Quartile Of Low-density Lipoprotein Cholesterol Research Articles

Abstract 14242: The Potential Impact of Inflammation on the Lipid Paradox in Patients With Acute Myocardial Infarction: A Multicenter Study

Introduction: Low-density lipoprotein cholesterol (LDL-C) is a well-recognized risk factor for cardiovascular diseases. However, several clinical studies demonstrated that LDL-C was inversely associated with mortality risk in patients with acute myocardial infarction (AMI), which is known as lipid paradox. Aims: To verify the association between LDL-C and mortality risk among AMI patients. Methods: A total of 5,358 patients with AMI from a nationwide cohort were included in our analysis. All individuals were stratified according to LDL-C quartiles (≤2.00 mmol/l, 2.00-2.54 mmol/l, 2.54-3.19 mmol/l, >3.19 mmol/l) and hsCRP levels (hsCRP≤3 mg/l & hsCRP>3 mg/l). Primary outcome was cardiac mortality. Secondary endpoint was all-cause mortality. Results: During a median follow-up of 2.1 years, 297 deaths and 227 cardiac deaths occurred. Patients in the lowest LDL-C quartile experienced the highest incidence of cardiac and all-cause mortality. The association between mortality risk and LDL-C levels appeared to be U-shaped. Patients in the highest LDL-C quartile had increased incidences of cardiac and all-cause mortality in patients with hsCRP≤3 mg/l. However, higher incidences of both cardiac and all-cause mortality were observed in the lowest LDL-C quartile group among those with hsCRP>3 mg/l. Multivariable COX regression analysis demonstrated that compared with the lowest quartile, the highest LDL-C quartile was significantly associated with a higher risk of cardiac mortality in patients with hsCRP≤3 mg/l (HR 3.04, 95%CI 1.33-6.96, p=0.008), but in patients with hsCRP>3 mg/l, the other three LDL-C quartiles showed a trend for lower cardiac mortality risks, and the second LDL-C quartile met the statistical significance (HR 0.62, 95%CI 0.40-0.95, p=0.027). Conclusion: AMI patients with lower LDL-C levels had a higher risk of mortality. However, this association was only observed in those with high inflammation risk.

Paradoxical association between lipid levels and incident atrial fibrillation according to statin usage

Abstract Background In epidemiology studies, a higher level of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) is associated with a lower risk of atrial fibrillation (AF). Statin use might exert possible confounding effects in the paradoxical relationship; however, the inverse link between AF and cholesterol level that distinguishes statin users from non-users has not been evaluated. Objective We investigated the epidemiological relationships of TC–AF and LDL-C–AF in statin users and non-users, respectively. Methods From the Korean National Health Insurance Service database, we included 9,778,014 adults who underwent a health examination in 2009 and had no prior AF history. The levels of TC and LCL-C at the health exam were categorized in quartile (Q) and decile (D) values of the total study population. The study population was grouped into statin users and non-users, and TC–AF and LDL-C–AF relationships were evaluated. Results 867,336 (8.9%) were on statin use among the total population. Statin users showed higher TC level (208.4±55.6 vs. 194.1±39.5 mg/dL, p<0.001) and LDL-C level (123.0±102.2 vs. 121.3±226.3, p<0.001) compared to non-users. Inverse associations of TC–AF and LCL-C–AF were observed; higher levels of TC and LDL-C were associated with a lower risk of AF. The hazard ratios (HR) and 95% confidence intervals (CI) were 0.797 (0.786–0.809) for the highest quartile of TC (Q4, TC ≥218) and 0.832 (0.82–0.843) for the highest quartile of LDL-C (Q4, LDL-C ≥135) when adjusted by age, sex, lifestyle behaviors, comorbidities, and low-income status. Statin users exhibited higher AF incidence rate than non-statin users, but the association in statin users generally tracked that seen among non-statin users demonstrating similar HR in Q4 of TC [0.812 (0.790–0.835) for statin users and 0.812 (0.798–0.826) for non-statin users] and LDL-C [0.842 (0.819–0.865) for statin users and 0.849 (0.835–0.863) for non-statin users]. Conclusion The paradoxical relationship between lipid levels (TC and LDL-C) and incident AF remained consistent both in statin users and non-users. Further research is required to investigate an underlying mechanism for the cholesterol paradox of AF which still seems evident despite the pleiotropic effects of statin. Funding Acknowledgement Type of funding sources: None.

Blood lipid levels and all-cause mortality in older adults: the Chinese Longitudinal Healthy Longevity Survey 2008-2018.

Proper blood lipid levels are essential for survival in older adults, but inconsistent relationships have been reported between blood lipids and all-cause mortality in the elderly. This retrospective longitudinal study analyzed data from 1,067 Chinese older adults enrolled in the Chinese Longitudinal Healthy Longevity Survey collected in 2008 and followed up until death or December 31, 2018. The outcome was all-cause mortality. Multivariate Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with stratification by age (60-80, 80-100, or ≥100 years) for further analysis. The survival probability according to lipid profile quartiles was calculated using Kaplan-Meier curves and the log-rank test. The participants' mean age was 84.84 years, and 57.0% were female. In total, 578 individuals died, and 277 were lost to follow-up. The mean total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were higher among those who died than among those who survived. Participants in the second HDL-C quartile and the highest LDL-C and triglyceride (TG) quartiles had 28% higher, 23% lower, and 49% lower risks of all-cause mortality, respectively. After further adjustment, the associations remained except for HDL-C, and additional associations were observed between all-cause mortality and the third TC and LDL-C quartiles and the second TG quartile (HR, 1.44; 95% CI, 1.01 to 2.06; HR, 0.68; 95% CI, 0.49 to 0.94; HR, 0.79; 95% CI, 0.62 to 0.99, respectively). Older adults should maintain an LDL-C level of 1.91-2.47 mmol/L and a TG level of no less than 1.66 mmol/L.

Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial.

In epidemiologic cohorts initiated >30 years ago, inflammatory biomarkers, such as interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were shown to independently predict future cardiovascular events with a magnitude of effect comparable to that of low-density lipoprotein cholesterol (LDLC). Whether aggressive contemporary therapy for atherosclerosis has altered these relationships is unknown yet has major implications for future drug development. Interleukin-6, hsCRP, and LDLC were measured at baseline in up to 4168 North American patients enrolled in the contemporary Cardiovascular Inflammation Reduction Trial with prior myocardial infarction or multivessel coronary disease who additionally had diabetes or metabolic syndrome and were followed for a period of up to 5 years for incident major recurrent cardiovascular events and all-cause mortality. Three-quarters of the cohort were previously revascularized and the great majority was taking statins, angiotensin blocking agents, beta-blockers, and antithrombotic agents. Participants were randomly allocated to low-dose methotrexate 15 mg weekly or to placebo. Randomized use of methotrexate had no effect on event rates nor plasma levels of IL-6, hsCRP, or LDL over time. Yet, baseline levels of IL-6, hsCRP, and LDLC were all predictors of major recurrent cardiovascular events; adjusted hazard ratios [HR; 95% confidence interval (CI)] for the lowest to highest baseline quartiles of IL-6 were 1.0 (referent), 1.66 (1.18-2.35), 1.92 (1.36-2.70), and 2.11 (1.49-2.99; P < 0.0001), while adjusted HRs for increasing quartiles of hsCRP were 1.0 (referent), 1.28 (0.92-1.79), 1.73 (1.25-2.38), and 1.79 (1.28-2.50; P < 0.0001) and adjusted HRs for increasing quartiles of LDLC were 1.0 (referent), 1.12 (0.78-1.62), 1.25 (0.87-1.79), and 2.38 (1.72-3.30; P < 0.0001). Effect estimates were not statistically different in these analyses for comparisons between IL-6, hsCRP, or LDLC, although IL-6 was the strongest predictor of all-cause mortality. The highest absolute risks were observed among those with elevated levels of both cholesterol and inflammation [HR 6.4 (95% CI 2.9-14.1) for those in the top quartiles of baseline IL-6 and LDLC, HR 4.9 (95% CI 2.6-9.4) for those in the top quartiles of baseline hsCRP and LDLC, both P < 0.0001]. Despite aggressive contemporary secondary prevention efforts, the relationships between inflammation, cholesterol, and cardiovascular risk are largely unchanged from those described two decades ago. These data are consistent with the hypothesis that future treatments for atherosclerosis may require a combination of inflammation inhibition and additional cholesterol reduction. ClinicalTrials.gov NCT01594333.

P819Post-procedural cholesterol and inflammatory risk in acute myocardial infarction patients undergoing percutaneous coronary intervention

Abstract Objective This study sought to depict the combined association of post-procedural cholesterol and inflammatory risk with clinical outcomes among acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) and pick out patients with highest comprehensive risk. Methods A total of 4802 AMI-PCI patients were divided into quartiles according to post-procedural low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP) level respectively and in combinations for risk analysis. Univariate and adjusted multivariate analysis with Cox model were performed. Hazard ratio (HR) for short-term (90 days) and long-term (1 year) were compared for major adverse cardiovascular events (MACE), including cardiac death, recurrent myocardial infarction and ischemic stroke. Results A significant change in the hazards of 90-day MACE was seen among patients in the highest quartile of post-procedural LDL-C [HR: 0.526 (0.291, 0.951), p=0.034] and highest quartile of CRP [HR: 2.119 (1.150, 3.920), p=0.016]. For 1-year outcomes, only a trend for increasing risk was seen in patients with higher post-procedural CRP (p-trend = 0.016). Combination analysis for cholesterol/inflammatory risk showed that patients lying simultaneously in the lowest quartile of LDL-C and highest quartile of CRP gained the highest risk in the 90-day [HR: 3.16 (1.124, 8.886), p=0.029] and 1-year [HR: 2.515 (1.153, 5.486), p=0.020] follow up. Hazard ratios (HR) for short-term (90 days) and long-term (1 year) primary outcomes according to cholesterol and inflammatory risk 90 days 1 year Type of risk Unadjusted HR (95% CI) P value Adjusted HR (95% CI) P value P for trend Unadjusted HR (95% CI) P value Adjusted HR (95% CI) P value P for trend LDL, mmol/L Quartile 2 0.742 (0.441, 1,248) 0.260 0.663 (0.390, 1.125) 0.128 0.033 0.722 (0.364, 1.125) 0.150 0.683 (0.435, 1.072) 0.097 0.251 Quartile 3 0.653 (0.381, 1.121) 0.122 0.597 (0.344, 1.038) 0.068 0.850 (0.557, 1.229) 0.453 0.850 (0.550, 1.312) 0.462 Quartile 4 0.517 (0.288, 0.928) 0.027 0.526 (0.291, 0.951) 0.034 0.673 (0.427, 1.061) 0.088 0.708 (0.444, 1.131) 0.149 CRP, mg/L Quartile 2 1.365 (0.717, 2.599) 0.334 1.295 (0.654, 2.522) 0.448 0.007 1.063 (0.656, 1.722) 0.805 0.998 (0.608, 1.636) 0.992 0.016 Quartile 3 1.306 (0.681, 2.502) 0.442 1.279 (0.654, 2.499) 0.472 0.999 (0.612, 1.630) 0.996 0.968 (0.586, 1.597) 0.897 Quartile 4 2.354 (1.312, 4.221) 0.004 2.119 (1.150, 3.920) 0.016 1.657 (1.069, 2.570) 0.024 1.528 (0.967, 2.413) 0.069 Multivariate analysis was adjusted for age, sex and traditional cardiovascular risk factors. Combined cholesterol/inflammatory risk Conclusion AMI-PCI patients with lower post-procedural LDL-C and higher CRP might encounter greater cardiovascular risk. Patients with the lowest LDL-C and highest CRP gained extremely high risk and required special attention.

Peritonitis Affects the Relationship Between Low-Density Lipoprotein Cholesterol and Cardiovascular Events in Peritoneal Dialysis Patients

BackgroundIn peritoneal dialysis (PD), the relationship among low-density lipoprotein cholesterol (LDL-C), peritonitis, and cardiovascular (CV) disease has not been clarified. This study was performed to explore their associations in a large PD cohort. MethodsThis retrospective cohort study included incident patients who received PD catheter insertion in our centre. The primary outcome was the first CV event (nonfatal myocardial infarction, CV death, non-haemorrhagic stroke, or any arterial revascularization procedure). Secondary outcomes were the occurrence of peritonitis, CV mortality, and all-cause mortality. ResultsThis study included 1294 patients, whose mean age was 48.1 years. After adjustment for confounders in negative binomial regression models, lower LDL-C quartiles were independently associated with a higher risk of peritonitis, compared with the highest quartile. The multivariate competing risk model showed no significant association between baseline LDL-C and the first CV event in the overall population. However, stratified analysis showed that each 1 mmol/L increase in LDL-C was independently associated with a 21% (subdistribution hazard ratio: 1.21, 95% confidence interval: 1.06-1.39) increased risk of the first CV event among peritonitis-free patients, and with a 20% (subdistribution hazard ratio: 0.80, 95% confidence interval: 0.65-0.99) decreased risk among patients with peritonitis. Moderating-effect analysis showed that the presence of peritonitis significantly influenced the relationships between LDL-C and CV events (P < 0.001). Similar results were also observed in the relationship between LDL-C and mortality. ConclusionsPD patients with lower baseline LDL-C had a higher risk of peritonitis. The effect of LDL-C on CV events and mortality was different by the presence of peritonitis events.

Cholesterol levels and long-term rates of community-acquired sepsis.

BackgroundDyslipidemia is a risk factor for cardiovascular disease, with elevated low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C) recognized as risk factors for acute coronary events. Studies suggest an association between low cholesterol levels and poor outcomes in acute sepsis. We sought to determine the relationship between baseline cholesterol levels and long-term rates of sepsis.MethodsWe used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, a population-based cohort of 30,239 community-dwelling adults. The primary outcome was first sepsis event, defined as hospitalization for an infection with the presence of ≥2 systemic inflammatory response syndrome criteria (abnormal temperature, heart rate, respiratory rate, white blood cell count) during the first 28 hours of hospitalization. Cox models assessed the association between quartiles of HDL-C or LDL-C and first sepsis event, adjusted for participant demographics, health behaviors, chronic medical conditions, and biomarkers.ResultsWe included 29,690 subjects with available baseline HDL-C and LDL-C. There were 3423 hospitalizations for serious infections, with 1845 total sepsis events among 1526 individuals. Serum HDL-C quartile was not associated with long-term rates of sepsis (hazard ratio (HR) (95% CI): Q1 (HDL-C 5–40 mg/dl), 1.08 (0.91–1.28); Q2 (HDL-C 41–49 mg/dl), 1.06 (0.90–1.26); Q3 (HDL-C 50–61 mg/dl), 1.04 (0.89–1.23); Q4, reference). However, compared with the highest quartile of LDL-C, low LDL-C was associated with higher rates of sepsis (Q1 (LDL-C 3–89 mg/dl), 1.30 (1.10–1.52); Q2 (LDL-C 90–111 mg/dl), 1.24 (1.06–1.47); Q3 (LDL-C 112–135 mg/dl), 1.07 (0.91–1.26); Q4, reference).ConclusionLow LDL-C was associated with higher long-terms rates of community-acquired sepsis. HDL-C level was not associated with long-term sepsis rates.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1579-8) contains supplementary material, which is available to authorized users.

Increased levels of low-density lipoprotein cholesterol within the normal range as a risk factor for nonalcoholic fatty liver disease.

ObjectivesDyslipidemia exists within the setting of NAFLD and the relationship of a normal level of low-density lipoprotein cholesterol (LDL-c) with NAFLD is largely unknown. This large population-based study aimed to investigate the association between LDL-c levels within the normal range and the incidence of NAFLD.MethodsA total of 60527 subjects from 2 medical centers who had undergone liver ultrasonography were initially enrolled into this study. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver disease. Subjects were divided into 4 groups (Q1 to Q4) by normal LDL-c quartiles : Q1: ≤ 2.00, Q2: 2.10-2.35, Q3: 2.36-2.68 and Q4: 2.69-3.12 mmol/L. The odds ratios (OR), hazard ratio (HR) and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of LDL-c, using the Q1 as reference.ResultsThe prevalence rates of NAFLD in a cross-sectional population from Q1 to Q4 were 19.34%, 25.86%, 35.65% and 42.08%, respectively. The OR for NAFLD in the cross-sectional population were 1.31 (95% CI 1.14-1.54), 1.73 (95% CI 1.46-2.04), and 1.82 (95% CI 1.49-2.23), respectively, after adjusting for known confounding variables. The HR for NAFLD in the longitudinal population were 1.23 (95% CI 1.12-1.35), 1.57 (95% CI 1.44-1.72) and 2.02 (95% CI 1.86-2.21), compared with Q1. Subjects with higher LDL-c level within the normal range had an increased cumulative incidence rate of NAFLD.ConclusionsIncreased levels of LDL-c within the normal range may play a significant role in the prevalence and incidence of NAFLD, independent of other confounding factors.

Association of Serum Lipids and Coronary Heart Disease in Contemporary Observational Studies.

The use of statins increased among US adults with high coronary heart disease (CHD) risk after publication of the 2001 cholesterol treatment guidelines. We analyzed the association between lipids and CHD among 9578 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants and 346,595 Kaiser Permanente Southern California (KPSC) members with baseline lipid measurements in 2003 to 2007. We performed the same analyses among 14,590 Atherosclerosis Risk In Communities (ARIC) study participants with lipid measurements in 1987 to 1989. Analyses were restricted to blacks and whites 45 to 64 years of age without CHD who were not taking statins at baseline. Total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured at baseline. Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and ratios of total to high-density lipoprotein cholesterol and triglycerides to high-density lipoprotein cholesterol were calculated. The prevalence of diabetes mellitus, history of stroke, and antihypertensive medication use increased at higher low-density lipoprotein cholesterol in ARIC but not in REGARDS or KPSC. Over 8.9 years of follow-up, 225 CHD events occurred in REGARDS, 6547 events in KPSC, and 583 events in ARIC. After multivariable adjustment, less favorable lipid levels were associated with higher hazard ratios for CHD in ARIC. These associations were attenuated in REGARDS and KPSC. For example, the hazard ratio associated with the highest versus lowest quartile of low-density lipoprotein cholesterol (≥ 146 versus ≤ 102 mg/dL) was 1.89 (95% confidence interval, 1.42-2.51) in ARIC, 1.25 (95% confidence interval, 0.81-1.92) in REGARDS, and 1.49 (95% confidence interval, 1.38-1.61) in KPSC. The association between lipids and CHD in contemporary studies may be attenuated by the preferential use of statins by high-risk individuals.

Circulating non–HDL-C levels were more relevant to atherogenic lipoprotein subfractions compared with LDL-C in patients with stable coronary artery disease

Conflicting results have been yielded as to whether low-density lipoprotein (LDL) cholesterol (LDL-C) or non-high-density lipoprotein (HDL) cholesterol (non-HDL-C) is a better marker of coronary artery disease (CAD) risk. Recently, plasma LDL and HDL subfractions have been suggested to be more accurately reflecting the lipoproteins' atherogenicity. We sought to compare the relationship between LDL-C or non-HDL-C and lipoprotein subfractions. We conducted a cross-sectional study in 351 consecutive stable CAD patients without lipid-lowering therapy. The LDL and HDL separations were performed using the Lipoprint System. The LDL-C levels were measured directly, and the non-HDL-C levels were calculated. The cholesterol concentrations of LDL (large, medium, and small) and HDL (small) particles were increased (all P<.001) by non-HDL-C or LDL-C quartiles, whereas the mean LDL particle size and cholesterol concentrations of HDL (large) were decreased (both P<.001) by non-HDL-C quartiles. In age- and gender-adjusted analysis, the cholesterol in small LDL was much strongly related to non-HDL-C than to LDL-C (r=0.539 vs 0.397, both P<.001). Meanwhile, the mean LDL particle size was more closely associated with non-HDL-C than LDL-C (r=-0.336 vs r=-0.136, both P<.05). Significantly, the cholesterol in large HDL was negatively correlated with non-HDL-C (r=-0223, P<.001) but not with LDL-C. These correlations were further confirmed by the fully adjusted multivariable linear regression analysis. Non-HDL-C, in comparison to LDL-C, was more relevant to atherogenic lipoprotein subfractions in patients with stable CAD, supporting that it may be better in assessing cardiovascular risk.

Relationship Between Serum Low-Density Lipoprotein Cholesterol and In-hospital Mortality Following Acute Myocardial Infarction (The Lipid Paradox)

Lipoprotein levels are currently recognized as independent risk factors for long-term cardiovascular events after acute myocardial infarction (AMI). During the acute-phase reaction after AMI, previous studies have reported trends of decreased low-density lipoprotein cholesterol (LDL-C), increased triglycerides, and variable high-density lipoprotein cholesterol (HDL-C) levels. However, the association between LDL-C and HDL-C levels and in-hospital mortality has not been well established following AMI. The relationship between lipid levels and in-hospital all-cause mortality in 115,492 patients hospitalized for AMI (July 2002 to December 2006), registered in the National Registry of Myocardial Infarction (NRMI) 4b-5, was evaluated using multivariable-adjusted logistic regression models. Mean LDL-C was 104 ± 38, HDL-C was 41 ± 14, and triglycerides 143 ± 83 mg/dl. Compared with the lowest quartile of LDL-C (<77mg/dl), the risk of in-hospital mortality in the second to fourth quartiles was decreased (adjusted odds ratio 0.79, 0.80, and 0.85, respectively). For HDL-C, only those in the lowest quartile (<31mg/dl) had higher risk of in-hospital mortality (odds ratio 1.20) compared with the highest quartile (≥47mg/dl). Results from NRMI 4b-5 suggest a lipid paradox, with lower LDL-C levels associated with increased risk of in-hospital mortality, contrary to findings outside the acute setting. Consistent with previous analyses, lowest HDL-C levels were associated with increased in-hospital mortality. In conclusion, further explorations of the relationship between very low levels of LDL-C, myocardial necrosis, and subsequent adverse cardiovascular events are warranted.

Association of low-density lipoprotein cholesterol-related genetic variants with aortic valve calcium and incident aortic stenosis.

Plasma low-density lipoprotein cholesterol (LDL-C) has been associated with aortic stenosis in observational studies; however, randomized trials with cholesterol-lowering therapies in individuals with established valve disease have failed to demonstrate reduced disease progression. To evaluate whether genetic data are consistent with an association between LDL-C, high-density lipoprotein cholesterol (HDL-C), or triglycerides (TG) and aortic valve disease. Using a Mendelian randomization study design, we evaluated whether weighted genetic risk scores (GRSs), a measure of the genetic predisposition to elevations in plasma lipids, constructed using single-nucleotide polymorphisms identified in genome-wide association studies for plasma lipids, were associated with aortic valve disease. We included community-based cohorts participating in the CHARGE consortium (n = 6942), including the Framingham Heart Study (cohort inception to last follow-up: 1971-2013; n = 1295), Multi-Ethnic Study of Atherosclerosis (2000-2012; n = 2527), Age Gene/Environment Study-Reykjavik (2000-2012; n = 3120), and the Malmö Diet and Cancer Study (MDCS, 1991-2010; n = 28,461). Aortic valve calcium quantified by computed tomography in CHARGE and incident aortic stenosis in the MDCS. The prevalence of aortic valve calcium across the 3 CHARGE cohorts was 32% (n = 2245). In the MDCS, over a median follow-up time of 16.1 years, aortic stenosis developed in 17 per 1000 participants (n = 473) and aortic valve replacement for aortic stenosis occurred in 7 per 1000 (n = 205). Plasma LDL-C, but not HDL-C or TG, was significantly associated with incident aortic stenosis (hazard ratio [HR] per mmol/L, 1.28; 95% CI, 1.04-1.57; P = .02; aortic stenosis incidence: 1.3% and 2.4% in lowest and highest LDL-C quartiles, respectively). The LDL-C GRS, but not HDL-C or TG GRS, was significantly associated with presence of aortic valve calcium in CHARGE (odds ratio [OR] per GRS increment, 1.38; 95% CI, 1.09-1.74; P = .007) and with incident aortic stenosis in MDCS (HR per GRS increment, 2.78; 95% CI, 1.22-6.37; P = .02; aortic stenosis incidence: 1.9% and 2.6% in lowest and highest GRS quartiles, respectively). In sensitivity analyses excluding variants weakly associated with HDL-C or TG, the LDL-C GRS remained associated with aortic valve calcium (P = .03) and aortic stenosis (P = .009). In instrumental variable analysis, LDL-C was associated with an increase in the risk of incident aortic stenosis (HR per mmol/L, 1.51; 95% CI, 1.07-2.14; P = .02). Genetic predisposition to elevated LDL-C was associated with presence of aortic valve calcium and incidence of aortic stenosis, providing evidence supportive of a causal association between LDL-C and aortic valve disease. Whether earlier intervention to reduce LDL-C could prevent aortic valve disease merits further investigation.

LDL cholesterol as a novel risk factor for contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention

Background: Low density lipoprotein cholesterol (LDL-C) is associated with endothelial dysfunction, inflammation and increased vasoconstriction, which are involved in the development of contrast-induced acute kidney injury (CI-AKI). However, whether LDL-C is an independent risk factor of CI-AKI in patients undergoing percutaneous coronary intervention (PCI) is unknown. Methods: We prospectively enrolled 3236 consecutive patients undergoing PCI between January 2010 and September 2012. Multivariate logistic regression analysis was used to determine whether LDL-C is an independent risk factor of CI-AKI. CI-AKI was defined as an absolute increase in serum creatinine of ≥0.5 mg/dL or ≥25% over the baseline value within 48–72 h after contrast exposure. Results: CI-AKI was observed in 338 patients (10.4%). Patients with CI-AKI had a significantly higher rate of in hospital mortality (4.4% vs. 0.5%, p < 0.001), and significantly higher rates of other in hospital complications compared with those without CI-AKI. The LDL-C quartiles were as follows: Q1 (<2.04 mmol/L), Q2 (2.04–2.61 mmol/L), Q3 (2.61–3.21 mmol/L) and Q4 (>3.21 mmol/L). Patients with high baseline LDL-C levels were more likely to develop CI-AKI and composite end points including all-cause mortality, renal replacement therapy, non-fatal myocardial infarction, acute heart failure, target vessel revascularization or cerebrovascular accident during the observation period of hospitalization (8.9%, 9.9%, 10.5%, 12.6%, p = 0.001, and 5.0%, 5.2%, 6.1%, 8.1%, respectively; p = 0.007). Univariate logistic analysis showed that LDL-C levels (increment 1 mmol/L) were significantly associated with CI-AKI (odds ratio = 1.25, 95% confidence interval (CI), 1.11–1.39, p < 0.001). Furthermore, LDL-C remained a significant risk factor of CI-AKI (odds ratio = 1.23, 95% CI, 1.04–1.45, p = 0.014), even after adjusting for potential confounding risk factors. Conclusions: Measurement of plasma LDL-C concentrations in patients undergoing PCI may be helpful to identify those who are at risk of CI-AKI and poor in hospital outcomes.

Low-density lipoprotein cholesterol and metabolic syndrome in an Iranian high-risk population

AimCurrently, one study support the hypothesis that low-density lipoprotein cholesterol (LDLC) is associated with metabolic syndrome (MetS) independent of pre-existing components of MetS. In this study we further evaluated the ability of the LDLC to predict prevalence and incidence of MetS in an Iranian high-risk population. Materials and methodsWe analyzed baseline (n=3396) and 7-year follow-up data (n=865) in first-degree relatives (FDR) of consecutive patients with type 2 diabetes 30–70 years old. We used logistic regression to estimate the odds ratio (OR) for prevalent MetS, and Cox proportional hazard models to estimate hazard ratio (HR) for incident MetS across quartiles of LDLC and plotted a receiver operating characteristic (ROC) curve to assess discrimination. ResultsThe highest quartile of LDLC compared with the lowest quartile was associated with MetS in both the prevalent (OR 1.39, 95% CI 1.13, 1.70) and incident in unadjusted models (HR 1.24, 95% CI 1.03, 1.49). Adjusted for age, gender and pre-existing components of MetS attenuated association for both prevalent (OR 1.15, 95% CI 0.83, 1.59) and incident MetS (HR 1.13, 95% CI 0.93, 1.38). The area under the ROC was 52.8% (95% CI 50.7, 55.0) for prevalent and 51.8% (95% CI 47.2, 56.3) for incident MetS. ConclusionThe results of this study highlight that LDLC level is not a robust predictor of MetS, independent of age, gender or the pre-existing components of MetS, in high-risk individuals in Iran.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Low-density Lipoprotein Cholesterol is a Predictor of Metabolic Syndrome in a Japanese Health Screening Population

Both increased serum levels of low-density lipoprotein cholesterol (LDLC) and metabolic syndrome (MetS) are associated with obesity and have been established to be risk factors of cardiovascular disease. However, studies on the relationship between LDLC and MetS have been limited. Cross-sectional (n=3,871) and longitudinal (n=2,558) associations between LDLC and MetS were examined in a Japanese health screening population. The odds ratio (OR) [95% confidence interval (CI)] of coexisting MetS for each one SD increase in the LDLC level was 1.25 [1.12-1.40] (p<0.001) adjusted for body mass index (BMI) and other confounding covariates and 1.12 [0.97-1.28] (p=0.119) adjusted for numerical values of the components of MetS and other confounding covariates. The similarly adjusted ORs [95% CIs] for the highest quartile of LDLC (Q4) compared with the lowest quartile (Q1) were 1.76 [1.22-2.54] (p=0.002) and 1.46 (0.93-2.30) (p=0.101), respectively. The hazard ratio (HR) [95% CI] for developing MetS for each one SD increase in the LDLC level was 1.24 [1.10-1.40] (p<0.001) adjusted for BMI and other confounding covariates and 1.19 [1.05-1.34] (p=0.006) adjusted for the pre-existing dichotomous five components of MetS and other confounding covariates. The similarly adjusted HRs [95% CIs] for developing MetS for Q4 compared with Q1 were 1.71 [1.17-2.51] (p=0.006) and 1.61 [1.08-2.40] (p=0.020), respectively. The LDLC level is associated with coexisting MetS and functions as a predictor of the development of MetS, independent of BMI or the pre-existing components of MetS, in a Japanese health screening population.

Abstract 8706: Impact of Small Dense Low-Density Lipoproteins Cholesterol on Cardiovascular Disease in an Urban Japanese Cohort: The Suita Study

Aim: Increased plasma low-density lipoprotein cholesterol (LDL-C) concentrations have been shown to be one of the major risk factors for cardiovascular disease (CVD). Clinical evidence also indicates that small dense LDL (sd-LDL) particles are more atherogenic than large buoyant LDL particles. Because there was no easy assay to measure the amount of sd-LDL-C, few studies have addressed the association between sd-LDL-C and CVD. In this study, we hypothesized that higher sd-LDL-C is associated with increased risk for CVD. To this end, we examined the association between sd-LDL-C and CVD in Japanese by using a new kit to measure sd-LDL-C. Methods: We studied 2034 Japanese individuals (30 to 79 years old without stroke or coronary heart disease (CHD)) in the Suita Study, who completed measurement of direct LDL-C and sd-LDL-C by a kit based on the precipitation method with filtration, and then followed for 11.7 years on average. We calculated the Cox proportional adjusted hazard ratios (HRs) of LDL-C, sd-LDL-C, and sd-LDL-C/LDL-C ratio quartiles for incident CAD, stroke, and CVD (CHD + stroke) adjusting for age, sex, body mass index, diabetes, blood pressure category (defined on the basis of the ESH-ESC 2007 criteria), smoking and drinking at baseline. Results: The mean age of this cohort was 59.3 years old and 52.4% was women. The HR of the 4th quartile of sd-LDL-C for the development of CAD was 3.35 (95% confidence intervals: 1.38 to 8.13), which was higher than that in the analysis using LDL-C quartiles. In multivariable adjustment, the HR of the 4th quartile was almost similar. When we used the quartiles of sd-LDL/LDL ratio, increased sd-LDL/LDL ratio was associated with the incidence of CVD, CAD, and stroke. Sex-specific analysis showed that the association of sd-LDL-C with CAD and CVD was statistically significant in men, but not in women. Conclusions: We demonstrated that increased levels of sd-LDL-C are significantly associated with the development of CVD. Our data indicate that sd-LDL-C is a better risk factor for CVD than LDL-C for risk assessment.

The Complex Relationship Between Cholesterol and Brain Hemorrhage

In this issue of Circulation , Noda et al1 report an association between low levels of low-density lipoprotein cholesterol (LDL-C) and an increase in the risk of fatal intraparenchymal intracerebral hemorrhage in a Japanese population-based cohort. The relationship between lipid levels and stroke is complex. The Prospective Studies Collaboration conducted a meta-analysis evaluating the association between blood cholesterol and vascular mortality based on data from 61 prospective cohort studies including nearly 900 000 persons free of vascular disease at baseline (11.6 million person-years at risk).2 Lower levels of usual total cholesterol were strongly associated with lower risk of fatal ischemic heart disease; every 1 mmol/L lower cholesterol was associated with a 56% reduction (hazard ratio [HR], 0.44; 95% CI, 0.42 to 0.48) in those 40 to 49 years of age, a 34% reduction (HR, 0.66; 95% CI, 0.65 to 0.68) in those 50 to 69 years of age, and a 17% reduction (HR, 0.83; 95% CI, 0.81 to 0.85) in those 70 to 89 years of age. In contrast to death resulting from ischemic heart disease, there was only a weak relationship between usual total cholesterol and death caused by stroke in those 40 to 59 years of age (HR, 0.90; 95% CI, 0.84 to 0.97 for every 1 mmol/L lower cholesterol) and no relationship for older age groups after accounting for blood pressure. An analysis combing the data for the Prospective Studies Collaboration with data from the Multiple Risk Factors Intervention Trial (MRFIT) also found that lower usual total cholesterol was associated with a lower risk of fatal stroke in those 40 to 49 years of age (HR, 0.87; 95% CI, 0.76 to 1.00 per 1 mmol/L lower total cholesterol), with similar reductions in those 50 to 59 (HR, 0.91; 95% CI, 0.85 to 0.97) and 60 …

Non-HDL cholesterol is strongly associated with coronary artery calcification in asymptomatic individuals

Background Growing evidence shows that non-high-density lipoprotein cholesterol (Non-HDL-C) is a strong and independent predictor of cardiovascular disease (CVD). Few studies have assessed the association between traditional lipid measures and subclinical end points. In this study we analyzed the association of Non-HDL-C, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) with coronary artery calcium (CAC), a marker of subclinical atherosclerosis. Methods The study population consisted of 1611 consecutive asymptomatic individuals (67% men, mean age: 53 ± 10 years) referred to a single electron beam tomography (EBT) facility for CAC screening. Multivariate logistic regression was used to test the association between increasing quartiles of lipid levels and presence of CAC score (CACS) > 0 and CACS ≥ 100, with the lowest levels (first quartile) of lipid values as reference. Results Overall CACS of 0, 1–99, 100–399 and ≥400, were observed in 35%, 44%, 12% and 9% of the study subjects, respectively. The prevalence of CAC increased significantly across increasing quartiles of LDL-C, TG and Non-HDL-C (all p < 0.0001), whereas CACS was significantly lower across increasing quartiles of HDL-C ( p < 0.001). In a multivariate model controlling for age, gender, race, cigarette smoking, hypertension, family history of coronary artery disease and obesity, there was a significant increase in the prevalence of CAC with increasing values of each lipid variable. In a multivariate model simultaneously controlling for increasing quartiles of the remaining lipid variables, only the association of Non-HDL-C with CACS > 0 remained statistically significant ( p = 0.002). Similar results were observed with CACS ≥ 100 ( p = 0.038). Conclusion In this study Non-HDL-C was more strongly associated with subclinical atherosclerosis than all other conventional lipid values. These data suggests that Non-HDL-C may be an important treatment target in primary prevention.

Low‐Density Lipoprotein Cholesterol and Mortality in Older People

To investigate the role of low-density lipoprotein cholesterol (LDL-C) as a predictor of mortality in elderly subjects. Population-based prospective cohort study. Two communities in northern Italy. Three thousand one hundred twenty Caucasian subjects aged 65 and older recruited in for the Cardiovascular Study in the Elderly and followed up for 12 years. Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL-C, glucose, creatinine, and body mass index. Clinical measures: medical assessment, diabetes mellitus, hypertension, stroke, coronary disease, heart failure, and smoking and drinking habits. Vital status measures: death certificates from the Registry Office and causes of death according to the International Classification of Diseases. After plotting mortality rates using quartiles of LDL-C, relative hazard rates (RHRs) were calculated using multivariate Cox regression analyses. When the trend was nonlinear, the RHRs were further calculated for the 25th, 50th, and 75th percentiles of the distribution to confirm curvilinearity. The distribution of risk of total mortality in women and of fatal heart failure in all subjects was curvilinear (non J-shaped), decreasing nonlinearly with LDL-C. For total mortality in men and cardiovascular mortality in both sexes, the relationship with LDL-C was J-shaped. The risk of fatal myocardial infarction was J-shaped in men, whereas it increased linearly with higher LDL-C in women. In both sexes, the association between stroke mortality and LDL-C was not significant. This study adds to the uncertainty of the role of elevated levels of LDL-C as a risk factor for mortality in old people.