HLD in Adults: the Good (HDL), the Bad (LDL), and the Ugly (ASCVD)

Case

Betty is a 55yo patient with history of T2NIDDM, HTN, HLD, and tobacco use disorder, presenting for a follow-up visit regarding HLD after recent lab work revealed a total cholesterol of 220 and LDL of 100. Her aunt also just had a heart attack, and Betty is very worried about having a heart attack now too since her aunt had been so healthy! Betty asks how she can lower her risk of atherosclerotic cardiovascular disease events (e.g., MI/ACS, TIA, Stroke, or PAD) in the future. 


Lifestyle Modifications

Dietary changes make a big difference! The United Kingdom Lipid Clinics Program study found that, with diet alone, 60% of subjects had a mean reduction in body weight of 1.8%, which was associated with 5-7% reductions in total cholesterol and LDL. 

A Mediterranean diet (typically high in fruits, vegetables, whole grains, beans, nuts, and seeds; olive oil as an important source of fat; low to moderate amounts of fish, poultry, and dairy products, and little red meat) may lead to a reduction in total cholesterol

General advice on dietary changes: 

  • INCREASE vegetables, fruits, legumes, nuts, whole grains, fish
  • REPLACE saturated fat with monounsaturated and polyunsaturated fats
  • DECREASE intake of cholesterol, sodium, and trans fats
  • DECREASE intake of processed meats, refined carbohydrates, and sweetened drinks

Exercise is also a key lifestyle intervention. The 2018 ACC/AHA Guideline on the Management of Blood Cholesterol recommends “3-4 sessions [of physical activity] per week, lasting on average 40 minutes per session and involving moderate-to vigorous-intensity physical activity.”

  • Remember that some physical activity is still better than none in adults that can’t meet the above requirement, which may still be beneficial in reducing ASCVD risk
  • Individual episodes of exercise do not need to be a certain length of time
  • Short episodes of exercise are thought to be as beneficial as longer ones
  • Start at lower levels of exercise and then advance in intensity
  • Decrease sedentary behavior

Smoking Cessation

A 2011 study in the American Heart Journal looked at the effects of smoking cessation on lipoproteins.

  • Study details: 1-year, prospective, double-blind, randomized, placebo-controlled clinical trial
  • Findings: Despite weight gain, smoking cessation led to
    • Improved HDL-C, total HDL, and large HDL particles
    • No effect on LDL or LDL size
  • Conclusion: Increases in HDL may mediate part of reduced cardiovascular disease risk seen after smoking cessation

Back to the Case…

Betty thanks you for that helpful information regarding lifestyle modifications. She agrees to incorporate more of the Mediterranean Diet into her daily food intake, to moderately exercise for at least 150 mins total each week. You and Betty have established a great rapport, and she tells you that she is very hesitant to quit smoking. She asks you how helpful smoking cessation can actually be towards lowering her future cardiovascular risk…


ASCVD Risk

Clinical atherosclerotic cardiovascular disease (ASCVD) has several forms across 4 major areas: 

  • Coronary heart disease manifested by myocardial infarction (MI), angina pectoris, and/or heart failure
  • Cerebrovascular disease manifested by stroke and transient ischemic attack
  • Peripheral artery disease manifested by intermittent claudication and critical limb ischemia
  • Aortic atherosclerosis and thoracic or abdominal aortic aneurysm

There are 4 risk categories for ASCVD: 

  • Low (<5%)
  • Borderline (5-7.4%)
  • Intermediate (7.5-20%)
  • High (>20%)

There are multiple ASCVD risk calculators, including the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equations CV Risk Calculator, which measures 10-year ASCVD risk and can be used for patients aged 40-79yo. 

  • An individual patient’s ASCVD risk can vary significantly over time. A person’s ASCVD risk can be positively or negatively influenced depending on the development or treatment of concurrent medical conditions as well as lifestyle choices. As such, risk factors and an estimation of ASCVD risk should be regularly reassessed over time.

Back to the Case…

Betty thanks you for showing her the huge predicted decrease in risk if she were to quit smoking, and Betty is convinced and motivated to quit smoking! She tells you that her best friend just started taking a baby aspirin (ASA). Should she start taking a baby ASA too?


Low-Dose Aspirin

For decades, low-dose ASA (typically 81 mg/day) has been widely administered for ASCVD prevention. ASA is well established for secondary prevention of ASCVD and is widely recommended for this indication, but recent studies have suggested avoiding its use in primary prevention of ASCVD due to lack of net benefit. The 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease made the following recommendations: 

  • Low-dose ASA might be considered for primary prevention of ASCVD in select higher ASCVD adults aged 40-70yo who are not at increased bleeding risk
  • Low-dose ASA should not be administered on a routine basis for primary prevention of ASCVD among adults >70yo years
  • Low-dose ASA should not be administered for primary prevention among adults at any age who are at increased bleeding risk

In October 2021, the USPSTF released a draft statement on the use of ASA in primary prevention of ASCVD: 

 


Back to the Case…

Betty understands that since she is at high risk of for cardiovascular events over the next 10 years and since she is within the 40-59 yo age group, she should be taking a low-dose daily ASA. You confirm that she is not at an increased bleeding risk, and she agrees to start taking ASA 81 mg daily. She asks you if she should be on any other medications for her high cholesterol at this time?  If so, which one?


Statins!

Use is determined by patient’s baseline risk and underlying comorbidities.

  • Assess response to treatment 4-12 weeks after statin initiation or dose adjustment, repeated every 3-12 months afterwards as needed
  • Responses to lifestyle modifications and statin therapy defined by percentage reduction in LDL-C levels compared to baseline
    • In general, statins decrease LDL 20-60%, increase HDL 5-10%, and decrease TAG 10-33%
  • There is no need to check baseline LFTs and CK in the general population upon statin initiation. 
    • Exception: Check baseline LFTs in patients with liver disease

Indications for statin use per the 2018 ACC/AHA Guideline on the Management of Blood Cholesterol:

  1. Clinical ASCVD
    • Start high-intensity statin if age <75yo; moderate-intensity if >75yo
  2. LDL-C ≥190 mg/dL
    • Start maximally-tolerated statin
  3. Age 40-75yo with DM and LDL-C ≥70 mg/dL
    • Start moderate-intensity statin; consider high-intensity in presence of multiple ASCVD risk factors
  4. General adult who doesn’t meet above criteria
    • Consider starting moderate-intensity statin if ASCVD risk 7.5-20%; consider high-intensity if ASCVD risk ≥20%
    • If risk status is uncertain, consider using coronary artery calcium (CAC) scoring to improve specificity

Moderate- vs high-intensity statins: 

Risk-enhancing factors include:

  • Family history of premature ASCVD 
  • Persistently elevated LDL-C levels ≥160 mg/dL
  • Metabolic syndrome
  • CKD
  • History of preeclampsia or premature menopause
  • Chronic inflammatory disorders
  • High-risk ethnic groups (i.e., South Asian)
  • Persistent elevations of triglycerides ≥175 mg/dL

Coronary Artery Calcium (CAC)

CAC scanning detects calcium deposits in the coronary arteries. When ASCVD risk is uncertain or if statin therapy is problematic, it can be helpful to measure CAC to refine risk assessment. A CAC score predicts ASCVD events in a graded fashion and is independent of other risk factors, such as age, sex, and ethnicity.

  • If CAC is zero, treatment with statin therapy may be withheld or delayed, except in patients with tobacco use disorder, diabetes mellitus, and those with a strong family history of premature ASCVD.
  • A CAC score of 1 to 99 favors statin therapy, especially in patients ≥55yo.
  • For any patient, if the CAC score is ≥100 or ≥75th percentile, statin therapy is indicated unless otherwise deferred by the outcome of clinician-patient risk discussion.


Back to the Case…

Betty agrees to start taking Atorvastatin 40 mg once daily at bedtime. She thinks that her best friend was also on a statin, and had some bad side effects so she stopped taking it. What side effects should Betty be looking out for?


Statin Intolerance

Statin-associated adverse muscle events are a common concern (although evidence is mixed), and there’s even a task force on it!

Troubleshooting: 

  • Lower dose of statin or transition to a different statin
  • Consider alternative dosing, such as once or twice weekly
  • Remember that most patients who are re-challenged after stopping will tolerate statins!

Risk factors for statin intolerance:

  • Impaired renal or hepatic function
  • ALT >3x upper limit of normal
  • Age >75yo
  • Asian ancestry
  • Taking other medications that affect statin metabolism

Consider checking CKD or LFTs during treatment if concerned for side effects; however, the risk of rhabdomyolysis appears to be <1/1000 and the risk of drug-induced liver injury appears to be <1/100,000.


Back to the Case…

Betty is very appreciative. She’ll be monitoring for increased muscle aches and pains while on the statin. She feels motivated to make some lifestyle modifications and to add these two new medications into her daily routine!


Blog post based on Med-Peds Forum talk by Ashley Nguyen, PGY3