Faculty Bibliography

High-density lipoprotein (HDL) cholesterol level is a strong predictor of morbidity and mortality in the general population. Conflicting data exist on the protective effects of high HDL cholesterol in patients with optimal low-density lipoprotein (LDL) cholesterol levels. To determine the association of high HDL cholesterol with mortality in patients with LDL cholesterol levels <70 mg/dl who undergo percutaneous coronary intervention, 3,616 consecutive patients with LDL cholesterol levels <70 mg/dl who underwent percutaneous coronary intervention from July 1, 1999, to June 1, 2007, were retrospectively analyzed and followed through July 1, 2007. All-cause mortality was identified using the National Death Index. The mortality rates was 34.7, 25.2, 23.7, and 18.8 per 1,000 person-years in patients with HDL cholesterol levels of <40, 40 to 49, 50 to 59, and > or =60 mg/dl, respectively (p for trend <0.001). After multivariate adjustment for demographic characteristics, cigarette smoking, biochemical variables, and co-morbid conditions, the hazard ratios for mortality in patients with HDL cholesterol levels of 40 to 49, 50 to 59, and > or =60 mg/dl, compared with their counterparts with HDL cholesterol levels <40 mg/dl, were 0.68 (95% confidence interval [CI] 0.50 to 0.93), 0.55 (95% CI 0.35 to 0.85), and 0.45 (95% CI 0.27 to 0.74), respectively. For each 1-SD increase in HDL cholesterol level (14 mg/dl), the multivariate-adjusted hazard ratio for all-cause mortality was 0.68 (95% CI 0.58 to 0.79). In conclusion, in patients with LDL cholesterol levels <70 mg/dl who underwent percutaneous coronary intervention, a strong inverse association was present between HDL cholesterol level and all-cause mortality.

BACKGROUND: Few data are available on the use of statins after publication of the National Cholesterol Education Program Third Adult Treatment Panel (ATP-III) guidelines in 2001. OBJECTIVE: To determine changes in statin use and its impact on low-density lipoprotein cholesterol (LDL-C) control among US adults from 1999 to 2004. METHODS: High LDL-C levels and statin use among 1911 participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2004 were determined and compared with 1770 and 2094 participants of NHANES 1999-2000 and NHANES 2001-2002, respectively. Statin use was obtained from review of participants' drug containers. High LDL-C levels and LDL-C control were defined, using risk-specific cut-points from the ATP-III guidelines. RESULTS: Statins were taken by 24 million Americans in 2003-2004, an increase from 12.5 million in 1999-2000. In 1999-2000, 2001-2002, and 2003-2004, statins were being used by 19.6%, 27.3%, and 35.9% of US adults with high LDL-C levels, respectively (p trend <0.001). Age-standardized mean LDL-C declined from 119.9 to 112.0 to 100.7 mg/dL among statin users between 1999-2000, 2001-2002, and 2003-2004. LDL-C control to ATP-III recommended targets was achieved by 49.7%, 67.4%, and 77.6% of statin users in 1999-2000, 2001-2002, and 2003-2004, respectively (p trend <0.001). Among US adults with high LDL-C, after multivariate adjustment, non-Hispanic blacks were 39% less likely (prevalence ratio = 0.61; 95 CI 0.39 to 0.97) than non-Hispanic whites to be taking statins. CONCLUSIONS: Statin use continues to increase among US adults and this has led to substantial improvements in LDL-C control. Nevertheless, suboptimal statin use, especially among racial/ethnic minorities, continues to prevent the maximal public health benefit from this effective drug class.

Previous studies indicated that serum cystatin C, a marker of renal function, was associated with cardiovascular disease (CVD). However, few data about this association are available for persons without chronic kidney disease or albuminuria. Data from 4,991 subjects in the Third National Health and Nutrition Examination Survey with an estimated glomerular filtration rate > or =60 ml/min/1.73 m2 without micro- or macroalbuminuria were analyzed. Subjects were categorized into quartiles of serum cystatin C and compared for prevalence of CVD. CVD was defined as a history of myocardial infarction, angina, or stroke. After age standardization, prevalences of CVD from the lowest to highest quartile of serum cystatin C were 6.0%, 8.8%, 11.8%, and 16.7% (p-trend = 0.006). Also, age-standardized prevalences of myocardial infarction across quartiles of serum cystatin C were 1.9%, 4.4%, 6.6%, and 8.6%; age-standardized prevalences of angina were 2.4%, 4.4%, 4.2%, and 7.1%; and age-standardized prevalences of stroke were 2.5%, 1.6%, 3.5%, and 4.4% (each p-trend <0.05). Each 1-SD higher serum cystatin C level was associated with a multivariate prevalence ratio of CVD of 1.55 (95% confidence interval [CI] 1.13 to 2.13), and multivariate-adjusted prevalence ratios were 1.44 (95% CI 1.01 to 2.07), 1.64 (95% CI 1.02 to 2.64), and 1.65 (95% CI 1.06 to 2.56) for myocardial infarction, angina, and stroke, respectively. In conclusion, a graded association exists between higher serum cystatin C and increased CVD prevalence in patients without established chronic kidney disease.

BACKGROUND: Although high body mass index (BMI) is a risk factor for hypertension, diabetes, and cardiovascular disease, limited data exist on the association of overweight and obesity with early stages of kidney disease. METHODS: Cross-sectional data for 5083 participants of the nationally representative Third National Health and Nutrition Examination Survey with an estimated glomerular filtration rate > or = 60 mL/min/1.73 m(2) without micro- or macroalbuminuria were analyzed to determine the association between BMI and elevated serum cystatin C. Normal weight, overweight, class I obesity, and class II to III obesity were defined as a BMI of 18.5 to 24.9 kg/m(2), 25.0 to 29.9 kg/m(2), 30.0 to 34.9 kg/m(2), and > or = 35.0 kg/m(2), respectively. Elevated serum cystatin C was defined as > or = 1.09 mg/L (> or = 99th percentile for participants 20-39 years of age without diabetes, hypertension, micro- or macroalbuminuria, or stage 3-5 chronic kidney disease). RESULTS: The age-standardized prevalence of elevated serum cystatin C was 9.6%, 12.9%, 17.4%, and 21.5% among adults of normal weight, overweight, class I obesity, and class II to III obesity, respectively (P trend < .001). After multivariate adjustment for demographics, behaviors, systolic blood pressure, and serum biomarkers, and compared with participants of normal weight, the odds ratio (95% confidence interval) of elevated serum cystatin C was 1.46 (1.02-2.10) for overweight, 2.36 (1.56-3.57) for class I obesity, and 2.82 (1.56-5.11) for class II to III obesity. CONCLUSION: A graded association exists between higher BMI and elevated serum cystatin C. Further research is warranted to assess whether reducing BMI favorably affects elevated serum cystatin C and the development of chronic kidney disease.

To determine whether statin use leads to dietary indiscretion, this longitudinal cohort study examined the impact of statin initiation on saturated fat intake. We interviewed 71 patients who had received a new prescription for statins for primary prevention of cardiovascular disease, first at the time of prescription and then again 3 and 6 months later. Patients were asked about their beliefs regarding diet and medications as well as their diet during the past 24 hours in all interviews and about their adherence to statins in the 3- and 6-month follow-up interviews. At the time of statin prescription, 54 participants (76 percent) wanted to reduce dietary fat, 50 (70 percent) believed statin use could cure their hyperlipidemia, and 31 (44 percent) thought that physicians prescribed statins to them despite their preference to continue to try dietary changes. After 6 months of statin use, no significant change in saturated fat intake was noted

PURPOSE: Statins are potent drugs for reducing cholesterol and cardiovascular disease; however, their effectiveness is significantly compromised by poor adherence. This prospective study was designed to identify potentially modifiable patient factors including medication, disease, and diet beliefs related to statin adherence. METHODS: Veterans (n = 71) given their first prescription of a statin for primary prevention were interviewed at baseline, 3 months, and 6 months regarding medication, disease, and diet beliefs along with self-reported statin adherence. RESULTS: At 6-month follow-up, 55% of the cohort was non-adherent with 10% reporting never having started their statin, 50% reporting misconceptions about the duration of treatment and a median use of <2 months among those who discontinued their statin. Multivariate predictors of non-adherence were expected short treatment duration (OR = 3.6, 1.4-9.4), low perceived risk of myocardial infarction (OR = 3.1, 1.1-8.7), concern about potential harm from statins (OR = 2.5, 1.0-6.3), being Hispanic (OR = 3.9, 1.0-15.2), and younger age (OR = 4.2, 1.1-15.8). CONCLUSIONS: Poor adherence to statins was common in this primary prevention population with frequent early discontinuation despite access to low-cost medicines. Patient factors regarding the perception of risk, toxic effects of medication, expected treatment duration, as well as socio-demographic factors, were significant predictors of poor adherence and warrant further exploration

BACKGROUND: While lipid-lowering drugs reduce cardiovascular risk, there is concern that their use may discourage dietary restriction of saturated fat (SF). The purpose of this analysis was to evaluate the association between taking lipid-lowering drugs and SF intake. MATERIALS AND METHODS: We analyzed cross-sectional data on cholesterol and diet from 6,473 adult respondents in the National Health and Nutrition Examination Survey, 1999-2002. Respondents were classified into three groups: (1) no history of high cholesterol (Desirable Cholesterol or DC), (2) history of high cholesterol without current drug treatment (Non-Drug Treated or NDT), and (3) history of high cholesterol with active lipid-lowering medication use (Drug-Treated or DT). Regression models were used to compare the mean percentage of daily kilocalories from SF among the three groups while controlling for confounders. RESULTS: Unadjusted analyses revealed significantly lower mean daily intake of SF (% of Kcal/day) among DT respondents compared to both DC (-.40 SF; 95% Confidence Interval [CI], -0.71 to -0.08) and NDT respondents [-.36 SF; CI, -0.79 to 0.06]. The complete multivariate model controlling for all covariates (age, sex, education, race/ethnicity, current smoking, alcohol use, BMI, physical activity, cardiovascular disease, diabetes, hypertension) attenuated the relationship compared to D (-.35 SF, CI -0.7 to -0.01) and NDT (-.25 SF, CI -0.62 to 0.12) individuals. CONCLUSION: Taking lipid-lowering medications is associated with a lower intake of SF. However, a prospective study of diet and medication use is needed to definitively evaluate the relationship between lipid-lowering medications and SF intake

BACKGROUND.: It is unclear whether the coronary heart disease (CHD) mortality risk associated with obesity is mediated only through traditional CHD risk factors. This analysis evaluated the independent CHD mortality risk due to obesity and determined its population attributable risk (PAR). METHODS.: Using the NHANES I Epidemiologic Follow-up Study (1971-1992, n = 10,582), a diabetes-body mass index (BMI) variable was constructed. The hazard ratios (HR) for fatal CHD in the diabetes-BMI categories (adjusting for age, sex, race, exercise, education level, smoking, hypertension, cholesterol, and alcohol use) were determined and the PARs subsequently estimated. RESULTS.: Compared to lean non-diabetics, the HR (95% CI) for fatal CHD is 0.8 (0.7, 1.1) in overweight non-diabetics, 1.4 (1.3, 2.0) in obese non-diabetics, 2.2 (1.2, 4.0) in lean diabetics, 2.3 (1.4, 3.9) in overweight diabetics, and 3.3 (1.9, 8.9) in obese diabetics. The PAR% is -6.8 (-15.7, 1.8) in overweight non-diabetics, 6.1 (1.7, 11.1) in obese non-diabetics, 2.0 (0.3, 4.0) in lean diabetics, 2.2 (0.6, 4.3) in overweight diabetics, and 2.2 (0.8, 3.8) in obese diabetics. CONCLUSIONS.: Obesity is an independent risk factor for CHD mortality even after controlling for traditional CHD risk factors. The PAR for CHD death in obese non-diabetics is significant. Obesity should be aggressively treated in those without traditional CHD risk factors