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The investigators used NHANES data for 2005 to 2010 to extrapolate the effects of the new 2013 cholesterol treatment guidelines across the United States. They estimate that the new guidelines would increase the number of adults eligible for statin therapy by 12.8 million. Until recently, the guidelines of the Third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program were the recommended guidelines to aid in the treatment of hyperlipidemia in the United States. 1 , 2 The ATP-III guidelines identified patients with established cardiovascular disease or diabetes and low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter (2.59 mmol per liter) or higher as candidates for statin therapy. In addition, the ATP-III guidelines recommended the use of statin therapy for primary prevention in patients on the basis of a combined assessment of LDL cholesterol level and the 10-year risk of coronary . . .

Apolipoprotein B (apo B) measurement is recommended as an alternative to low-density lipoprotein cholesterol (LDL-C) for assessing cardiovascular risk. The 2021 Canadian Cardiovascular Society guideline on dyslipidemia suggests using levels of non-high-density lipoprotein cholesterol (non-HDL-C) or apo B instead of LDL-C for screening and treatment targets. Apo B represents the total number of atherogenic particles, which is more closely associated with atherosclerosis than cholesterol concentration. Clinical trials have shown that apo B levels more accurately predict the risk of coronary heart disease compared to LDL-C or non-HDL-C levels. The guideline recommends statin treatment for patients with an intermediate Framingham Risk Score and an apo B level above a certain threshold. Apo B measurement has practical advantages over other measures, as it is inexpensive, reimbursed, and can be performed by all laboratories. It does not require fasting and remains accurate even with elevated triglycerides or low LDL-C levels. In some patients, LDL-C levels may appear satisfactory, but elevated apo B levels indicate a higher risk of cardiovascular disease. Treatment with lipid-lowering drugs should be considered in such cases.

It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant. Among 27533 initially healthy women in the Women's Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models. Although all 3 biomarkers were correlated ( ≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both < 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to nonHDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical risk factors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk. Discordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement of lipoprotein particle concentration might better inform CHD risk assessment.

Clinical decisions are increasingly driven by evidence-based recommendations of guideline groups, which aim to be based on the highest quality knowledge—randomized clinical trials (RCTs) and meta-analyses. Although RCTs provide the best assessment of the overall value of a therapy, high-quality evidence from RCTs is often incomplete, contradictory, or absent even in areas that have been most exhaustively studied. Moreover, the likelihood of the success or failure of a therapy is not identical in all the individuals treated in any trial because therapy is not the only determinant of outcome. Therefore, the overall results of a trial cannot be assumed to apply to any particular individual, not even someone who corresponds to all the entry criteria for the trial. In addition, the potential for bias due to financial conflicts remains in many guideline groups. Guidelines are key sources of knowledge. Nevertheless, limitations in the extent, quality, generalizability, and transferability of evidence mean that we clinicians must still reason through the best choices for an individual because even in the absence of full and secure knowledge, clinical decisions must still be made. Clinical reasoning is the pragmatic, tried-and-true process of expert clinical problem solving that does value mechanistic reasoning and clinical experience as well as RCTs and observational studies. Clinicians must continue to value clinical reasoning if our aim is the best clinical care for all the individuals we treat.

Objectives Whether “prediabetes” merits particular clinical attention beyond the management of associated risk factors is controversial, particularly given the expansion of the definition of prediabetes from HbA1c 6.0–6.4% to 5.7–6.4%. Accordingly, we compared the risk of atherosclerotic cardiovascular disease (ASCVD) and type II diabetes mellitus (DM) risk in male and female participants with prediabetes and HbA1c 5.7–6.0% (low) versus 6.1–6.4% (high) to examine whether preventive recommendations should prioritize treating blood sugar or obesity, the major determinants of risk of DM versus other causes of ASCVD, such as lipids and blood pressure. Research design and methods 10-year risks of ASCVD and DM risk were determined separately in 296,470 women and men, age 40–73, from UK Biobank, free of ASCVD and DM at baseline. Cox proportional hazards regression with adjustment for conventional risk factors and Kaplan–Meier estimators were used with low (HbA1c 5.7–6.0%) and high prediabetes (HbA1c 6.1–6.4%) as primary exposuress with further stratification and adjustment for waist circumference. Results In multivariate-adjusted models, low and high prediabetes was associated with increased risk of ASCVD versus normal HbA1c in both women (HR = 1.08, 95% CI 1.01,1.15 in low prediabetes and 1.25, 95% CI 1.14,1.38 in high prediabetes) and men (HR = 1.18, 95%CI 1.11,1.24 in low prediabetes and 1.27, 95% CI 1.17,1.38 in high prediabetes). The associations with new onset DM were substantially more potent, achieving HR of 4.05, 95%CI 3.73,4.40 in low prediabetic women versus 14.22, 95% CI 13.06,15.49 in high pre-diabetic women and 4.45, 95% CI 4.12,4.80 in low prediabetic men versus 15.59, 95% CI 14.43,16.85 in high pre-diabetic men. Furthermore, increasing waist circumference in low prediabetic men and all prediabetic women was associated with meaningful increase in DM risk. Conclusions The risks of progression to both new onset DM and ASCVD are significantly greater in the prediabetic population. This underscores the importance of preventing the development of DM and efforts to reduce cardiometabolic risk through optimizing multiple risk factors in both categories of prediabetes. Risk modification by waist circumference suggests weight and glucose lowering therapies should be targeted at those with highest risks.

OBJECTIVE:--The objective of this study was to examine the associations between the severity of hepatic steatosis and dyslipidemia in type 2 diabetes, including circulating apolipoprotein B100 (apoB) concentrations and lipoprotein particle size and numbers. RESEARCH DESIGN AND METHODS--Computed tomography imaging was used to assess hepatic fat content and adipose tissue distribution in 67 men and women with type 2 diabetes, withdrawn from antidiabetic medications preceding the study. Fasting serum lipoprotein number and size was determined by nuclear magnetic resonance. Insulin sensitivity was measured with a glucose clamp and a [6,6-²H₂]glucose isotope infusion. RESULTS:--Two-thirds of the cohort had fatty liver. Hepatic steatosis correlated with serum triglycerides (r = 0.40, P < 0.01) and lower HDL cholesterol (r = -0.31, P < 0.05). ApoB and LDL cholesterol did not, being virtually identical in those with or without steatosis. The association between serum triglycerides and hepatic steatosis was largely accounted for by greater triglyceride enrichment in VLDL particles, which were larger. Severe steatosis was also associated with 70% higher small, dense LDL concentrations. Visceral obesity did not fully explain these associations, and hepatic steatosis was better correlated with triglycerides than with hyperglycemia or hepatic insulin resistance (P > 0.05). CONCLUSIONS:--The presence of hepatic steatosis in type 2 diabetes does not appear to affect apoB levels, but potentially increases atherogenesis by increasing triglycerides, reducing HDL levels, and increasing small, dense LDL.