REVIEWIntensive Lowering of Low-Density Lipoprotein Cholesterol Levels for Primary Prevention of Coronary Artery Disease
Section snippets
ADVANCING AGE AND SEVERE AND MULTIPLE RISK FACTORS
In older individuals, the LDL-C goal is lower because this population has a much greater burden of coronary atherosclerosis than younger individuals and therefore increased CAD morbidity and mortality. The prevalence of clinical CAD is almost 3-fold higher for individuals older than 60 years compared with younger individuals, and CAD is the leading cause of death among older individuals.1
Many healthy older individuals without clinical CAD have subclinical atherosclerotic disease and are at
FAMILY HISTORY OF PREMATURE CAD
The updated NCEP ATP III guidelines identified a strongly positive family history of premature atherosclerotic cardiovascular disease as a severe risk factor that, when present in moderately high-risk individuals, would favor the use of a lipid-lowering drug to achieve an LDL-C goal of less than 100 mg/dL. An individual with a first-degree male relative who had a CAD event before the age of 55 years or a first-degree female relative who had a CAD event before the age of 65 years is considered
METABOLIC SYNDROME, HIGH TRIGLYCERIDE LEVELS, AND LOW HDL-C LEVELS
The metabolic syndrome represents a constellation of lipid and nonlipid risk factors that together increase the risk of CAD independently of LDL-C levels.22, 23 The NCEP ATP III defines the metabolic syndrome as a diagnosis of 3 or more of the following risk factors: waist circumference greater than 40 inches for men or greater than 35 inches for women, triglyceride levels of 150 mg/dL or higher (to convert to mmol/L, multiply by 0.0113), HDL-C levels of less than 40 mg/dL for men or less than
EMERGING RISK FACTORS
The updated NCEP ATP III guidelines identified 2 emerging risk factors that would favor an LDL-C goal of less than 100 mg/dL for the primary prevention of CAD in moderately high-risk individuals: elevated serum high-sensitivity CRP level greater than 3 mg/L (to convert to nmol/L, multiply by 9.524) and a coronary calcium level in the higher than 75th percentile for a person's age and sex.
Inflammation plays a key role in both the development and progression of atherosclerotic CAD. The most
DISCUSSION
The current evidence supports a strategy of early and aggressive lowering of LDL-C levels for the primary prevention of CAD. Cohen et al43 studied a group of individuals with nonsense mutations in the PCSK9 gene that caused low levels of LDL-C. Although their LDL-C level was only 28% lower than the population without the PCSK9 mutation, their CAD risk was 88% lower. The implications from that study are that a low level of LDL-C throughout life is associated with a very low risk of CAD. Lowering
CONCLUSION
Physicians need to treat moderate-risk patients with lipid-lowering therapy to achieve a lower LDL-C goal of less than 100 mg/dL if the patients have multiple risk factors, an elevated CRP level, or other clinical risk factors identified in the updated NCEP ATP III guidelines. With increased adherence to these guidelines, opportunity exists to substantially reduce the incidence of a first cardiovascular event in higher-risk patients.
Acknowledgments
Editorial support was provided by Chris Cadman of Envision Pharma, a medical writer funded by Pfizer.
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Statin treatment decreases serum angiostatin levels in patients with ischemic heart disease
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Dr Karalis has received research and grant support from Pfizer and Abbott Pharmaceuticals and is on the speaker's bureau for Pfizer, Abbott, Sanofi-Aventis, and Merck-Schering-Plough Pharmaceuticals.