Ethan Weiss: Preventing Cardiovascular Disease — the Latest in Imaging, Blood Pressure & Metabolic Health

Calcium Scoring and CT Angiograms

• Calcium score:
• Indicates the amount of calcium in the coronary arteries
• Correlated with adverse outcomes (more calcium = higher risk)
• Represents healed plaque
• Useful for understanding risk in certain populations
• Low radiation and low cost
• Useful in certain contexts, not for everyone (e.g., not for 25-year-olds)
• CT angiogram:
• Provides finer resolution than calcium scoring
• Can detect small calcifications and soft plaques that calcium scoring might miss
• Useful for longitudinal assessment and simultaneous CAC and CTA

Peter Atia’s Personal Experience with Calcium Scoring and CT Angiograms

• Had a calcium score of 6 in his mid-30s
• Despite this, no one took it seriously due to his overall health and lipid levels
• In 2016, had a CT angiogram and calcium score
• Calcium score was 0, but CT angiogram found a tiny speck of calcium in the proximal LAD
• Radiologist explained that small calcifications can be missed in calcium scoring
• In 2022, had another CT angiogram and calcium score
• Calcium score was 2, and CT angiogram was identical to the one in 2016
• Shows that the same lesion can have different calcium scores (6, 0, and 2 in this case)

Implications of Calcium Scoring and CT Angiograms

• 15% of people with a 0 calcium score have a finding on CTA (either a missed calcification or a soft plaque)

• Importance of considering both calcium scoring and CT angiograms for a more accurate assessment of cardiovascular risk
  CAC and CTA Scans in Cardiology

• Calcium scans (CAC) and CT angiograms (CTA) are both used in cardiology to assess heart health

• CAC scans are less expensive and more commonly covered by insurance, but provide less information than CTAs
• CTAs provide more detailed information about the heart and arteries, but are more expensive and less likely to be covered by insurance

CAC Scans

• CAC scans measure the amount of calcium in the coronary arteries
• Calcium buildup can indicate atherosclerosis (plaque buildup in the arteries)
• CAC scans are relatively inexpensive and often paid for out-​​of-​​pocket by patients
• Limitations: CAC scans may not provide enough information for younger patients or those with less obvious risk factors

CTA Scans

• CTA scans provide a more detailed view of the heart and arteries, including the presence of unstable plaques
• Can help identify relevant issues in patients with negative CAC scores
• More expensive than CAC scans and less likely to be covered by insurance
• In a world with universal coverage, CTAs would likely be the preferred method due to the additional information they provide

Insurance Coverage and Costs

• Insurance coverage for CAC and CTA scans varies depending on the carrier and the patient’s specific plan
• CAC scans are more likely to be covered by insurance, while CTAs are often paid for out-of-pocket
• The cost of a CTA can range from $700 to $3,000, depending on the patient’s insurance and negotiated rates

• Some doctors have developed strategies for navigating insurance coverage to obtain CTAs for their patients when necessary
  CTA FFR and Trials

• Fame and Fame Two trials

• Looked at FFR in angiography
• FFR: detect pressure gradient across stenosis
• Helps determine severity of blockage

• Supplements qualitative assessment of visually assessing lesions

• Interventional cardiology

• Used for patients with refractory symptoms

• Used in unstable emergency acute settings

• Stable angina patients

• Most interesting in contemporary practice

• Range of opinions on treatment

  • Stenting or revascularization
  • Medical therapy
  • Trial of medical therapy, then stenting if symptoms persist

• Courage trial

• Showed it’s okay to have plaque without intervention

• Stenting people without symptoms doesn’t offer benefit over optimal medical therapy
  High Calcium Burden in Patients

• Patients with high calcium burden (north of 1000) and no symptoms

  • No routine stress testing or CT angiogram
  • Focus on optimizing medicines
• High calcium score triggers a response, but not necessarily further testing

Fractional Flow Reserve (FFR) in Asymptomatic Patients

• FAME trial: more aggressive stenting strategy in asymptomatic patients with significant pressure drop 
  • Result: standard of care in cath labs
• CT-​​based version of FFR study 
  • Identifies people who might need intervention based on CTA
  • Algorithm predicts pressure drop
• No clear evidence of a group of asymptomatic people who would benefit from stenting beyond optimal medical therapy

Stenting in Asymptomatic Patients

• Opening a severely blocked artery should theoretically improve outcomes 
  • Possible explanations for lack of improvement: 
    • Elaborating plaque contents downstream
    • Playing “whack-​​a-​​mole” with multiple areas of disease
• Stenosis is a good predictor of future events, but not necessarily the plaques that would get stented

• Ischemic preconditioning and collateralization may help patients with high stenosis survive without symptoms
  Troponin and CK Elevations After Intervention

• Troponin or CK elevations can occur after a long intervention

  • Raises questions about creating a small myocardial infarction (MI) during stent placement
  • Possible downstream risks include arrhythmias or other issues later in life
• Observational data links area under the curve of troponin elevations post-​​PCI to outcomes 
  • More troponin elevation correlates with worse outcomes

Non-​​Invasive Adjuncts to CT Angiography

• Study (not yet published) found no difference in all-​​cause mortality or MACE 
  • Reduction in need for catheterization
• UCSF now uses CTFFR on most CTAs to reduce the number of people going to the lab 
  • Prevents unnecessary stents, but can be achieved without FFR

Fat Attenuation Index (FAI)

• A CTA bolt-​​on, similar to FFR 
  • Looks at characteristics of fat around the plaque
  • Possibly measures inflammation around the plaque

Elevated CAC in Athletes

• Some data suggests that athletes with high levels of cardiorespiratory fitness may have a higher frequency of coronary calcification 
  • Increased shear forces across the endothelial surface could lead to damage and calcification
  • Statins may increase calcification while lowering the risk of events
• Exercise may have a similar effect, but without the same level of evidence as statins 
  • More exercise is generally better for cardiovascular health, but more calcium is worse

Balancing Exercise and Calcification Risk

• The relationship between exercise and calcification risk is complex

  • More exercise may increase calcification, but also provides other health benefits
  • Determining the optimal balance of exercise and calcification risk is challenging
    Discussion on Statins and Calcium Scores

• Patients often question the significance of their calcium scores due to exercise

  • Doctors still treat high calcium scores as representative of plaques in arteries
  • Exercise is beneficial, but cannot guarantee a “free pass” on calcium scores
• Statins are widely prescribed, but some patients experience side effects 
  • Muscle side effects, transaminase elevations, especially when mixed with Zetia
  • Some patients avoid statins due to fear and misinformation
• Fear of statins may stem from skepticism around science and Big Pharma 
  • Conspiracy theories and documentaries demonize statins
  • Difficult for people to accept that pharma companies can do both good and bad things

Blood Pressure and Kidney Health

• Kidneys are sensitive to high blood pressure 
  • Tiny organ with high cardiac output
  • Sensitive to pressure, like the heart and brain
• Normalizing blood pressure is essential for long-​​term kidney, heart, and brain health
• Blood pressure is a significant risk factor, along with smoking and ApoB

Neglect of Kidney Health

• Both doctors agree on the neglect of kidney health and nephrology as a subspecialty

• Importance of maintaining kidney health for overall health and longevity
  Lecture on Hypertension

• Co-​​lecturer: Jean Olsen, a kidney pathologist

• Importance of the kidney in regulating blood pressure
• Single gene mutations can lead to extreme increases or decreases in blood pressure 
  • Most located in the proximal collecting duct in the tubule
• Blood pressure increases with each decade of life 
  • Is this normal aging or a function of pathology?

Blood Pressure Variation

• Blood pressure varies greatly throughout the day 
  • Changes during sleep, exercise, and stress
• Physiologically, blood pressure is meant to go up in certain situations
• Clinical trials help determine how to measure and manage blood pressure 
  • Example: Sprint trial (2014 or 2015) 
    • Faced pushback from those who believed it over-​​medicalized normal aging

Blood Pressure Management

• Aim to get patients as close to 120/​​80 as possible without causing harm 
  • Potential harms include side effects, impacts on lifestyle, and toxicity
• Evidence from clinical trials suggests that 120/​​80 is normal regardless of age 
  • Anything above that is considered abnormal
• Blood pressure increase with age is not considered a normal function of aging 
  • May be due to decreased kidney function or increased vascular stiffness

• Variation in blood pressure is normal, but it’s important to manage it based on clinical trial guidelines
  Measuring Blood Pressure Accurately

• Traditional method: measuring blood pressure in a quiet room with an automated cuff

  • Person seated and relaxed, blood pressure measured three times with five-​​minute breaks in between
  • Average of the three measurements is taken
• Real-​​life situations can cause higher blood pressure readings 
  • Stress, physical activity, etc.
• Importance of measuring blood pressure accurately and consistently 
  • Helps detect changes and potential health issues
  • Some people measure their blood pressure at home twice a day for at least two weeks once a year

Ambulatory Blood Pressure Monitoring

• 24-​​hour monitoring of blood pressure 
  • Cuff inflates and deflates periodically throughout the day
  • Provides a more accurate representation of blood pressure during various activities and sleep
  • Useful for detecting “white coat hypertension” or abnormal blood pressure during sleep

Future Blood Pressure Monitoring Devices

• Current wrist-​​based devices and other non-​​invasive methods have not been proven accurate
• Some attempts to use cell phone cameras to measure blood pressure, but not widely adopted

• No clear advancements on the horizon for accurate, wearable blood pressure monitoring devices
  Continuous Blood Pressure Monitoring

• Importance of continuous blood pressure monitoring

  • Glucose is less variable than blood pressure
  • Continuous ambulatory BP monitor would be a game changer in medicine
  • Important for heart, brain, and kidney health
• Current limitations in blood pressure monitoring technology 
  • No reliable continuous ambulatory BP monitors available
  • Existing devices have failed to provide accurate measurements
  • Opportunity for engineers to develop new technology

Sprint Trial

• Aimed to test a new hypothesis on aggressive management of hypertension 
  • Observational studies showed lower risk of bad outcomes with optimal blood pressure (120/​​80 or less)
  • Designed to evaluate whether treating people to different goals resulted in a change in outcomes
• Results
  • Significant difference in blood pressure between the two groups
  • Mortality benefit for getting closer to 120/​​80
  • Some risks, such as increased falls, syncope, and kidney dysfunction
  • Takeaway: Get as close to 120/​​80 target as possible without causing problems

All Hat Trial

• Tested five different classes of medications for hypertension 
  • Calcium channel blockers, ACE inhibitors, diuretics, beta blockers, and alpha agonists
  • Alpha and beta agonists discontinued due to harm
  • Result: Use any of the other three classes (calcium channel blockers, ACE inhibitors, diuretics) as first line in primary hypertension treatment
  • Similar outcomes for amlodipine, lisinopril, and thiazide

Blood Pressure Treatment Goals

• JNC guidelines
  • JNC 6: Normal BP was 120–130/80–85, hypertension >140/​​90
  • JNC 7: Normal BP <120/​​80, pre-​​hypertension 120–140, hypertension >140/​​90
  • JNC 8: Controversy led to discontinuation of guidelines

• U‑shaped curve in blood pressure treatment

  • Too low can also be harmful
  • Treating to below 120/​​80 may not be advantageous for everyone
  • Individualized approach based on patient’s needs and side effects
    Sprint and Step Trials

• Sprint and Step trials were stopped early due to overwhelming benefits

  • Some people argued to keep going, but the decision was made to stop and report results
  • Sprint trial results were likely not spurious, but real, robust, and repeatable
• Step trial included patients with type 2 diabetes, making it more representative

Blood Pressure Medications

• First priority is to get blood pressure under control 
  • Then optimize the combination of medications based on individual circumstances
• Different medications may be more suitable for different patient populations 
  • ACE inhibitors and ARBs may be more beneficial for those with kidney disease or diabetes
  • Calcium channel blockers like Amlodipine are easy to use and have few side effects
• Tolerability is important for medication compliance

Atherosclerosis Risk Factors

• Four major pillars of risk in ASCVD: 
  1. Smoking
  2. Hypertension
  3. ApoB
  4. Metabolic health
• Metabolic health is more complex and cannot be measured by a single number 
  • Focus on sources of fat outside of subcutaneous depots
  • Different people have different genetic capacities for storing fat

Fat Storage and Health Risks

• Humans have evolved to store energy in the form of fat 
  • Subcutaneous adipose tissue stores triglycerides
  • Different people have different capacities for fat storage
• When the “bathtub” of fat storage overflows, health risks increase 
  • Fat can accumulate in problematic areas, such as around the viscera, within muscles, in the pancreas, and around the heart
  • Even small amounts of overflow can have significant health consequences

• BMI is not a perfect measure of risk, but it can be useful in large populations

  • Overall adiposity is important, but the distribution of fat also plays a role in health risks
    Fat Storage and Metabolic Health

• Fat storage location affects health risks

  • Evolutionarily programmed to store energy in hips, butt, and legs
  • Storing fat in belly and organs is harmful and increases risk of diseases
• Genetic alleles predispose to differences in body composition and disease risk
• Lipodystrophies: rare genetic diseases where people cannot store fat properly 
  • Generalized lipodystrophy: inability to store fat at all
  • Selective lipodystrophy: inability to store fat in gluteal and leg regions 
    • Leads to an overabundance of fat in the abdomen and organs
    • Extremely high risk of metabolic disease and coronary artery disease
• Association between body shapes (apple vs. pear) and disease risk 
  • Still a major problem despite advances in risk reduction (e.g., blood pressure management, smoking cessation, lipid management)

Understanding Fat Storage and Metabolic Health

• Current understanding is low-resolution 
  • BMI, DEXA scans, and MRI provide limited information
• Questions to explore: 
  • Is visceral adipose tissue (VAT) bad because it’s not stored in the subcutaneous space, or is it doing something fundamentally different?
  • Are there cytokines from VAT cells that are different from those in other cells?
  • Can gluteal and leg fat storage capacity be changed to improve metabolic health?

• Potential targeted therapies for metabolic health

  • Experiment with human genetics as a guide
  • Test therapies in patients with lipodystrophy and eventually target other metabolic-​​associated diseases, including coronary disease
  • Fat mass ratio (ratio of upper body fat to lower body fat) may be an important factor in determining health risks
    Ethan Weiss on Lipodystrophy and Blood Pressure

• Lipodystrophy: a rare condition where the body is unable to store fat in the right places

  • Often goes undiagnosed due to lack of awareness among doctors
  • Diagnosis sometimes occurs by accident, e.g., when a doctor notices unusually lean and muscular legs
• Familial partial lipodystrophy (FPLD) 1, 2, 3, 4, etc. 
  • FPLD1 is the most common, but there is no agreed-​​upon way to diagnose it
• Lipodystrophy patients can help us understand more common versions of fat storage problems 
  • High fat-​​to-​​muscle ratio (FMR) can convey more risk than smoking for coronary disease events
• Importance of monitoring and treating high blood pressure 
  • Many people are unaware of their blood pressure levels
  • Even slightly elevated blood pressure can have significant consequences
  • Blood pressure treatment is a low-​​cost, high-​​impact public health measure