Hypertension Care and Cardiovascular Risk Reduction

like starting off with this particular slide because it explains the development of atherosclerotic cardiovascular disease.

Remember a few things sort of, why are you sitting here?

Why are you interested in cardiovascular disease?

Anybody?

What's that?

Because I, because everybody has it.

And guess what, if you're an average person, there's nothing wrong with being average, but you're gonna die of heart disease because that's the law of averages.

It gets everybody, it's an equal opportunity player, but it hits some people early because developing atherosclerotic cardiovascular disease is part of the normal aging process.

I don't wanna scare anybody, but it's just the three.

And a lot of people have cardiovascular risk factors and diseases that we manage.

But what is this whole development of atherosclerotic cardiovascular disease?

First, let's start off what, what our arteries are supposed to look like.

That's the picture on the top left.

So we have a cross section of an artery.

We have a bunch of arteries throughout our body and we have blood that actually travels through the middle.

And we're born with very patent and very healthy arteries.

We have, um, different linings, the tunica inma, which is the inner lining.

Then we have the middle lining, which is the tunica media and the tunica externa.

But a lot happens in the Tunica media, which develops into atherosclerotic cardiovascular disease.

The four steps of developing atherosclerotic cardiovascular disease, which are things like heart attacks, strokes, PAD, clogging of the arteries, which causes the deaths.

Heart failure causes a whole bunch of things to happen.

Starts off with what's called endothelial dysfunction.

That's step one.

And what causes endothelial dysfunction?

Cardiovascular risk factors like higher blood pressure hyperglycemia.

Smoking high cholesterol causes the inner cell lining the tunica inma to become dysfunctional.

And it allows leaking, the cell lining gets leaky and it can turn into the second step, which is fat streak development.

So fat streaks develop in that tunica media lining where we have fat deposition.

That's not good.

Why is it not good?

'cause it can lead to step three.

Step three is actually that the fat streaks turn into plaque.

And we've heard of plaque artery plaque and that's what causes occlusions and atherosclerotic cardiovascular disease.

Well, those fatty streaks actually elicit an inflammatory response.

And our body's way of combating inflammation is to attack it.

And the way it attacks it is in, in that lining causes the development of plaque.

And hopefully plaque just stays quiescent.

You have soft plaque.

And hard plaque starts off as soft.

When it turns into hard plaque, it gets calcified and it runs the risk of being unstable.

And that could lead to the fourth step in the development of atherosclerotic vascular disease, which actually is triggered by an unstable plaque.

Platelets get aggregated and it turns into an occlusion or thrombus.

And this is what can cause an acute myocardial infarction.

So this whole process is normal, but it's accelerated in patients with cardiovascular risk.

And look at the top players are, it's not just inflammation of lipids in those in the lining Of our arteries, it's actually primarily because of atherogenic lipids, which are LDL cholesterol.

We can also refer to it as APO lipoprotein B or A-O-B-A-O-B is bad, LDL is bad.

They're all basically the same.

Every LDL particle that we have in our body, which we view as the bag cholesterol, is attached to an A OB.

So they're both sort of synonymous with each other, but that's what deposits itself into the artery lining and causes the inflammatory response and the development of plaque, which can become unstable and causes problems.

So it really shines a light towards the importance of controlling that bad cholesterol.

That LDL cholesterol or the A OB, you can think of it that way.

If we were in other parts of the world, they look at A OB, like we look at LDL cholesterol, we primarily look at LDL as the one that we target for cholesterol management.

So I sort talked about some of this already, but do remember the big gain is to decrease the risk of A-S-C-D-D, which are things like coronary disease, ischemic stroke, and peripheral arterial disease.

Because that's the development of atherosclerotic cardiovascular.

That's the clinical manifestations that cause morbidity and mortality.

And we know, I don't care what a tox cells tells us, I do not care what a vlog says.

If any information is shared that cholesterol is not important and doesn't cause heart disease, it is wrong.

It is proven beyond shadow of doubt that LDL cholesterol elevations and a lipoprotein B elevations are bad cholesterol elevations leads to heart disease.

There's a lot of disinformation out there.

But that is the truth.

And I don't say it because I believe it, I say it because evidence tells me that is true.

Not just one study, not just two studies, not just a dozen studies, not just 20 studies.

A multitude of studies say the same thing though.

I wish our patients could read studies because then they would ignore the idiots on TikTok or blogs or whatever who sometimes aren't medically trained to say that some of the misinformation that they do.

I'll get off my soapbox, but has anybody had that story where people say, I heard cholesterol's good for you and you know, it doesn't matter if my LDLs 200, I'm still, you know, my grandmother lived to be not hundred.

They, they get these ridiculously stupid things that people say.

People do have the choice of deter the declining therapy.

They always do, but they don't have the choice of telling us lies and us accepting them.

We do not to accept them.

They can believe them, but we can't, um, endorse them.

And this is a big one.

And the cholesterol myth, I, I'm still baffled why some people think that high cholesterol is not bad for you.

It is, but people have a choice and I can't help people who decline.

You know, it's fine.

Just go somewhere else.

Um, because here, here is the real deal.

Lots of information that the higher LDL, the higher risk of heart disease, there's gonna be outliers.

Some people may have high alial not have a heart disease problem, but in populations amongst the general people, that is absolutely the trend.

And we know also beyond Shadow a doubt that when we use drug therapy and even lifestyle therapy to lo, that lowers LDL cholesterol, that as people do realize a reduction in LDL, their heart disease risk goes down.

It is proven in so many studies that it does not need to be proven.

Again, we're to the point where, which combination of treatments are best in which to do the, the best job at lowering LDL and morning heart disease risk.

This sort of, um, bang for your buck is every about 40 milligram per deciliter drop in your LDL cholesterol is associated with about a 25% reduction in cardiovascular events.

That's the predictive relationship between LVL and cardiovascular events.

It's been seen in a multitude of studies when we collect them together.

That's o we CI want you to keep this kind of person in the forefront of your mind.

I'll revisit him way at the end end when we finished.

This person is, um, very affectionately named John Doe.

So John Doe what's the deal with this person?

He's a 47-year-old black man.

He has a history of hypertension, dyslipidemia, and chronic kidney disease.

He also has pre-diabetes.

This is adapted from a real patient from the practice I work in.

I work at the University of Colorado.

I work out of a family medicine clinic and I've been there for a long time.

So we see a lot of people that don't yet have established disease.

But when I look at his first line, do you have some concerns about his cardiovascular risk profile?

Oh yeah.

I mean, it's bad enough to have hypertension, but high cholesterol, I'll throw that in there.

Bad kidneys and pre-diabetes.

This could be a lot of patients that you see.

And it is unfortunate this person's not that old.

47 is not very old.

So, um, it, it's hitting him early.

What else do you know about him?

His father died of a heart attack at 50, so he, maybe he's got three more years to live or he looks like his dad.

I don't wanna be crass, but you know, I think sometimes people need to look at their first degree relatives as a predictor, what might potentially happen to them.

So, um, that's why we're looking at this person, his social history.

Um, there's some good in this person.

He, he's a former smoker, so he's a quitter in a good way.

He showed that he can commit to something that it improves his health.

So that's actually something to lean into and to look for Pope and maybe motivate this person based off of that.

He also lives in a very disadvantaged, uh, neighborhood in Denver.

We'll come back to that fact 'cause it is important right now he doesn't follow any specific diet.

He drinks about two to three alcoholic beverage in a day and doesn't exercise.

What do you think about that?

That both Is that good?

No.

What's not good about it?

No.

Well, pre-diabetes, no physical activity.

That's not good.

And throwing hypertension too.

So lifestyle, even though I'm a pharmacist, lifestyle is the corner of prevent cornerstone and prevention and treatment.

So that doesn't look very promising.

Um, and what do you about the alcohol you two, two or three things a day?

Maybe it's more, I don't know, it's self-admitted.

I don't know what the portion size, all that kind of thing.

So, um, not maybe something to to work off of.

He does have Medicaid in Colorado.

Uh, his medications are pretty simple.

One blood pressure drug called hydrochlorothiazide and one drug atorvastatin In a low dose.

So that, that's it.

Maybe we can do more or maybe that maybe that's controlling them or maybe not.

We can look at his values and tell us more.

Oh, I don't think so.

Blood pressure 142 over 88 and similar when he measures it at home.

Now some clinicians may say, okay, that's good.

If you come to the third day you realize that's not good.

That's actually above goal.

His heart rate A to BS a minute, his BMI is 29.7, so he's on the brink of being categorized as having obesity.

30 and higher would be obese.

So, you know, probably not surprising with the dyslipidemia, hypertension, and free diabetes status.

His fasting labs are listed down here.

If we focus on cholesterol.

So let's see, his total cholesterol is two 20.

It seems.

That seems a little high, but we don't go off in total cholesterols except for screening.

His HDL is 30, that's considered low.

Anything less than 40 in a man low.

And that is a major risk factor for heart disease.

'cause that's the good cholesterol is LDL, the bad one is 1 44.

I like everybody in the double digits if possible, especially those with cardiovascular risk.

And he's in the triple digits 144 and we'll talk a lot about that.

And his triglycerides are little elevated 300.

This is a for the palama.

Surprised you that he has pre-diabetes.

He's got that metabolic picture.

His A1C 6.3 that absolutely is prediabetes, is serum creatinine.

Yeah, he is got that.

Um, chronic kidney disease, it's stage or stage three, it's called G three A two.

So he is got decreased.

GFR means decreased filtration.

He also has some albuminuria with that.

A two categorization.

Uh, those are probably because of long-term hypertension burden and you may think, oh, this isn't gonna happen in a 47-year-old.

It does happen and it disproportionately happens in certain populations.

Black patients disproportionately have more burden of that for a variety of reasons that I cannot explain.

So this, this isn't out of the, the realm of possibility and this is based on a real patient.

So that that's our man.

And your mental picture, keep that mental picture.

This metabolic syndrome patient where there's a lot of targets that are not optimized, not just blood pressure but lipid management.

His kidneys are starting to decline and he has prediabetes, probably drinks too much.

Doesn't exercise.

I don't know what he's eating.

His triglycerides are high.

So probably I can, I can guess that something's not not optimal.

So I think we can help him a lot.

And hoping, my goal is the end of the day when you come back to this case, you'll identify a whole bunch of things specifically to do in this.Description text goes here

1. Statins and Beyond: Innovations in Dyslipidemia Therapy and Cardiovascular Risk Reduction

2. Learning Objectives

3. Hypercholesterolemia

4. Steps in the Development of Atherosclerotic Cardiovascular Disease (ASCVD)

5. Hyperlipidemia in the US

6. John Doe

7. Breaking Down your Lipid Panel

8. How is LDL-C Determined

9. Evolution of Dyslipidemia Guidelines

10. 2018 AHA/ACC/Multisociety Guideline

11. Prevailing Concept from CTT meta-analysis: Proportional reduction in Major Vascular Events vs. absolute LDL-C reduction

12. 2018 AHA/ACC/Multisociety Guideline

13. 2018 AHA/ACC/Multisociety Guideline

14. Secondary Prevention: Clinical ASCVD

15. 2018 AHA/ACC/Multisociety Guideline

16. Primary Prevention: LDL-C ≥190 mg/dL

17. Familial Hypercholesterolemia (FH)

18. 2018 AHA/ACC/Multisociety Guideline

19. Primary Prevention: Diabetes

20. 2018 AHA/ACC/Multisociety Guideline

21. AHA/ACC/Multisociety Cholesterol Guideline: Risk Enhancing Factors

22. Primary Prevention: Increased ASCVD Risk

23. 2022 ACC ECDP

24. LDL-C Lowering Pharmacotherapy

25. Statins

26. Statin Pharmacokinetics

27. Lipid-lowering Medications in Pregnancy/Lactation

28. Statin Therapy

29. Statin-Associated Side Effects: Statin-Associated Muscle Symptoms (SAMS)

30. NLA Scientific Statement on Statin Intolerance

31. NLA Scientific Statement on Statin Intolerance

32. The Nocebo Effect

33. SAMSON: N-of-1 Trial

34. NLA Statin Associated Muscle Symptoms (SAMS) Clinical Perspective

35. Potential Strategies for Managing SAMS

36. 2018 ACC-AHA Cholesterol Guideline: Statin Safety Recommendations

37. The Ugly Truth…

38. Intermittent Nondaily Statin Dosing

39. Considerations for Selecting Nonstatin Therapy

40. Ezetimibe

41. IMPROVE-IT

42. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)

43. Fully human monoclonal antibodies against PCSK9

44. FOURIER:  Evolocumab in Very High-Risk ASCVD

45. ODYSSEY OUTCOMES:  Alirocumab in Recent ACS

46. VESALIUS-CV (TIMI 66):  Late Breaker at the AHA Scientific Sessions

47. VESALIUS-CV (TIMI 66):  Late Breaker at the AHA Scientific Sessions

48. VESALIUS-CV (TIMI 66):  Late Breaker at the AHA Scientific Sessions

49. Small Interfering RNA Therapy

50. Inclisiran

51. Inclisiran:  Clinical Efficacy on Maximally Tolerated Statin

52. ORION 3

53. Bempedoic Acid: An ATP Citrate Lyase Inhibitor

54. Bempedoic Acid: Clinical Efficacy

55. CLEAR Outcomes Trial: Bempedoic Acid

56. Potential Barriers for Lack of LDL-C Control

57. Gaps in Clinical Related to Hypercholesterolemia

58. Statin Adherence Reduces CV Events Post-MI

59. LDL-C Control is Low among High/Very High Risk

60. LDL-C Monitoring for Patients on Therapy

61. Monitoring Response to Therapy Is Important

62. Will LDL-C be “unretired” as a quality measure?

63. New and Emerging Agents

64. Lerodalcibep: A Small Anti-PCSK9 Binding Protein

65. Enlicitide Decanoate:  An Oral Macrocyclic Peptide PCSK9 Inhibitor

66. Enlicitide Decanoate Phase 3 Studies: Late Breakers at the AHA Scientific Sessions

67. CORALreef Phase 3 Studies

68. PURSUIT Trial:  Laroprovstat, Novel Oral PCSK9 Inhibitor

69. AZURE Phase 3 Studies

70. Cholesteryl Ester Transfer  Protein (CETP) Inhibitors?

71. TANDEM Study: Obicetrapib With Ezetimibe

72. Obicetrapib Trials in ASCVD

73. 2022 ACC ECDP

74. 2021 ACC Expert Consensus Decision Pathway  (ECDP): Hypertriglyceridemia

75. Fibric Acid Derivatives

76. Fibrates: Role in Therapy

77. Omega-3 Fatty Acids (FA)

78. Omega-3 Fatty Acid Medications

79. AHA Science Advisory: Safety and Tolerability of Prescription Omega-3 Fatty Acid Products

80. Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT)

81. STRENGTH Trial:  Omega-3 Carboxylic Acids (EPA + DHA)

82. Differences Between Omega-3 Fatty Acids

83. Niacin: Role in Therapy

84. Targets for Triglyceride Lowering

85. Emerging Therapies: Hypertriglyceridemia

86. Antisense Oligonucleotide (ASO): Targeting ApoC-III

87. Olezarsen: An ApoC-III Inhibitor

88. Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome (BALANCE)

89. Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia (Essence-TIMI 73)

90. Plozasiran: An ApoC-III Inhibitor

91. Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk (PALISADE)

92. Zodasiran: An ANGPTL3 Inhibitor

93. Pegozafermin:  Fibroblast Growth Factor 21 (FGF21) Analog

94. Novel and Emerging Lp(a)-Lowering Therapies

95. What Is Lp(a)?

96. Lp(a) Is an Inherited, Independent,  and Causal Risk Factor for ASCVD

97. A Focused Update to the 2019 NLA  Scientific Statement Lp(a) in Clinical Practice

98. Lipid-Lowering Medications and Lp(a) Effect

99. Pelacarsen Trial: Results

100. Olpasiran Trial: Results

101. Ongoing CV Outcome Trials With Lp(a) Lowering

102. Peripheral Arterial Disease

103. PAD Overview

104. Clinical Subsets of Peripheral Arterial Disease (PAD)

105. Medical Therapy for PAD

106. 2024 AHA/ACC Peripheral Arterial Disease (PAD) Guideline

107. Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD)

108. Cilostazol

109. Chronic Coronary Disease

110. CCD: Principles of Treatment

111. CCD: Symptom Modifying Therapy

112. 2023 ACC/AHA Guidelines: Symptom Modifying

113. 2023 ACC/AHA Guidelines: Disease Modifying

114. 2023 ACC/AHA Guidelines: Disease Modifying

115. Colchicine Targets the Inflammasome

116. Colchicine (LoDoCo)

117. Colchicine for CV Event Lowering

118. 2023 ACC/AHA Guidelines: Disease Modifying

119. Revisiting John Doe…

120. Discussion

121.