Global Risk Prediction in the New Millenium
Myocardial infarction is now almost 100 years "old". The eradication of heart attacks and atherosclerosis may become achievable with ApoI-Milano infusion.

In the mean time we have to stick to statins and it appears that in high risk subjects, high dose statin therapy is warranted.

 
The PROVE-IT study shows, that lowering LDL to 2.0 mmol/l reduces events when compared to LDL lowering to 2.6 mmol/l.

This is however true for the highest risk individuals, e.g. those with high risk unstable coronary syndromes.
The GREACE study stems from a low risk population but looked at high risk subjects with known coronary artery disease.

Only 12% of usual care subjects had statins (2% had fibrates), which in part explaines the excellent results.

However, the reduction in mortality may be due to the additional effect of risk reduction, possibly achieved by quit smoking in the structured care cohort.
This slide shows the high impact of LDL lowering on prognosis for the most important trials in primary and secondary prevention of heart attacks.
Because of the threat of interactions of CYP450 metabolized medications.

Especially subjects taking several drugs (such as older patients) may benefit from low dose statin in combination with Ezetimibe.

However, we still avait long term outcome data with Ezetrol.

The new risk perception 2004 is the global one.
Early detection of subjects at risk for heart attacks is mandatory.

In 15%, CAD manifests itself first as sudden coronary death.

 In 60%, the first manifestation of CAD is an unstable coronary syndrome.
The new risk prediction algorithms, such as PROCAM, have a very high specificity in excluding high risk subjects.

However, sensitivity to detect subjects with future AMI is only 33%.

This unsatisfactory situation may be approached by atherosclerosis imaging.

Atherosclerosis imaging is the most promising tool to detect the high risk subject.

Furthermore, vascular disease as uncovered by ultrasound or computed tomography is quite likely a strong marker for future death of any cause, especially vascular and cancer death.
In this slide we show, that TPA is a strong prediction for vascular death.

TPA is a relatively fast and reproducibally obtained measure of the global plaque burden and cardiovascular risk.

It may replace IMT measurements, which are less helpful, in that they have poor interscan reproducibility, even with repositioning software (e.g. EUREKA).

Coronary calcifications are a very strong marker of coronary risk, vascular risk and global mortality.

Several studies have shown up to 2004, that coronary calcifications add incremental value over conventional risk charts.

The basic of medical decision theory is the Bayes theorem.

In this slide, Bayes probabilistics clearly show the strong additive value of posterior probabilities with positive and negative tests.

 
This slide further lends support to the idea, that plaques, whereever they are measured, have to be interpreted on top of the presence and extent of cardiovascular risk factors.

The same plaque amount (global plaque burden) is less dangerous in subjects with a controlled risk factor profile.

This has to do with the difference of risk assessed with both methods: plaques reflect lifetime-accumulated rsik, risk factor reflect actual risk for unstable plaques.
In this large study involving 2229 subjects with FU over more than 20 years, actually measured LDL was not as predictive for IMT as LDL measured 21 years ago.

This study gives a very good example for the mutual importance of plaque as risk factors, and risk factors as risk factors.

Both informations are helpful in further risk stratifying subjects, especially those at intermediate risk for vascular events.
In only 9 years of observation, the incidence of obesity in US states is rapidly increasing.
Unfortunately, obesity is not only a risk factor for vascular disease, but also for cancer incidence.

Here we approach the idea, that vascular risk factors are often also risk factors for cancer.

Thus, measuring risk factor for AMI measure to some extent also the risk for cancer.
But not only: vascular risk factors appear to be a marker for another epidemic, that is Alzheimer disease.

It appears from this study, that controlling vascular risk factors, such as hypertension and diabetes, may reduce the incidence for Alzheimer Disease.

Here we start to understand the importance of vascular risk factor control. Every subject with uncontrolled vascular risk factors, such as smoking cigarettes, having diabetes or hypertension, will not only suffer more vascular events, but also more cancer events and is more prone to Alzheimer disease.

This slide shows the interrelationship between vascular risk fractors and the risk for cancer and vascular dementia.

 
Now we also start to understand, why coronary calcium measures risk for death from any cause.

Each individual is exposed to behavioural and environmental contact with aggressive and harmful substances.

These substances may either cause vascular events, cancer or even Alzheimer disease. It is just a question of time, what comes first.

Detecting and maximally treating vascular risk factors will therefore keep away doctors from treating disease.
We know, that early risk reduction reduces later disability, risk for death and health care expenditures.

Primary prevention of vascular disease reduced the incidence of vascular events, but also reduces the risk for cancer and possibly Alzheimer Disease.

Maximum education, expenditures, and health care activities are to be delivered to the setting of primary patient care.

Only with that, we will achieve the goal to keep people healthy until their organism will die naturally, possibly after having reached 100 years.

Michel Romanens, 21.03.2004