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Macrovascular Residual Risk THROUGH LANDMARK STUDY

4 March 2010
PROCAM: Assessing cardiovascular risk: relevance of atherogenic dyslipidemia recognized by the PROCAM coronary risk score

Assessing risk of myocardial infarction and stroke: new data from the Prospective Cardiovascular M√ľnster (PROCAM) study. Eur J Clin Invest 2007;37:925-32.

Assmann G, Schulte H, Cullen P, Seedorf U.
Summary
Comments & References
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STUDY SUMMARY
Objective To refine the scoring scheme for risk of myocardial infarction (MI) and to develop a scoring scheme for risk of ischemic stroke in the general population, based on the PROCAM data.
CORONARY RISK SCORE
Population 18,460 men and 8,515 women from the PROCAM study, without prior history of MI, angina or stroke. Subjects were recruited before 1996.
Follow-up duration Mean: 12 ± 6 years.
Methods The coronary risk score was derived using the Weibull proportional hazards model, with age as the time variable. The coronary risk score was based on an outcome analysis of 511 incident major coronary events (462 in men and 49 in women).
Results
  • Established cardiovascular risk factors included in the score were LDL cholesterol, HDL cholesterol, systolic blood pressure, smoking, triglycerides, diabetes, and family history of cardiovascular disease.
  • The risk score had high predictive accuracy in men and women over a 20-75 years age range (as shown by the Receiver Operating Characteristic (ROC) value reaching 0.82).
STROKE RISK SCORE
Population 5,905 men and 2,225 women, aged 35-65 years, from the PROCAM population
Follow-up duration ≥10 years
Methods The cerebral ischemic risk score was derived using the Cox proportional hazards model. The stroke risk score was based on an outcome analysis of 85 incident cerebral ischemic events (21 transient ischemic attacks and 64 ischemic strokes).
Results
  • The score included five risk factors: age, sex, diabetes, smoking and systolic blood pressure.
  • The score had a high predictive accuracy (ROC = 0.78).
Author's Conclusion These PROCAM risk scores provide simple and effective ways to assess the risk of acute coronary events and ischemic stroke in the general population, and will help physicians to apply appropriate primary prevention measures in high-risk subjects.

COMMENT

Current recommendations for the prevention of cardiovascular disease stress the need to base interventions on assessment of global risk, rather than considering each risk factors in isolation. This is because most people who develop atherosclerotic vascular disease will often have several risk factors which interact to synergistically increase the overall ensuing cardiovascular risk. The increasing prevalence of metabolic syndrome, a clustering of risk factors including impaired glucose homeostasis, hypertension, raised triglycerides, low levels of high-density lipoprotein (HDL) cholesterol, typically associated with central obesity, underlines the relevance of global risk assessment to current clinical practice. Individuals with metabolic syndrome are nearly twice as likely to die from cardiovascular disease, and their risk of myocardial infarction and stroke is about 3-fold higher compared with those without the condition.1,2

Considerable effort has been made to develop and refine risk scores for estimating global cardiovascular risk. The Prospective Cardiovascular Münster (PROCAM) study was set up in 1978 to investigate the epidemiology of coronary heart disease (CHD). Analysis of outcome data from 10 years follow-up led to the development of the PROCAM risk score for coronary events. This risk score included LDL cholesterol, HDL cholesterol, systolic blood pressure, smoking, triglycerides, diabetes, and family history of cardiovascular disease. Of high relevance is the recognition that most of these characteristics happen to also represent components of the metabolic syndrome. Low levels of HDL cholesterol and elevated triglycerides – the primary components of atherogenic dyslipidemia, a frequent occurrence in patients with diabetes and/or metabolic syndrome – were identified as independent variables influencing coronary risk.3

Because the previous PROCAM risk score was derived from middle-aged men, its applicability to women and elderly (>65 years) men and women was limited. Therefore, the initial aim of this report by the PROCAM Investigators was to develop an updated risk score which could be extended to both men and women across a wider age range. The Weibull proportional hazards model was used, in which age was the time variable (rather than time as in the Cox regression model); this provided with a much improved means of modeling the data. This updated PROCAM risk score showed good agreement between estimated and observed event rates in both men and women, as demonstrated by ROC statistics, a means of assessing the performance of such as predictive score.

Addressing the need for a simple tool to assess stroke risk
Coronary and cerebral ischemic events share a number of common risk factors, since both conditions are mainly due to atherosclerosis and/or hypertension. However, while there has been much effort in the development of risk scores for estimating coronary risk, the need for a simple risk assessment tool for stroke that is widely applicable has not been properly addressed except for type 2 diabetic patients (UKPDS Risk Score). This is especially relevant given that stroke is an important public health problem, with paramount clinical, economic and quality of life implications. The most widely used risk score for non-diabetic subjects in primary prevention is the Framingham stroke score, although this was based on data at least 30 years old (4). The Framingham cohort was also predominantly white, middle-aged suburban Americans with a low prevalence of classical cardiovascular risk factors, which may preclude wider generalization of the risk function to other populations.

In the current report, only five variables – age, sex, smoking, diabetes and systolic blood pressure – were included in the PROCAM cerebral ischemic risk score. This is consistent with data from the Atherosclerosis Risk in Communities study, which showed that the presence of elevated blood pressure and/or elevated fasting glucose were key components of the metabolic syndrome associated with increased risk of stroke.2 The PROCAM Investigators highlighted evidence of a disproportionately high event rate in individuals at high risk of stroke (³10-year event rate). In this group, which comprised only 4% of PROCAM subjects, there were 31% of all strokes (82 events) (Figure 1). These data underline the relevance of targeting intervention to those individuals who need it most.

In conclusion, this report describes two simple risk scores that can be used by clinicians to assess global cardiovascular risk. The PROCAM coronary risk score highlights the need to address atherogenic dyslipidemia (low HDL cholesterol and elevated triglycerides) as components contributing to elevated risk. Additionally, the PROCAM cerebral ischemic risk score addresses an unmet need for a simple, generally applicable risk score that allows clinicians to target appropriate multifactorial intervention to reduce stroke risk.

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Figure 1: Cerebral ischemic event rates according to estimated 10-year risk using the PROCAM score.

References
  1. Ford ES. Risks for all-cause mortality, cardiovascular disease and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 2005;28:1769-78.
  2. Rodriguez-Colon SM, Mo J, Duan Y et al. Metabolic syndrome clusters and the risk of incident stroke. Stroke 2009;40:2000-5.
  3. Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the Prospective Cardiovascular Munster (PROCAM) study. Circulation 2002;105:310-5.
  4. Wolf PA, d’Agostino RB, Belanger AJ, Kannel W. Probability of stroke: a risk profile from the Framingham Study. Stroke 1991;22:312-8.
Key words Risk score – PROCAM – Coronary heart disease - Stroke