Why low ideal cardiovascular health & sub clinical disease

Over my lifetime there has been an avalanche of research into the pathophysiology of atherosclerotic cardiovascular disease.  As many of my previous blogs have indicated the precise mechanisms underlying the initiation and progression of cardiovascular disease are pretty clearly understood:

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The process of pathological ageing of our arterial vasculature begins with trapping (oxidised) atherogenic lipoproteins (LDL; IDL and VLDL) in the sub endothelial space of the artery.  Oxidative modification of the atherogenic lipoproteins sets up a cascade activation of the inflammatory and cytokine immune system to potentiate the progression and instability of the atherosclerotic plaque in the vascular wall.

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Plaque instability is governed by many factors but chiefly driven by activation of the thrombotic and inflammatory systems exacerbated by the hydrostatic forces (blood pressure tearing plaque) in the artery leading to progressive end organ damage which we can monitor clinically as:

  1. Endothelial dysfunction
  2. Sub clinical atherosclerosis (thickened irregular Intima-Media and plaque formation)
  3. Micro and macro protein leak though the glomerulo capillary network (micro and macro albuminuria)
  4. Increased vascular rigidity (loss of vascular compliance)
  5. Development of systemic hypertension
  6. Left ventricular hypertrophy (with loss of LV compliance)
  7. Presence of left ventricular diastolic dysfunction systolic dysfunction
  8. Vascular retinopathy
  9. Overt vascular disease
  10. Overt conductive system disease

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The mechanism by which OPTIMAL MEDICAL THERAPY (OMT) improves morbidity and mortality and can postpone clinical events can be demonstrated in this Intravascular Ultrasound (IVUS).  This is the typical graphic generated by an intravascular ultrasound guidewire down a major epicardial coronary artery (in this case the proximal left anterior descending coronary artery – LAD).  The “black dot” in the centre of the two pictures is the ultrasound guidewire in the lumen of the LAD with the eccentric plaque noted extending from 11 o’clock to 4 o’clock.  Although the plaque volume is similar in the two arteries the plaque on the left is a typical “stable” plaque verses the “unstable” plaque on the right graphic.  The stable plaque is generally seen in patients on OMT with little residual risk and is characterised by a thick fibrous capsule and very little intra plaque inflammatory content (low cytokines and inflammatory cells) whereas the right plaque has a very thin capsule separating the blood from the plaque content which has a high content of oxidised free atherogenic lipoproteins, cytokines and cells , increased thermal temperature all contributing to plaque instability.

Relevant to the two plaques above the people harbouring these vessels will both be asymptomatic as the lumen of the vessels are “wide open”; they would both have negative exercise stress tests and both individuals may be excellent athletes. But the plaque instability on the right will explain the sudden cardiovascular events in an otherwise asymptomatic individual.

These plaques typically rupture or fissure at the shoulder of the plaque exposing the inflammatory content of the plaque to the circulating blood causing immediate intravascular thrombosis and blockage of the artery.

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At LDL levels < 1.8 the average plaque regression is approximately 1-2% per 18 months with plaque stability usually clinically apparent after only 6 months of high dose potent Statin therapy.

The STENO -2 trial is a good example of aggressive multiple risk intervention in a high risk “healthy” Type 2 diabetic.

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Aggressive risk factor management with a combination of Statin therapy to keep LDL 1.8-2.5; HDL > 1.2; TG < 1.7; BP ~ 130/70; glucose control to HbA1c < 6.5%; low BMI and exercise:

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Typical for the OMT/ Statin trials the separation of the Kaplan Meyer curves occurs early around 6 months of therapy with progressive separation of the curves thereafter.  In this trial there were approximately 50% less hard clinical events on the intensive treatment arm verses conventional treatment at 8 years.

Many different classes of drugs that are used in optimal medical therapy in the prevention of cardiac disease and the management of patients with vascular disease are “anti-atherosclerotic”.

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So if we have all this information why the high rates of poor health and sub clinical vascular disease in otherwise “healthy people”?

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I believe rather that slating the theory of the mechanism and causes of cardiac disease, the real stumbling blocks to prevent and manage heart disease are contained in my graphic above.

Starting at the centre is the PATIENT for if we can’t motivate the patient to stick to the rules with lifestyle diet and exercise and compliance with all anti atherosclerotic therapy then we expect poor health and high levels of sub clinical disease.

At 12 o’clock is the role of the DOCTOR where I see the following problems:

  1. Failure to risk stratify accurately risk burden for vascular disease
  2. Failure to manage the “global” risk spending too much time on individual risk factors (silo approach)
  3. The is a general resistance to aggressive global risk reduction leaving healthy people with considerable “residual risk”
  4. There is a fear of using multiple anti-atherosclerotic poly pharmacy
  5. There is a misguided opinion that invasive interventions are better and safer than aggressive optimal medical therapy (to stabilise plaques)

The INTERNET is a “double-edged sword” as although valuable information is present this is embedded in some seriously flawed; incorrect and frankly misleading junk. The internet for instance is full of absolute rubbish posted by cholesterol and statin skeptics contributing to much unwarranted anguish amongst those who don’t have the truth at their finger tips. Careful scrutiny of the misleading data will show that the authors often have unsubstantiated supplements; books and magic wands to prevent and treat vascular disease. 

THIRD PARTY FUNDERS are at times mischievous and meddlesome and contrary to popular opinion they are not in business to save lives but rather to protect shareholders.  The limited “formularies” and poor adherence to current international guidelines (2012 European Society of Cardiology) obstruct and pose major limitations to achieve optimal medical outcomes.

Finally the supplement industry is a major source of unsubstantiated claims to prevent and treat cardiovascular disease.  We have a ton of evidence based medicine from conventional cardiology double blinded placebo controlled trials. The efficacy and safety of treatments involving massive number of patients treated with various anti-atherosclerotic drugs is without question.

A wonderful example of evidence based medicine is the 2012 meta analysis of ALL the cholesterol lowering trials in relatively low risk individuals.

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The results slide shows on the extreme left the 5 year calculated risk of a major vascular event (MVE) of the groups from low risk <5% to the very high risk >30% (one-in-three risk of an event over 5 years).  I have just selected two outcomes namely coronary revascularization and major vascular events comparison for these risk groups on Statin therapy.  For each 1,0 mmol/l LDL reduction for each risk group we see an approximate 20% risk reduction in events compared to placebo.  This data is incredibly robust and supports all our information to date from Statin trials demonstrating survival proportional to LDL lowering (4 mmol/l LDL reduction = approximately 80% risk reduction once LDL approaches 1.8 mmol/l).

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I truly believe we are at the stage of preventing atherosclerosis completely and in individuals with either sub clinical or clinical vascular disease we can effectively switch off the process.  This entails sticking to the algorithm above keeping:

  1. BMI < 25
  2. LDL < 1.8
  3. HDL > 1.2
  4. Non-HDL < 2.0
  5. BP < 130/80
  6. us-CRP < 1.0
  7. HbA1c < 6.5%
  8. and resting HR < 70

I see confirmation of this daily with true health free of sub clinical disease if the 8 boxes are ticked.

Proverbs 10:17

Whoever heeds discipline shows the way to life,but whoever ignores correction leads others astray.

Yours in health


3 thoughts on “Why low ideal cardiovascular health & sub clinical disease

  1. hi not sure how to contact you . was wondering about the omega three problem in the country and that it doesn’t have what the levels are. also, apparently they spoil easily. which product would you recommend, thanks

    • Hi Husain
      Yes the over the counter preparations of Salmon Oil from Dischem (“the real thing”) or from CLICKS (Salmon Oil) seem OK.

      Otherwise eat whole food oily fish like Salmon, Sardine or Pilchards.

      Regards Cardiologydoc

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