Macrovascular Residual Risk Studies

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.

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