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Khurram Nasir: Can Earlier LDL-C Lowering Change the Trajectory of Cardiovascular Disease?
Khurram Nasir and Kausik K. Ray/LinkedIn
May 27, 2026, 17:14

Khurram Nasir: Can Earlier LDL-C Lowering Change the Trajectory of Cardiovascular Disease?

Khurram Nasir, Co-Director Houston Methodist-Rice University Digital Health Institute (HM-Rice DHI) at Houston Methodist, shared on LinkedIn:

“Can Earlier LDL-C Lowering Change the Trajectory of Cardiovascular Disease?

A thought-provoking simultaneous publication by Kausik Ray published in American Journal of Preventive Cardiology presented at European Atherosclerosis Society yesterday revisits one of the central questions in prevention:

Are we intervening too late?

Using data from 17 randomized lipid-lowering trials involving more than 105,000 participants, Karungi and colleagues examined how the relative cardiovascular benefit of LDL-C lowering changes across different baseline risk levels.

The findings are thought provoking.

  1. Contrary to the traditional assumption that lower-risk individuals derive only modest benefit, the investigators observed that relative risk reduction per 1 mmol/L LDL-C lowering was actually greater in lower-risk primary prevention populations.
  2. In trial populations with annualized event rates around 1% per year, each mmol/L LDL-C reduction was associated with roughly a 36% relative reduction in events, compared with approximately 13% in populations with event rates near 3% per year.

The paper bring to light an important conceptual framework.

  1. As atherosclerosis advances, larger LDL-C reductions may be required to achieve the same proportional benefit.
  2. In lower-risk and presumably earlier-stage disease, even modest LDL-C reductions may yield meaningful relative risk reduction.

This shifts the discussion from simply ‘who is high risk today?’ toward a broader life-course perspective

  1. Are we waiting long before intervening?
  2. Can modest but earlier LDL-C lowering alter cumulative vascular exposure before disease becomes biologically irreversible?
  3. Should early primary prevention become more central to our prevention frameworks?

I think the implications extend beyond statins alone.

For the future we need to think around long-duration therapies, , AI-guided risk prediction, imaging-guided prevention, and cumulative LDL exposure increasingly points toward a future where prevention may begin earlier, become more personalized, and focus more on preserving vascular health before advanced disease develops.

An important extension of the accompanying paper is the editorial by Roger Blumenthal and Alexander Razavi, which frames these findings through a simple but powerful analogy borrowed from Arnold Palmer:

‘Timing is everything in life and in golf.’

For decades, much of our prevention framework has focused on identifying individuals once short-term risk becomes sufficiently high.

What if we can address the cumulative exposure , then when we lower LDL-C may matter just as much as how much we lower it.

Importantly, the authors do not advocate indiscriminate pharmacotherapy.

Instead, they highlight a more personalized strategy integrating PREVENT risk estimation, inflammatory markers, lipoprotein(a), CKM risk factors, and importantly CAC imaging to identify those most likely to benefit from earlier intervention.

In many ways, the editorial captures an important philosophical shift. The future may not simply be about treating advanced disease more aggressively, but preserving vascular health before advanced atherosclerosis develops.

Timing, indeed, may be everything.

Also this news release.”

Title 1: Cardiovascular event rate modifies response to pharmacologic LDL-C lowering in primary prevention: implications of a systematic review and meta-analysis for clinical practice

Authors: Irene Karungi, Christophe A.T. Stevens, Julia Brandts, Kausik K Ray

Read the Full Article on American Journal of Preventive Cardiology

Khurram Nasir

Title 2: LDL-cholesterol lowering: timing is everything

Authors: Alexander C. Razavi, Roger S. Blumenthal

Read the Full Article on American Journal of Preventive Cardiology

Khurram Nasir

Stay updated on all scientific advances with Hemostasis Today.

Alexander C. Razavi American Journal of Preventive Cardiology Arnold Palmer Atherosclerosis Blood CAC Cardiology Cardiovascular Disease Christophe A.T. Stevens CKM CVD European Atherosclerosis Society Health Hematology Hemostasis News Hemostasis Today Irene Karungi Julia Brandts Kausik K. Ray Kausik Ray LDL Cholesterol LDL-C Lipoprotein(a) Medicine Roger S. Blumenthal thrombosis
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