcohol breakdown  Obesity  Smoking  HMG-CoA Reductase Inhibitors: Statins  Action: primarily block the conversion of HMG-CoA to mevalonate, which is the rate-limiting step in the production of cholesterol in the liver.  Maximum effects: usually are seen after 4 to 6 weeks of therapy. For this reason, dosage adjustments should not be made more frequently than q 4 weeks.  Contraindications: pregnant and lactating women, active liver disease, unexplained elevated aminotransferase levels, and heavy alcohol use.  Adverse events: Well tolerated by most patients; myopathies, gastrointestinal (GI) complaints, headache may occur  Interactions: Drugs that can also cause myopathy (e.g., cyclosporine, erythromycin, azole antifungals); grapefruit juice  Statin Myopathy  Statin myopathy: About 10-15% get muscle aches. If present, stop drug for 2-3 weeks, then trial same drug or at least 3 different drugs before casting the statin aside.  7 Drugs in Statin class: Guidelines\UMHS_Statin_Dose_Intensity_and_Equivalency_Chart.pdf (also located in WorldClass content)  Consider every other day dosing with atorvastatin and rosuvastatin (long acting statins).  Consider changing classes  More than 50% of cases of statin induced rhabdomyolysis were due to drug interactions  Clarithromycin is a CYP450 3A4 inhibitor +combine w either: atorvastatin, simvastatin, or lovastatin (3A4 substrates) = 10 fold increase in AUC- akin to drug toxicity and Rhabdomyolysis risk https://drug-interactions.medicine.iu.e du/MainTable.aspx So which statin here is LEAST likely to have a drug interaction? And which statins Diltiazem is a 3A4 inhibitor would be less likely to Grapefruit juice is a 3A4 pose an interaction inhibitor risk? * Atorvastatin & Rosuvastatin have longer half lives and higher bioavailability  Association Vs. Causal ..\jamainternal_mansi_2021_oi_210057_1638550210.45155.pdf  KEY POINTS:  Emphasis on diet & lifestyle modifications to AVOID T2DM progression  Risk Benefit Ratio  Statin + Ezetimibe (Zetia ®)  Ezetimibe: Can further lower LDL by about 17% on top of statin therapy.  MOA: Selective cholesterol absorption inhibitor- Decreases CHL absorption in the intestine  Anticipated LDL-C reduction 15-20% (helpful adjunct)  Well tolerated, no drug to drug interactions no renal/hepatic dysfunction  Drug Combo: Simvastatin + Ezetimibe = Vytorin®  IMPROVE-IT Trial: RCT, sample size n=18k, Ezetimibe plus statin versus statin plus placebo. Cardiovascular events lowered in ezetimibe plus statin group (average LDL of 53mg/dl) versus high dose statin alone (70mg/dl).  https://www.youtube.com/watch?v=cdqlpSFSF0U (Quick Take Video on IMPROVE- IT Trial)  IMPROVE-IT Trial ClinicalTrials.gov number  http://clinicaltrials.gov/show/NCT00202878  PCSK9  LDL cholesterol is normally cleared from the circulation as apoprotein B100 on the surface of LDL binds to LDL receptors on hepatic and extrahepatic tissues. LDL bound to its receptors undergoes a process of endocytosis.  Those with reduced PCSK9 activity, whether due to genetic polymorphism or administration of monoclonal antibodies to PCSK9, have lower cholesterol levels and a reduced risk of cardiovascular disease  INJ only, $$$$  CHL Pharmacology  Lipid Lowering Agents (19min)  PCSK9i  PCSK9: Human monoclonal Ab proprotein convertase involved in degradation of LDL receptors in liver.  All meds w –mab suffix, evolocumab (Repatha®), alirocumab (Praluent®)  Excess cholesterol in our body is primarily swept away by receptors on our liver cells, but a protein called “PCSK9” blocks this action by destroying the receptors on the liver cells causing the cholesterol levels to go up.  PCSK9 inhibitors attach to this protein and block their action. As a result, more receptors can continue to do their job and this lowers the amount of LDL CHL in the blood.  Additional LDL-C ~60% for patients already on an optimized stating therapy  Blocking activity of PCSK9 with monoclonal antibodies reduces the degradation of LDL receptors and increases clearance of LDL cholesterol.  FOURIER Trial: Statins alone versus statins plus PCSK9 inhibitor (baseline median LDL 92 decreased to a median LDL 30mg/dl). No decrease in CV death over 2.2 years, but 1.5% absolute risk reduction in composite CV events (acute coronary syndrome, stroke, revascularization).  GLAGOV Trial: PCSK9 inhibitor added to statin achieved 0.95% coronary plaque regression by intravascular ultrasound.  Bempedoic acid (Nexletol ®)  Adenosine Triphosphate-Citrate Lyase (ACL) Inhibitors (newly approved in 2020).  Indication: Heterozygous familial hyperlipidemia or established ASCVD risk wo goal, max statin tolerated statin therapy  MOA: ACL enzyme upstream of HMG CoA reductase in CHL synthesis- Inhibition of ACL reduces CHL biosynthesis in the liver and decreases LDL  Anticipated LDL-C reduction 18% (helpful adjunct)  Drug Combo: bempedoic acid + ezetimibe (Nexlizet) = LDL reduction of 38% when used maximally w statin  No Data for use during pregnancy  ADE Risk: Monitor uric acid levels /gout flare + tendon rupture risk (older, tendon damage history, concurrent or recent use of FQ).  Homozygous Familial Hypercholesterolemia  Rare and characterized as dysfunctional LDL CHL receptors on the liver- leading to severely elevated LDL levels, >600mg/dl  Rx includes specialized training and consultation (Juxtapid) and (Kynamro)  PCSK9i+ max statin + ezetimibe  Adding bile acid resins is tough as all medications are taken 1 hour prior or 4 hours after to ensure absorption  Limited data on statin + niacin benefits  Fibrates  Fibrates (Gemfibrozil, fenofibrate): Mainly lower TG, mild increase to HDL.  MOA: Unclear stimulation of lipoprotein lipase, enhancing breakdown of VLDL to LDL CHL  Multiple studies (per guidelines) have shown that if TG >500 and low HDL, despite dietary modifications then addition of fibrate to statin may trend toward less CVD events.  Overall, efficacy of use is limited  Contraindicated in pts with ho cholecystitis, cholelithiasis, and hepatic/renal dz  When used w statins, higher increase of myopathy reported  No studies in pregnant women  Other Non-Statin Rx 1. Niacin: Lowers TG and Lp (a). ~Poorly tolerated. 2. Bile Acid Resins: TG indicated >300mg/dl fasting, heavy routine adherence burden 3. Fish oil: Need at least 4gm daily to lower TG Over-the-counter preps have only 400-500 mg versus 1,000mg per capsule Rx strength. No proven benefit on CV outcomes.  Interactive ASCVD  Download MdCalc  ASCVD Risk Algorithm & Save to favorites  Case 1: History of ASCVD: (yes); Age 55: RESULT  Case 2: History of ASCVD: (no); LDL 200mg/dl: RESULT  Case 3: History of ASCVD: (no); LDL 160mg/dl; 45yrs; No diabetes; female; Total CHL 210; HDL 30mg/dl; BP 130/90 on ARB; non- smoker; BA: RESULT Mitigating High Risks:  Lipid Mgt Points Lifestyle changes are the cornerstone and foundation of cardiovascular prevention and should never be neglected in our conversations with patients. “Primordial prevention” is key! A patient’s risk of plaque burden is not only from the magnitude of LDL elevation but duration of exposure In primary prevention, the new ASCVD risk categories include low risk (< 5%), borderline risk (5 to