If this is true, what am I worrying about? We would only need to stay on track on: diabetes, smoking, BP, cholesterol.
Is it because we are building plaque even on 80-90 LDL, so eventually (super late in life) we would get an obstruction?
I think in part it is an endothelial failure which requires intervention on the pathway of aging (IMO acetylation).
Ah - look closely, actually, It’s not diabetes, it’s blood glucose above 100, same for hypertension(above 120). Basically very few people are left out the way it’s classified here, I think.
Full study:
The interesting question, of course, is what proportion of people with optimally controlled of those biomarkers still have plaque.
I figure I’ll join in here with my personal journey and a few questions. Cardio health is a major concern of mine as I have both high Lp(a) and high and rapidly increasing CAC scores. I’d appreciate any feedback.
Personal History – Male, 67yo (2026), 180-lb, 6-ft tall:
~2018 - CAC test with ~30th percentile blockage (missing data)
2022 - CAC test=421 (75th percentile) …yuck
2022 - Stress test: no sign of ischemia. Started on Statin (Rosuvastatin 20mg/day)
2024 – Carotid artery ultrasound: Arteries were clear, no thickening. Ankle-brachial index test: Blood Pressure nearly identical between ankles and heart (minimal arterial blockage)
2025 – Bloodwork (Apr-2025)
• Glucose=102 (high), A1C=6.3% (high, pre-diabetic)
• Calcium=11.4 mg/dL (high)
• Cholesterol=145 mg/dL, HDL=58, Trig=108, LDL-C=67, Chol/HDLC=2.5
• Lp(a) = 122 nmol/L
• ApoB = 67 mg/dL
• CRP=0.22 mg/L
2025 – Started Ezetimibe (10mg/day)
2025 – CAC test=749 (Sep-2025) (78th percentile) … yuck
2025 – Noted to my Doc that my blood calcium always seemed high
• After many tests – Diagnosed with hyperparathyroidism
• Had Parathyroidectomy (Oct-2025) – Calcium levels dropped to normal range (9.3 mg/dL)
2026 – Stress Test (Jan-2026) negative for ischemia, Coronary CT = Moderate coronary atherosclerosis, CAC = 879 (81st percentile) … big yuck. Started Praluent PCSK9 (Jan-2026) at 75 mg/2-wk
2026 – Bloodwork (Feb-2026)
• Glucose = 116 mg/dL (high), A1C = 6.7% (high, pre-diabetic)
• Calcium = 9.3 mg/dL (normal range)
• AST=42 U/L (high)
• Lp(a) = 108 nmol/L (reduced, but still high)
• Cholesterol=85 mg/dL, HDL=64, Trig=76, LDL-C<10, Chol/HDLC=1.3, non-HDL Chol=21
• ApoB <20 mg/dL
• HS CRP=0.4 mg/L
2026 – Stopped taking Ezetimibe (Feb-2026) per cardiologist recommendation
Thoughts/Questions:
• I’m pleased with the reduction in my LDL-C and ApoB due to Praluent, Rosuvastatin and Ezetimibe (subsequently dropped per cardiologist). I’ve had no side effects from this combination.
• HS-CRP is in a good range
• Lp(a) is still a big concern. The Praluent reduced my Lp(a) by about 11%, and when Pelacarsen is available (early 2027) I’m hoping to reduce my Lp(a) significantly
• I will be getting bloodwork done shortly (May-2026) to see if dropping Ezetimibe had a noticeable negative effect and if so, I will restart it
• I’m concerned that despite all my efforts, my glucose/A1C remain in pre-diabetic range
• Should I restart Ezetimibe?
• Should I add Nattokinase to further support heart health? 10,000+ FU range?
• Should I drop Rosuvastatin (20mg) and add Pitavastatin (4mg) to mitigate any statin effect on glucose?
• What other options to reduce glucose/A1C?
Metformin, SGLT-2 inhibitors like jardiance, GLP1 agonists. At 6.7% Hba1c you are already diabetic, so you should qualify for all these meds.
You need bigger guns at 6.7% A1c
I agree with restarting Ezetimibe if ldl creeps back up.
Nattokinas me is nice, but your priority should be lowering that A1c.
I guess I should have noted that I’ve been on metformin (500mg, 2x per day) for quite a few years. I also dropped quite a bit of weight (35-lbs) when I first found out that I was pre-diabetic. I stay quite active and do moderate weight training. I’ve been bouncing around on my A1C, ranging from 6.0% up to 6.7% recently. Thanks for the feedback
Continue escalating treatment then. Your options are, in order of efficacy :
- SGLT-2 inhibitors
- Glimins like Imeglimin
- GLP1 agonists
You didn’t mention acarbose. You must be burning mostly carbs. It would be great if you could become a fat burner, but it’s very hard to do for most. At least stay away from wheat and sugar. Start slow with the acarbose.
I agree the flozins are great. Dapa (forxiga) is less trouble than Empag .
Any proof/study on this or just your N=1 experience?
I hadn’t heard the term “flozins” … had to look it up 
I tend to have a low carb diet. I deal with both gout and neuropathy so I do watch what I eat. I try to avoid all wheat products, white rice, potatoes, high-sugar and processed foods. I “try”, but there is always some in my diet. I guess I need to be even more proactive with this given this diabetes issue.
I’d wanted this to resolve itself … but dang … didn’t happen 
I’ll research all the suggestions, and talk to my Doc, to see what might the best path considering my other meds and supplements.
N=1 big time, I noticed it right away, then later did read it in studies and the reason why eludes me now. My recollection is that they just stated it and didn’t explain.
I still have a couple boxes of empag in the drawer. I can’t make it through the night and stop all the time to pee in the day. Not worth it. Dapag I don’t even notice.
Full paper:
Very-High-Prevalence-of-Nonoptimally-Controlled-Traditional-Risk-Factors-at-the-Onset-of.pdf (461.3 KB)
Note the risk factors they used, and how they all include people receiving treatment for those risk factors:
- Blood Pressure: Systolic ≥ 120 mm Hg, diastolic ≥ 80 mm Hg, OR use of BP-lowering medication.
- Cholesterol: Total cholesterol ≥ 200 mg/dL OR lipid-lowering treatment.
- Glucose: Fasting glucose ≥ 100 mg/dL, diagnosis of diabetes, OR glucose-lowering treatment.
Why? 3 reasons, according to AI:
- If a person is taking medication to manage their blood pressure or cholesterol, it indicates that they have a physiological predisposition or a clinical diagnosis that requires intervention.
- Cardiovascular disease is typically the result of decades of exposure to nonoptimal levels of blood pressure or cholesterol. A person who currently has a “normal” blood pressure reading because they are taking an antihypertensive drug has still likely experienced significant periods of high blood pressure in the past. The study aimed to capture the antecedent occurrence (what happened before the event), and a prescription is proof of that history.
- The study sought to determine if CVD truly occurs in “low-risk” individuals. In clinical practice, a person taking a statin is not considered “low risk” simply because their current LDL cholesterol is low; they are categorized as a patient with a managed risk factor. By including treatment in their definitions, the researchers ensured they weren’t misclassifying treated patients as “healthy” or “risk-factor-free.”
I don’t think there is any doubt that there are issues with high BP, high ApoB and/or high glucose. The question is what happens without those.
Sorry, I was not looking to answer your question, just my own curiosity about study parameters.
As for your question: all the paper says is that an analysis of those with 0 risk factors that still had a CVD event revealed that they either had multiple risk factors that were “high-normal” or “subthreshold” range, had genetic factors not accounted for, or non-traditional factors not accounted for (high inflammation, physical inactivity).
Physionic: Can we reverse Atherosclerosis?
Video and Summary/analysis here: Physionic Podcast Videos and Summaries / Transcripts - #120 by RapAdmin
I switched to it myself from Rosuvastatin three months ago and my A1C seemed to drop from 5.4 to 5.2 and working out at the gym has been more painless (probably was having myalgia without realizing it until I stopped Rosuvastatin)
Good data point. Thank you