The relevance of apolipoprotein levels, particularly apoB, to cardiovascular risk is increasingly appreciated.21 ApoB concentration represents the sum of atherogenic particles found on all atherogenic lipoproteins, including very-low-density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein, and lipoprotein(a) cholesterol, whereas apoA represents the sum of antiatherogenic particles found on high-density lipoprotein cholesterol (HDL-C), the antiatherogenic lipoprotein.22 The ratio of apoB/apoA-I has, in fact, been shown to be a good predictor of cardiovascular events in young men without hypertension and diabetes but with chest pain.23 High-sensitivity C-reactive protein is a sensitive marker of acute inflammation and is associated with coronary risk.24 Measuring hs-CRP is a recommended option to determine enhanced absolute risk in people with an intermediate 10-year CHD risk of 10% to 20%.25
There remains some uncertainty regarding which lipid levels should be measured when screening for cardiovascular risk. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) advises that total cholesterol, LDL-C, HDL-C, and triglycerides be measured.26 More recent results from The Emerging Risk Factors Collaboration suggest that a more simplified approach may be reasonable.27 Review of data from 68 long-term prospective studies involving 302,430 people without initial vascular disease and 2.79 million person-years of follow-up showed that lipid assessment of vascular risk could be accomplished by measuring either total cholesterol and HDL-C levels or apolipoprotein levels; measuring the triglyceride level was of no added benefit in assessing vascular risk. In addition, fasting and nonfasting lipid levels were found to be of similar value in assessing risk. Other evidence shows that the combination of a triglyceride level ≥178 mg/dL and waist circumference ≥35.4 inches—the hypertriglyceridemic waist phenotype—is as discriminatory a screening tool as the NCEP ATP III guidelines to identify individuals at increased cardiometabolic risk.28 The use of more comprehensive lipoprotein and apolipoprotein testing, as well as noninvasive imaging, may have value in future cardiovascular risk assessment.
Treatment
The main goal of treatment in persons with 1 or more modifiable risk factors is to prevent an incident or primary cardiovascular event. Treatment strategies to achieve this goal in men and women are the same. Prevention of recurrent or secondary events will not be addressed here.
Lipids
Numerous clinical trials, such as the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS),29 Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA),30 and West of Scotland Coronary Prevention Study (WOSCOPS),31 definitively established the benefit of cardiovascular risk reduction with lipid-lowering treatment, particularly LDL-C-lowering treatment. Low-density lipoprotein cholesterol is the principal lipid target in most patients, with the treatment goal based on the presence of additional risk factors.32 Discussion of treatments for low HDL-C and elevated triglyceride levels is beyond the scope of this review but is expected to be included in the NCEP ATP IV guidelines scheduled for release later in 2012.
The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) also established significant benefits of statin therapy in primary prevention, compared with placebo, in persons with normal or modestly elevated LDL-C (<130 mg/dL) and elevated hs-CRP (≥2 mg/L).33 Rates of the primary end point (MI, stroke, arterial revascularization, hospitalization for unstable angina, or cardiovascular death) were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio [HR], 0.56; 95% CI, 0.46-0.69; P < .00001). Further analysis showed that patients who achieved LDL-C <70 mg/dL had a 55% lower rate of vascular events compared with placebo.34
Results from large primary prevention clinical trials such as JUPITER have led to recommendations over the past decade or so for progressively lower LDL-C goals. A meta-analysis of 25 large clinical trials involving 155,613 subjects showed that for every 25 mg/dL reduction in LDL-C, the RR for several cardiovascular outcomes was reduced: vascular mortality, 0.89; major vascular events, 0.86; major coronary events, 0.84; and stroke, 0.90. Put differently, there was a 20% reduction in major coronary events for every 39 mg/dL LDL-C reduction.35
Recent trials support the benefits of intensive high-dose statin therapy in greatly reducing lipid levels, with associated benefits in terms of cardiovascular events. A meta-analysis of 7 trials involving 50,972 high-risk patients with a mean follow-up of 3.1 years showed significant reductions in the risk for cardiovascular events with intensive statin therapy. Those who achieved LDL-C <82 mg/dL with intensive statin therapy had lower cardiovascular risks compared with those with LDL-C ≥82 mg/dL: stroke, odds ratio (OR): 0.80; major coronary events, OR: 0.74; and CVD or CHD death, OR: 0.84.36 Significantly higher liver enzyme abnormalities were observed in patients treated with high-dose statin therapy. [See also Addressing Key Questions with Statin Therapy in this supplement.] The benefits of intensive statin therapy on the progression of coronary atherosclerosis have also been investigated. The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin versus Atorvastatin (SATURN) by Nicholls et al37 included patients (N = 1039) with documented coronary vessel stenosis of at least 20% and a target vessel for imaging with less than 50% obstruction. Patients received either atorvastatin 80 mg daily or rosu-vastatin 40 mg daily for 104 weeks. In the rosuvastatin group, end-of-study LDL-C levels were lower (62.6 vs 70.2 mg/dL; P < .001) and HDL-C levels higher (50.4 vs 48.6 mg/dL; P = .01) compared with the atorvastatin group, respectively. The percent atheroma volume decreased by 1.22% with rosuvastatin and 0.99% with atorvastatin (P = .17). The normalized total atheroma volume decreased 6.39 mm3 with rosuvastatin and 4.42 mm3 with atorvastatin (P = .01). Atheroma regression was induced in the majority of patients in both groups.