Relation between high-density lipoprotein cholesterol and survival to age 85 years in men (from the VA normative aging study)

No previous researchers have sought to determine whether high-density lipoprotein (HDL) cholesterol levels are associated with survival to 85 years of age in a prospective cohort of aging men. We selected 652 men (mean age 65 years) enrolled in the VA Normative Aging Study who had ≥ 1 HDL cholesterol level documented during the study and who were old enough on the date of HDL cholesterol measurement to reach 85 years of age by the end of follow-up (July 1, 2008). We categorized initial HDL cholesterol into < 40 mg/dl (reference group), 40 to 49 mg/dl, or ≥ 50 mg/dl. Information on co-morbidities, lifestyle factors, measured lipid parameters, and medications were collected during triennial visits. We used proportional hazards to determine hazard ratios (HRs) for mortality before age 85 years for each category of initial HDL cholesterol compared to the reference adjusting for co-morbidities, calculated low-density lipoprotein cholesterol, medications, smoking, body mass index, and alcohol consumption. Treating HDL cholesterol as a continuous predictor, we also determined the HR for each 10-mg/dl increment in HDL cholesterol. Fully adjusted HR (95% confidence interval) for survival to 85 years of age for participants with an initial HDL cholesterol level ≥ 50 mg/dl compared to the reference was 0.72 (0.53 to 0.98). Each 10-mg/dl increment in HDL cholesterol was associated with a 14% (HR 0.86, 0.78 to 0.96) decrease in risk of mortality before 85 years of age. In conclusion, after adjusting for other factors associated with longevity, higher HDL cholesterol levels were significantly associated with survival to 85 years of age.     

Relation between on-treatment increments in serum high-density lipoprotein cholesterol levels and cardiac mortality in patients with coronary heart disease (from the Bezafibrate Infarction Prevention trial)

This study evaluated the association between changes in serum levels of high-density lipoprotein (HDL) cholesterol that occur under bezafibrate therapy and cardiac mortality in patients with coronary heart disease (CHD) who were enrolled in the Bezafibrate Infarction Prevention trial. We compared serum levels of HDL cholesterol in 1,509 patients in tertiles of on-treatment increments with those of 1,517 patients in the placebo group. Long-term follow-up showed that cardiac mortality decreased significantly with increasing tertiles of on-treatment change in HDL cholesterol (9.5%, 6.6%, and 6.3% of patients tertiles 1, 2, and 3, respectively, died of cardiac causes, p for trend = 0.02). In multivariate analysis, the magnitude of on-treatment increment of HDL cholesterol was independently associated with a decreased risk of cardiac death (hazard ratio 1.05, 95% confidence interval 0.74 to 1.47, for tertile 1; hazard ratio 0.73, 95% confidence interval 0.50 to 1.07, for tertile 2; hazard ratio 0.65, 95% confidence interval 0.43 to 0.97, for tertile 3, compared with placebo-allocated patients, p for trend = 0.02). Analyzing the association with change in HDL cholesterol as a continuous variable showed that the risk of cardiac mortality was decreased by 27% for every 5-mg/dl increase in on-treatment change in HDL cholesterol (p <0.001). In conclusion, although a definite secondary prevention effect of bezafibrate could not be found when examining the intervention group as a whole, our findings are consistent with a possible independent association between an increase in HDL cholesterol with bezafibrate therapy and a decrease in cardiac mortality. In appropriately selected patients, monitoring short-term response to bezafibrate therapy through change in HDL cholesterol may indicate the potential long-term benefit of the drug.     

Effects of high-dose atorvastatin on cerebrovascular events in patients with stable coronary disease in the TNT (treating to new targets) study.

OBJECTIVE: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl. BACKGROUND: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated. METHODS: We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years. RESULTS: Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95% confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95% CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95% CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6% relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5% relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment. CONCLUSIONS: Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).     

A population-based, cross-sectional comparison of lipid-related indexes for symptoms of atherosclerotic disease

Current lipid guidelines recommend that therapy be targeted primarily at low-density lipoprotein (LDL) cholesterol, and that other lipid indexes may be used as secondary or supplementary targets. Emerging data have suggested that measures such as non-high-density lipoprotein (HDL) cholesterol, apolipoprotein-B, or the total/HDL cholesterol ratio may be more predictive of cardiovascular risk than LDL cholesterol. We conducted a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey to directly compare the strengths of the associations among various lipid-related indexes and clinical features consistent with atherosclerotic disease. From approximately 9,500 data sets in the overall analysis, the apolipoprotein-B/HDL cholesterol ratio emerged as the strongest correlate (odds ratio 1.177 per 1 mg/dl increment, 95% confidence interval 1.063 to 1.302, p <0.01), followed by the total or non-HDL cholesterol/HDL cholesterol ratio (odds ratio for each 1.070 per 1 mg/dl increment, 95% confidence interval 1.024 to 1.118, p <0.01), followed by the triglyceride/HDL cholesterol ratio (odds ratio 1.033 per 1 mg/dl increment, 95% confidence interval 1.011 to 1.056, p <0.01). Neither LDL cholesterol nor the LDL/HDL cholesterol ratio correlated significantly. Parallel analyses comparing tertile extremes and analyses in subgroups determined by gender, age, and body mass index revealed similar findings. The LDL/HDL cholesterol ratio was only significant for lean patients. In conclusion, these observations add to the published data suggesting that LDL cholesterol may not be the best target of lipid-lowering treatment strategies.     

Impact of low high-density lipoproteins on in-hospital events and one-year clinical outcomes in patients with non-ST-elevation myocardial infarction acute coronary syndrome treated with drug-eluting stent implantation

High-density lipoprotein (HDL) cholesterol has protective cardiovascular effects. We investigated the effect of baseline HDL cholesterol on the outcomes of patients who underwent drug-eluting stent implantation for acute coronary syndrome. Since March 2003, 1,032 consecutive patients were, according to their baseline HDL cholesterol level, included in a low HDL cholesterol group (n = 550, <40 mg/dl in men, <45 mg/dl in women, mean 32 +/- 7) or a high HDL cholesterol group (n = 482, >40 mg/dl in men, >45 mg/dl in women, mean 55 +/- 19). End points were death, Q-wave myocardial infarction, target lesion revascularization, and a composite of major adverse cardiac events at 30 days and 1 year. We assessed the relation between HDL cholesterol and end points. Patients with low HDL cholesterol more often had diabetes, a higher body mass index, higher triglyceride levels, and lower total cholesterol levels. Low-density lipoprotein cholesterol and statin treatment (98% in the 2 groups) were comparable. Incidences of mortality and major adverse cardiac events at 30 days were higher in the low than in the high HDL cholesterol group (p <0.001 and p = 0.002, respectively; chi-square analysis). At 1 year, more deaths occurred in the low HDL cholesterol group (p <0.001; chi-square analysis), as did major adverse cardiac events (p <0.001; chi-square analysis). Multivariate analysis showed low HDL cholesterol at baseline (hazard ratio 2.61, 95% confidence interval 1.33 to 5.12) to be a key predictor of major adverse cardiac events and death (hazard ratio 3.33, 95% confidence interval 1.15 to 10.0) at 1 year. In conclusion, regardless of baseline low-density lipoprotein cholesterol levels and statin therapy, additional strategies to increase HDL cholesterol should be evaluated in patients with acute coronary syndrome.     

Comparison of effectiveness of atorvastatin 10 mg versus 80 mg in reducing major cardiovascular events and repeat revascularization in patients with previous percutaneous coronary intervention (post hoc analysis of the Treating to New Targets [TNT] Study)

The Treating to New Targets (TNT) study demonstrated that intensive atorvastatin therapy to achieve low-density lipoprotein cholesterol concentrations well below recommended target levels provides an incremental clinical benefit in patients with stable coronary artery disease. This post hoc analysis of the TNT study was conducted to investigate whether this benefit extends to patients with previous percutaneous coronary intervention (PCI). A total of 10,001 patients with clinically evident coronary artery disease, including 5,407 patients with previous PCI, were randomized to atorvastatin 10 or 80 mg/day and followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event. Revascularization, a component of a secondary end point, was also examined. In patients with previous PCI, mean low-density lipoprotein cholesterol levels at study end were 79.5 mg/dl in the 80-mg arm and 100.8 mg/dl in the 10-mg arm. First major cardiovascular events occurred in 230 patients (8.6%) receiving high-dose atorvastatin and 289 patients (10.6%) receiving low-dose atorvastatin (hazard ratio 0.79, 95% confidence interval 0.67 to 0.94, p = 0.008). Repeat revascularization during follow-up (PCI or coronary artery bypass grafting) was performed in 466 patients (17.3%) in the 80-mg arm and 624 patients (22.9%) in the 10-mg arm (hazard ratio 0.73, 95% confidence interval 0.65 to 0.82, p <0.0001). In conclusion, intensive lipid lowering to a mean low-density lipoprotein cholesterol level of 79.5 mg/dl (2.1 mmol/L) with atorvastatin 80 mg/day in patients with previous PCI reduces major cardiovascular events by 21% and repeat revascularizations by 27% compared with a less intensive lipid-lowering regimen.     

Uric acid and mortality from all-causes and cardiovascular disease among adults with and without diagnosed diabetes: findings from the National Health and Nutrition Examination Survey III Linked Mortality Study

Using data from the National Health and Nutrition Examination Survey III Linked Mortality Study, uric acid concentration was significantly related to mortality from all-causes (978 diabetic participants: hazard ratio per mg/dl, 1.14; 95% confidence interval, 1.01-1.28; 12,824 nondiabetic participants: hazard ratio, 1.06; 95% confidence interval, 1.02-1.11) but not major CVD.     

Major Lipids and Future Risk of Pneumonia: 20-Year Observation of the Atherosclerosis Risk in Communities (ARIC) Study Cohort

BackgroundCirculating lipids have been implicated as important modulators of immune response, and altered lipid levels correlate with the severity of infection. However, long-term prognostic implications of lipid levels regarding future infection risk remain unclear. The current project aims to explore whether baseline lipid levels are associated with risk of future serious infection, measured by hospitalization for pneumonia.MethodsA retrospective analysis was performed in 13,478 participants selected from the Atherosclerosis Risk in Communities (ARIC) study, a large community-based longitudinal cohort in the United States with a median follow-up time of >20 years. First incident of hospitalization for pneumonia was identified through hospital discharge records. Cox proportional hazard models were used to assess the association of baseline major lipid levels (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides) with time to first pneumonia hospitalization.ResultsA total of 1969 (14.61%) participants had a pneumonia hospitalization during a median follow-up time of 21.5 years. The hazard ratio (HR) for pneumonia hospitalization was 0.90 (95% confidence interval, 0.87-0.92) for every 10-mg/dL increase in baseline HDL-C, and 1.02 (95% confidence interval, 1.02-1.03) for every 10-mg/dL increase in baseline triglycerides. HDL-C and triglycerides both remained significant predictors of pneumonia hospitalization after multivariable adjustment. Such associations were not seen with baseline LDL-C or total cholesterol levels.ConclusionLower baseline HDL-C and higher triglyceride levels were strongly associated with increased risk of long-term pneumonia hospitalization in a large longitudinal US cohort.     

Efficacy of cholesterol levels and ratios in predicting future coronary heart disease in a Chinese population

In this study, we assessed the efficacy of various lipid and lipoprotein measurements at baseline for predicting the risk for coronary heart disease (CHD) and determined the associated risk of CHD in subgroups stratified by different lipid and lipoprotein screening strategies to evaluate the adequacy of current total and low-density lipoprotein (LDL) cholesterol-based approaches in lipid management. We analyzed data from the Chin-Shan Community Cardiovascular Cohort study, a Chinese population-based prospective cohort study that began in 1990. During an 8-year follow-up period, 213 of 3,159 participants (6.7%) without CHD (aged > or =35 years) developed CHD. The total cholesterol/high-density lipoprotein (HDL) cholesterol ratio was the most powerful lipoprotein predictor of future CHD (hazard ratio 1.21 for a 1.0 increment in ratio; p <0.001). Subjects with "high-risk" LDL cholesterol levels (>160 mg/dl) and low total cholesterol/HDL cholesterol ratios (< or =5) had an incidence of CHD similar to those with low levels of both LDL cholesterol (< or =130 mg/dl) and total cholesterol/HDL cholesterol ratios (4.9% vs 4.6%). In contrast, subjects with "low-risk" LDL cholesterol levels (< or =130 mg/dl) and high total cholesterol/HDL cholesterol ratios (>5) had a 2.5-fold higher incidence of CHD than those with similar LDL cholesterol levels but low total cholesterol/HDL cholesterol ratios (p <0.001). Compared with using an LDL cholesterol level of 130 mg/dl as the cut-off point, using a total cholesterol/HDL cholesterol ratio of 5 was associated with superior specificity (73% vs 59%, p <0.001) and accuracy (72% vs 58%, p <0.001), and similar sensitivity (50% vs 53%). Our data indicate that current guidelines for lipid management may misclassify subjects with high levels of HDL and LDL cholesterol as well as those with low levels of HDL and LDL cholesterol. Using the ratio of total to HDL cholesterol as the initial screening tool can obviate this discrepancy.     

CRP Level and HDL Cholesterol Concentration Jointly Predict Mortality in a Korean Population

BackgroundC-reactive protein (CRP) and high-density lipoprotein (HDL) cholesterol are well-known cardiovascular predictors. However, the joint effect of these parameters on long-term mortality has not been established.MethodsWe studied a total of 92,500 subjects older than 20 years who underwent routine health examination at the three health care centers affiliated with Seoul National University. High-sensitivity CRP and the lipid profile were obtained at baseline. Subjects were followed for a median of 45.5 months. Mortality data were obtained from the National Statistics Office of Korea.ResultsThere were 649 deaths (0.7%) during the follow-up. The leading cause of death was cancer. The subjects who died were significantly older, had a male predominance, and had increased levels of inflammatory markers. A significant mortality difference was identified according to the CRP and HDL cholesterol levels. Considering both parameters jointly, subjects with a CRP ≥1.4 mg/L (highest quartile) and HDL cholesterol <45 mg/dL (lowest quartile) were at the highest risk for all-cause mortality, even after adjusting for covariates (hazard ratio 2.29, 95% confidence interval, 1.83～2.87). After matching on the propensity score, 6304 subjects with a high CRP and low HDL cholesterol were at high risk of death (hazard ratio 2.52, 95% confidence interval, 1.59～4.01). Interestingly, the joint effect of CRP and HDL cholesterol was observed for cardiovascular as well as cancer-related mortality prediction.ConclusionsElevated CRP and low HDL cholesterol jointly contribute to the prediction of all-cause, cancer, and cardiovascular mortality in Koreans. The interactive relationship between them in mediating inflammatory processes might explain these results.     

Role of non-high-density lipoprotein cholesterol in predicting cerebrovascular events in patients following myocardial infarction

Although there appears to be a role for statins in reducing cerebrovascular events, the exact role of different lipid fractions in the etiopathogenesis of cerebrovascular disease (CVD) is not well understood. A secondary analysis of data collected for the placebo arm (n = 2,078) of the Cholesterol and Recurrent Events (CARE) trial was performed. The CARE trial was a placebo-controlled trial aimed at testing the effect of pravastatin on patients after myocardial infarction. Patients with histories of CVD were excluded from the study. A Cox proportional-hazards model was used to evaluate the association between plausible risk factors (including lipid fractions) and risk for first incident CVD in patients after myocardial infarction. At the end of 5 years, 123 patients (6%) had incident CVD after myocardial infarction (76 with stroke and 47 with transient ischemic attack). Baseline non-high-density lipoprotein (HDL) cholesterol level emerged as the only significant lipid risk factor that predicted CVD; low-density lipoprotein cholesterol and HDL cholesterol were not significant. The adjusted hazard ratios (adjusted for age, gender, hypertension, diabetes mellitus, and smoking) for CVD were 1.28 (95% confidence interval [CI] 1.06 to 1.53) for non-HDL cholesterol, 1.14 (95% CI 0.96 to 1.37) for low-density lipoprotein cholesterol, and 0.90 (95% CI 0.75 to 1.09) for HDL cholesterol (per unit SD change of lipid fractions). This relation held true regardless of the level of triglycerides. After adjustment for age and gender, the hazard ratio for the highest natural quartile of non-HDL was 1.76 (95% CI 1.05 to 2.54), compared to 1.36 (95% CI 0.89 to 1.90) for low-density lipoprotein cholesterol. In conclusion, non-HDL cholesterol is the strongest predictor among the lipid risk factors of incident CVD in patients with established coronary heart disease.     

Risk factors for coronary artery disease in patients with elevated high-density lipoprotein cholesterol

High high-density lipoprotein (HDL) levels protect against coronary artery disease (CAD) development. We hypothesized that patients with CAD and high HDL levels would have higher prevalence of other CAD risk factors compared with patients with CAD and normal HDL. We identified 41,982 patients from a single center with normal levels (40 to 60 mg/dl in men, 50 to 70 mg/dl in women) or high HDL levels (> or =70 mg/dl in men, > or =80 mg/dl in women) when last measured between January 2000 and April 2004. From this overall population, we characterized a cohort of 1,610 patients with CAD, including 98 patients with high HDL levels. We measured prevalence of traditional CAD risk factors by comparing these 98 patients with patients with CAD and normal HDL levels (n = 1,512). We performed manual chart review in patients (n = 196) matched 1:1 by age, gender, and HDL level to obtain further detail with regard to differences in family history and lifestyle factors. In patients with CAD, those with high HDL levels (98 of 1,610, 6.1%) were of similar age (71.1 vs 69.6 years, p = 0.23), had similar prevalence of hypertension (78.6% vs 88.7%, p = 0.30), lower levels of low-density lipoprotein (85.3 vs 90.9 mg/dl, p = 0.04) and triglycerides (87.1 vs 141.2 mg/dl, p <0.01), and a lower prevalence of diabetes (28.6% vs 38.4%, p = 0.05) compared with patients with normal HDL levels. In logistic regression models, patients with high HDL levels and CAD were less likely to have diabetes (adjusted odds ratio 0.60, 95% confidence interval 0.38 to 0.95, p = 0.03) or obesity (adjusted odds ratio 0.50, 95% confidence interval 0.25 to 0.99, p = 0.046) than patients with normal HDL levels and CAD. In conclusion, patients with high HDL and CAD had a similar or lower prevalence of traditional CAD risk factors compared with patients with normal HDL levels and CAD.     

Cystatin-C and mortality in elderly persons with heart failure

OBJECTIVES: We sought to evaluate cystatin-C, a novel measure of renal function, as a predictor of mortality in elderly persons with heart failure (HF) and to compare it with creatinine. BACKGROUND: Renal function is an important prognostic factor in patients with HF, but creatinine levels, which partly reflect muscle mass, may be insensitive for detecting renal insufficiency. METHODS: A total of 279 Cardiovascular Health Study participants with prevalent HF and measures of serum cystatin-C and creatinine were followed for mortality outcomes over a median of 6.5 years. RESULTS: Median creatinine and cystatin-C levels were 1.05 mg/dl and 1.26 mg/l. Each standard deviation increase in cystatin-C (0.35 mg/l) was associated with a 31% greater adjusted mortality risk (95% confidence interval [CI] 20% to 43%, p < 0.001), whereas each standard deviation increase in creatinine (0.39 mg/dl) was associated with a 17% greater adjusted mortality risk (95% CI 1% to 36%, p = 0.04). When both measures were combined in a single adjusted model, cystatin-C remained associated with elevated mortality risk (hazard ratio 1.60, 95% CI 1.32 to 1.94), whereas creatinine levels appeared associated with lower risk (hazard ratio 0.73, 95% CI 0.57 to 0.95). CONCLUSIONS: Cystatin-C is a stronger predictor of mortality than creatinine in elderly persons with HF. If confirmed in future studies, this new marker of renal function could improve risk stratification in patients with HF.     

Accuracy of the triglyceride to high-density lipoprotein cholesterol ratio for prediction of the low-density lipoprotein phenotype B

This study examined the accuracy of a triglyceride/high-density lipoprotein (HDL) cholesterol ratio of 3.8 for the prediction of low-density lipoprotein (LDL) phenotype B. The ratio of 3.8 was based on Adult Treatment Panel recommendations for normal fasting triglycerides (<150 mg/dl) and HDL cholesterol (>40 mg/dl). Fasting blood samples were obtained from 658 patients. LDL phenotype analysis was performed by nuclear magnetic resonance spectroscopy. A triglyceride/HDL cholesterol ratio of 3.8 divided the distribution of LDL phenotypes with 79% (95% confidence interval [CI] 74 to 83) of phenotype B greater than and 81% (95% CI 77 to 85) of phenotype A less than the ratio of 3.8. The ratio was reliable for identifying LDL phenotype B in men and women.     

Relation between obesity and the attainment of optimal blood pressure and lipid targets in high vascular risk outpatients

Obesity is associated with hypertension, dyslipidemia, and diabetes, but it is also an independent cardiovascular risk factor. We sought to evaluate the differences in treatment patterns and attainment of guideline-recommended targets among high-risk vascular outpatients in relation to their body mass index (BMI). The prospective Vascular Protection and Guideline Orientated Approach to Lipid Lowering Registries recruited 7,357 high-risk vascular outpatients in Canada from 2001 to 2004. We stratified the patient population into 3 groups according to their BMI: normal weight (BMI <24.9 kg/m2), overweight (BMI 25 to 29.9 kg/m2), and obese (BMI >30 kg/m2). We evaluated the rates of attainment for contemporary guideline targets of blood pressure (<140/90 or <130/80 mm Hg in the presence of diabetes) and lipids (low-density lipoprotein [LDL] <2.5 mmol/L [96.7 mg/dl] and total cholesterol [TC]/high-density lipoprotein [HDL] ratio <4.0). Of the 7,357 patients, 1,305 (17.7%) were normal weight, 2,791 (37.9%) overweight, and 3,261 (44.4%) obese, as determined by the BMI. Obese patients were younger and more likely to have hypertension and diabetes (all p <0.001 for trend). Obese patients had higher baseline blood pressure, TC, LDL cholesterol, triglyceride levels and TC/HDL ratio, and lower HDL cholesterol. Obese patients were more likely to be treated with antihypertensive agents (p = 0.002), angiotensin-converting enzyme inhibitors (p = 0.024), angiotensin receptor blockers (p <0.001), and high-dose statin therapy (p = 0.001). On multivariable analyses, obese patients were less likely to attain the blood pressure (odds ratio 0.77, 95% confidence interval 0.66 to 0.90, p = 0.001) and TC/HDL ratio (odds ratio 0.48, 95% confidence interval 0.42 to 0.55, p <0.001) targets but not the LDL targets (odds ratio 0.89, 95% confidence interval 0.78 to 1.03, p = 0.11). In conclusion, only a minority ambulatory patients at high cardiovascular risk achieved both guideline-recommended blood pressure and lipid targets, and this significant treatment gap was more pronounced among obese patients. Our findings underscore the opportunity to optimize the treatment of these high-risk patients.     

Relation of improvement in estimated glomerular filtration rate with atorvastatin to reductions in hospitalizations for heart failure (from the Treating to New Targets [TNT] study)

Impaired kidney function often accompanies heart failure (HF) and is associated with a worse prognosis. This post hoc analysis of the Treating to New Targets (TNT) trial examined whether the observed decrease in HF hospitalizations with high- compared to low-dose atorvastatin could be related to improvements in kidney function. Of 10,001 TNT participants, 9,376 had estimated glomerular filtration rate (eGFR) measurements at baseline and 1 year and were included in this analysis. The association of change in year-1 eGFR and subsequent HF hospitalization was examined using Cox regression models. In total 218 participants developed subsequent HF hospitalization. Little change in eGFR occurred over 1 year in the atorvastatin 10-mg group, whereas eGFR improved in the 80-mg group by 1.48 ml/min/1.73 m(2) (95% confidence interval 1.29 to 1.67, p <0.0001). Subsequent HF was preceded by a decrease in eGFR over 1 year compared to modest improvement in those without subsequent HF (-0.09 ± 7.89 vs 0.81 ± 6.90 ml/min/1.73 m(2), p = 0.0015). After adjusting for baseline eGFR, each 5-ml/min/1.73 m(2) increase in eGFR at 1 year was associated with a lower risk of subsequent HF hospitalization (hazard ratio 0.85, 95% confidence interval 0.77 to 0.94, p = 0.002). This relation was independent of treatment effect or change in low-density lipoprotein cholesterol level at 1 year. In conclusion, treatment with high- compared to low-dose atorvastatin was associated with improvement in eGFR at 1 year, which was related to a decrease in subsequent HF hospitalization. This suggests that improvement in kidney function may be related to the beneficial effect of high-dose atorvastatin on HF hospitalization.     

Effect of the metabolic syndrome and hyperuricemia on outcome in patients with coronary artery disease (from the Bezafibrate Infarction Prevention Study)

Hyperuricemia appears to be related to metabolic syndrome (MS), but its impact on cardiovascular risk in patients with MS is unclear. We evaluated the impact of hyperuricemia on cardiovascular risk in patients with MS. Of 2,963 patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention study, 1,410 had MS, as established by the presence of ≥3 of the following 5 criteria: serum fasting glucose >110 mg/dl, triglycerides >150 mg/dl, high-density lipoprotein cholesterol <40 mg/dl in men and <50 mg/dl in women, systolic and diastolic blood pressures >130 and 80 mm Hg, respectively, and body mass index >28 kg/m2. The remaining 1,553 patients had no MS. Primary end points were defined as occurrence of acute myocardial infarction or sudden cardiac death. Hyperuricemia was defined as serum uric acid levels >7.0 mg/dl in men and >6.0 mg/dl in women, respectively. Higher rate of primary end point was noted in hyperuricemic patients (n = 284) versus normouricemic patients (n = 1,126) with MS (20.1% and 15.3%, respectively, p = 0.05). After adjustment for age, gender, smoking, diabetes, previous myocardial infarction, hypertension, New York Heart Association classes II to IV, estimated glomerular filtration rate, body mass index, total cholesterol, triglycerides, diuretics, antiplatelets, angiotensin-converting enzyme inhibitors, β blockers, and bezafibrate treatment, hyperuricemic patients with MS demonstrated significantly higher risk for the primary end point compared to normouricemic patients with MS (hazard ratio 1.45, 95% confidence interval 1.00 to 2.17, p = 0.05). In conclusion, hyperuricemia is associated with increased risk of myocardial infarction and sudden cardiac death in patients with MS.     

Clinical significance of high-density lipoprotein cholesterol in patients with low low-density lipoprotein cholesterol.

OBJECTIVES: We sought to evaluate the significance of high-density lipoprotein cholesterol (HDL-C) in the context of low low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Earlier studies support an inverse correlation between circulating HDL-C and coronary risk in patients with normal or elevated LDL-C. METHODS: This study involved 4,188 patients attending the Palo Alto Veterans Administration Medical Center or affiliated clinics with LDL-C levels below 60 mg/dl. Outcomes were examined 1 year after the index LDL-C date. The combined primary end point was myocardial injury or hospitalization from ischemic heart disease. The secondary end point was all-cause mortality. RESULTS: Mean HDL-C levels (mg/dl) by quartile (Q) were: Q1 28 mg/dl, Q2 36 mg/dl, Q3 43 mg/dl, and Q4 63 mg/dl. The rate of myocardial injury or hospitalization for ischemic heart disease showed an inverse relationship to HDL-C (adjusted odds ratios: Q1 1.59 [95% confidence interval (CI) 1.16 to 2.19], Q2 1.39 [95% CI 1.01 to 1.92], Q3 1.33 [95% CI 0.96 to 1.84], and Q4 reference) that persisted regardless of statin use or recent myocardial injury. Analyzing HDL-C as a continuous variable revealed a 10% [95% CI 3% to 17%] increase in the combined end point of myocardial injury or hospitalization for ischemic heart disease for every 10-mg/dl decrease in HDL-C. The unadjusted and adjusted incidence of all-cause mortality demonstrated a U-shaped relationship to HDL-C (adjusted odds ratios: Q1 1.13 [95% CI 0.79 to 1.62], Q2 0.97 [95% CI 0.67 to 1.40], Q3 0.74 [95% CI 0.50 to 1.09], and Q4 reference). CONCLUSIONS: The inverse relationship between HDL-C and coronary risk persists even among patients with LDL-C below 60 mg/dl, although a U-shaped relationship is observed between HDL-C and all-cause mortality.     

Relation of plasma lipoprotein levels with low-grade inflammation in white men without clinical evidence of myocardial ischemia

There is a growing body of evidence indicating that high triglyceride levels are an independent risk factor for cardiovascular disease (CVD) events. In this study we compared the association of fasting levels of non-high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, and triglycerides with white blood cell (WBC) count, an inflammatory marker associated with an adverse CVD prognosis. We studied 458 asymptomatic men (46.0 +/- 7.0 years old) who presented for CVD risk stratification. WBC count (x10(9) cells/L) increased significantly across increasing tertiles of triglyceride level (tertile 1, 6.04 +/- 1.49; tertile 2 6.21 +/- 1.44; tertile 3 6.78 +/- 1.73, p <0.0001), whereas a trend of lower WBC counts was observed across increasing tertiles of HDL cholesterol (tertile 1, 6.52 +/- 1.62; tertile 2, 6.24 +/- 1.50; tertile 3, 6.21 +/- 1.61, p = 0.08). In models adjusted for age, gender, and CVD risk factor, the odds ratio for a high WBC count (quartile > or =4 vs lower 3 quartiles) was significantly higher with increasing levels of triglyceride (2.4, 95% confidence interval 1.3 to 4.8, p = 0.02). When all lipid variables were introduced in the models in addition to traditional CVD risk factors, the association between plasma triglyceride level and WBC count persisted (p = 0.04), which was not found for other lipid parameters. In conclusion, in our study, only plasma triglyceride level was independently associated with a higher WBC count.     

HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men

BACKGROUND. We investigated the association of cholesterol concentrations in serum high density lipoprotein (HDL) and its subfractions HDL2 and HDL3 with the risk of acute myocardial infarction in 1,799 randomly selected men 42, 48, 54, or 60 years old. METHODS AND RESULTS. Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study were done during 1984-1987. In Cox multivariate survival models adjusted for age and examination year, serum HDL cholesterol of less than 1.09 mmol/l (42 mg/dl) was associated with a 3.3-fold risk of acute myocardial infarction (95% confidence intervals [CI], 1.7-6.4), serum HDL2, cholesterol of less than 0.65 mmol/l (25 mg/dl) was associated with a 4.0-fold risk of acute myocardial infarction (95% CI, 1.9-8.3), and serum HDL3 cholesterol of less than 0.40 mmol/l (15 mg/dl) was associated with a 2.0-fold (95% CI, 1.1-4.0) risk of acute myocardial infarction. Adjustments for obesity, ischemic heart disease, other cardiovascular disease, maximal oxygen uptake, systolic blood pressure, antihypertensive medication, serum low density lipoprotein cholesterol, and triglyceride concentrations reduced the excess risks associated with serum HDL, HDL2, and HDL3 cholesterol in the lowest quartiles by 52%, 48%, and 41%, respectively. Additional adjustments for alcohol consumption, cigarettes smoked daily, smoking years, and leisure time energy expenditure reduced these excess risks associated with low HDL, HDL2, and HDL3 cholesterol levels by another 26%, 24% and 21%, respectively. CONCLUSIONS. Our data confirm that both total HDL and HDL2 levels have inverse associations with the risk of acute myocardial infarction and may thus be protective factors in ischemic heart disease, whereas the role of HDL3 remains equivocal.