Preventing cardiovascular disease in the 21st century: therapeutic and preventive implications of current evidence.

Cardiovascular disease (CVD), particularly coronary heart disease (CHD), remains a major cause of mortality, morbidity, and disability in the US and other Westernized societies. As a result of therapeutic and preventive measures to control the CVD/CHD epidemic, mortality has declined steadily during the last several decades with a consequent gain in life expectancy, but the 1990s witnessed a slowing of this decline. In response to these trends, a range of therapeutic regimens were developed to address adverse CVD risk factor levels and their deleterious effects. The scientific evidence regarding the efficacy, cost effectiveness, strengths, and limitations of a range of pharmacologic and lifestyle approaches to CVD prevention--both primary and secondary--are reviewed in depth. Clinical trials aimed at primary and secondary prevention of CVD have documented the efficacy and cost effectiveness of various drugs in lowering individual risk factor levels and in reducing clinical CVD events. More recently, the idea of a 'polypill' containing low doses of multiple drugs has generated much interest, with proponents arguing that, given the high prevalence of CVD risk factors and the effectiveness of pharmacologic interventions, such a drug combination would reduce CHD mortality by 88% if taken by all individuals aged > or = 55 years. However, current treatments to control high BP and serum cholesterol, while effective, do not typically reduce morbidity and mortality to levels observed in low-risk individuals, i.e. those with favorable levels of all readily measured major risk factors. Rather, primary prevention of all major risk factors starting early in life is critical. Prospective population-based research has delineated multiple long-term benefits associated with low-risk status in young adulthood and middle age, i.e. markedly lower age-specific CVD and total mortality rates, increased life expectancy, lower healthcare costs, lower medication use and prevalence of chronic diseases, and higher self-reported quality of life at older ages. Unfortunately, despite declines in the prevalence of most major CVD risk factors, low-risk status remains rare among US adults. Data have also demonstrated that adverse levels of one or more major risk factors precede clinical CHD in 90% or more of all cases, undermining the assertion that major CVD risk factors account for 'no more than 50%' of CHD cases. Hence, while numerous treatment options exist for secondary prevention of CVD, strategies that focus on progressively increasing the proportion of low-risk individuals could greatly reduce the need for secondary prevention in the first place. Public health policies must focus on prevention of all major risk factors simultaneously, using lifestyle approaches from early ages onwards to reduce population CVD risk to endemic levels, rather than current epidemic levels.