Conventional Lipid Measurements Research Articles

FRI181 Increased LDL Particle And Apolipoprotein B Concentrations In Patients With Nonfunctioning And Cortisol Secreting Adrenal Adenomas

Abstract Disclosure: R. Sandooja: None. A. Kittithaworn: None. P. Dogra: None. D. Gruppen: None. E. Atkinson: None. S. Achenbach: None. K. Yu: None. M. Connelly: None. V. Simha: None. R.P. Dullaart: None. I. Bancos: None. INTRODUCTION: Based on the spectrum of cortisol excess, adrenal adenomas are classified as adenomas with Cushing syndrome (CS), adenomas with mild autonomous cortisol secretion (MACS), and non-functioning adenomas (NFA). Patients with adrenal adenomas demonstrate a high prevalence of cardiovascular morbidity and mortality proportional to the degree of hypercortisolism. Evidence on whether dyslipidemia is a contributing cardiovascular risk factor in patients with NFA and MACS is discrepant. We aimed to characterize (apo) lipoprotein abnormalities across the spectrum of cortisol excess in patients with adenomas as compared to referent subjects. METHODS: Study Design: Single center cross sectional study between 01/2015 - 05/2021.Patients: Adults with NFA, MACS, or CS were consecutively enrolled. MACS was diagnosed based on post-dexamethasone cortisol >1.8 mcg/dL. Referent subjects were recruited from local population of patients with available abdominal imaging and no adrenal disorders. All subjects provided fasting ethylenediaminetetraacetic acid (EDTA) venous samples. Measurements: Nuclear magnetic resonance (NMR) spectroscopy measurements included total cholesterol (TC), low-density lipoprotein (LDL) and LDL particle concentrations, high-density lipoprotein (HDL) subclasses, apolipoprotein B (apo B), triglycerides (TG) and TG-rich lipoprotein concentrations. RESULTS: Participants included 101 patients with CS (median age 44 years, IQR 31-58, 85% women), 158 patients with MACS (median age 62 years, IQR 51-70, 62% women), 166 patients with NFA (median age 60 years, IQR 53--66, 63% women) and 136 referent subjects (median age 68 years, IQR 57-77, 52% women). Patients had higher BMI (32 vs 27 kg/m2), higher prevalence of hypertension (72% vs 46%) and diabetes mellitus (27% vs 9%) as compared to reference subjects. Statin therapy was used in 32% of patients and referent subjects. After adjusting for age, sex, BMI, smoking, diabetes, hypertension, and statin therapy, as compared to referent subjects, we found inconsistent increase in TC, LDL cholesterol and TG across CS, MACS and NFA and no consistent differences in LDL size, HDL variables, TG and TG-rich lipoproteins. However, when compared to referent subjects, LDL particle concentrations- CS(OR 1.78, 95% CI 1.33-2.39), MACS (OR 1.31, 95% CI 1.03-1.67), and NFA (OR 1.43, 95% CI 1.12-1.82) and Apo B levels were higher in all patient categories: CS (OR 2.26, 95% CI 1.57-3.24), MACS (OR 1.36 95% CI 1.00-1.85 ), and NFA (OR 1.54 95% CI 1.13-2.09). These differences were particularly evident in patients not on statin therapy. CONCLUSIONS: We found that LDL particle and Apo B concentrations were elevated in all patient groups, including those with MACS and NFA. In comparison to conventional lipid measurements, LDL particle and Apo B may serve as a better biomarker of the future cardiovascular risk in patients with adrenal adenomas. Presentation: Friday, June 16, 2023

Atherogenic lipoprotein profile associated with anthropometric indices of obesity and their association with cardiometabolic risk markers: a cross-sectional study in community

Abstract Background Obesity, especially abdominal fat accumulation, is strongly associated with various metabolic comorbidities. Whether simple anthropometric measures are independently associated with atherogenic lipoproteins is not completely clear. Methods We randomly recruited 505 participants (51.5% women; mean age: 48.8 years) from the Flemish community, who had undergone lipoprotein particle measurements by nuclear magnetic resonance spectroscopy and conventional lipid measurements. Each lipoprotein fraction was subgrouped into large, medium, and small subclass. Anthropometric measures included body mass index (BMI) and waist-to-hip ratio (WHR), and defined BMI obesity as BMI ≥30 kg/m2, and WHR obesity as WHR ≥0.85 (women) or 0.9 (men). Results In the multivariable logistic regression analysis, total very-low-density lipoprotein (VLDL) particle and its subclasses were positively associated with BMI obesity (adjusted odds ratio [OR] for total VLDL: 2.37; 95% confidence interval [CI]: 1.70–3.31) and WHR obesity (OR for total VLDL: 2.06 [95% CI: 1.55–2.73]). The level of total high-density lipoprotein (HDL) particle and its subclass was negatively associated with BMI (OR for total HDL: 0.63 [95% CI: 0.45–0.90), but not with WHR (P≥0.11). None of the low-density lipoprotein (LDL) particles was associated with the two types of obesity (P≥0.092). BMI was inversely associated with the size of LDL and HDL particles, whereas high WHR was significantly associated with smaller VLDL and HDL sizes. For conventional lipid measures, both BMI and WHR were independently associated with high triglyceride and remnant cholesterol, both mainly driven from VLDL particles, and low HDL cholesterol (P≤0.008). These associations were confirmed in multivariable linear regression analysis, except the association of BMI with HDL number and the association of WHR with HDL size. With partial least squares analysis, the lipoprotein profiles of BMI and WHR were significantly associated with a high 10-year cardiovascular disease risk score, the homeostasis model assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein. Conclusion BMI and WHR were independently associated with high triglyceride-rich lipoproteins, decreased HDL cholesterol. The size of LDL and HDL was more consistently associated with BMI than WHR. The lipoprotein alterations may link obesity with high cardiometabolic risk. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The European Research Council; the European Research Area Net for Cardiovascular Diseases

There is a U shaped association between non high density lipoprotein cholesterol with overall and cardiovascular mortality in chronic kidney disease stage 3\u20135

Dyslipidemia is common in patients with chronic kidney disease (CKD), however the relationship between dyslipidemia and mortality in patients with moderate to severe CKD remains controversial. Non-high-density lipoprotein (HDL) cholesterol has been reported to be a more accurate predictor of clinical outcomes than conventional lipid measurements. Hence, the aim of this study was to investigate associations between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3–5. We enrolled 429 pre-dialysis patients with stage 3 to 5 CKD from May 2006 to January 2010. The patients were divided into four groups according to quartiles of non-HDL cholesterol. The patients were followed until death or until January 2020. During a median 11.6 years of follow-up, there were 78 (18.2%) deaths overall and 32 (7.5%) cardiovascular deaths. In adjusted models, the patients in quartile 1 (hazard ratio [HR] 3.368; 95% confidence interval [CI] 1.388–8.176; p = 0.007), quartile 3 (HR 3.666; 95% CI 1.486–9.044; p = 0.005), and quartile 4 (HR 2.868; 95% CI 1.136–7.240; p = 0.026) of non-HDL cholesterol had a higher risk of overall mortality (vs. quartile 2). In addition, the patients in quartile 1 (HR 19.503; 95% CI 2.185–174.0925 p = 0.008), quartile 3 (HR 28.702; 95% CI 2.990–275.559; p = 0.004), and quartile 4 (HR 11.136; 95% CI 1.126–110.108; p = 0.039) had a higher risk of cardiovascular mortality (vs. quartile 2). Our study showed a U-shaped relationship between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3–5. Assessing non-HDL cholesterol may help to identify subjects at high-risk of adverse outcomes.

Circulating metabolomic profile indicates mitochondrial dysfunction in HIV-dyslipidemia

Aim: Dyslipidemia in HIV-infected patients is unique and pathophysiologically associated with host factors, HIV itself and the use of antiretroviral drugs. Even the newer well-tolerated drugs that exert less influence on the lipid profile are still associated with lipid metabolism derangements. The use of nuclear magnetic resonance spectroscopy (NMR) provides additional data to conventional lipid measurements concerning the number of lipoprotein subclasses and particle sizes. In the present study, we investigated the ability of lipoprotein profile, measured by NMR, to predict dyslipidemia onset in treated HIV-infected patients.

Circulating metabolomic profile can predict dyslipidemia in HIV patients undergoing antiretroviral therapy

Background and aimsDyslipidemia in HIV-infected patients is unique and pathophysiologically associated with host factors, HIV itself and the use of antiretroviral therapy (ART). The use of nuclear magnetic resonance spectroscopy (NMR) provides additional data to conventional lipid measurements concerning the number of lipoprotein subclasses and particle sizes. MethodsTo investigate the ability of lipoprotein profile, we used a circulating metabolomic approach in a cohort of 103 ART-naive HIV-infected patients, who were initiating non-nucleoside analogue transcriptase inhibitor (NNRTI)-based ART, and we subsequently followed up these patients for 36 months. Univariate and multivariate analyses were performed to evaluate the predictive power of NMR spectroscopy. ResultsVLDL-metabolism (including VLDL lipid concentrations, sizes, and particle numbers), total triglycerides and lactate levels resulted in good classifiers of dyslipidemia (AUC 0.903). Total particles/HDL-P ratio was significantly higher in ART-associated dyslipidemia compared to ART-normolipidemia (p = 0.001). Large VLDL-Ps were positively associated with both LDL-triglycerides (ρ 0.682, p < 0.001) and lactate concentrations (ρ 0.416, p < 0.001), the last one a marker of mitochondrial low oxidative capacity. ConclusionsOur data suggest that circulating metabolites have better predictive values for HIV/ART-related dyslipidemia onset than do the biochemical markers associated with conventional lipid measurements. NMR identifies changes in VLDL-P, lactate and LDL-TG as potential clinical markers of baseline HIV-dyslipidemia predisposition. Differences in circulating metabolomics, especially differences in particle size, are indicators of important derangements of mitochondrial function that are linked to ART-related dyslipidemia.

Lipoprotein Heterogeneity Early in Pregnancy and Preterm Birth.

Background The concentration and size of lipoprotein particles are associated with race, inflammation, and disease. When triglycerides are high, as in pregnancy, lipoprotein particle size may have physiologic importance beyond conventional lipid measurements. We considered that lipoprotein particles may be related to preterm birth (PTB) and explored race differences. Materials and Methods Samples were collected at 9 weeks' gestation (22 PTB [&lt; 37 weeks]; 42 term births [≥ 37 weeks]). Lipids were assayed using standard techniques. Concentrations of high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein particles (HDL-P, LDL-P, and VLDL-P, respectively) and markers of systemic inflammation were quantified using nuclear magnetic resonance spectroscopy and related to PTB. Results Women with PTB had lower VLDL-P (− 10.66 nmol/L, p = 0.03) and higher systemic inflammation (+ 19.2 µmol/L, p = 0.02) compared with women with term births, independent of race, pre-pregnancy body mass index, and smoking. Black versus white women had lower VLDL-P and higher HDL cholesterol (both p &lt; 0.05). Race-specific results indicated that large HDL-P and inflammation (glycoprotein B) were higher with PTB versus term birth among black women only. Conclusion Women with PTB had lower VLDL-P early in pregnancy, which may represent impaired lipid response. Black–white differences in the lipoprotein profile are similar to nonpregnant adults, but race-specific lipoprotein and inflammation associations with PTB warrant further study.

Validation of a Newly Developed Equation for Estimating Serum Apolipoprotein B: Associations with Cardiovascular Disease Surrogate Markers in Koreans.

PurposeMany clinical guidelines recommend apolipoprotein B (apoB) measurement, particularly in subjects with metabolic syndrome or type 2 diabetes. Recently, we developed a new equation to estimate serum apoB (apoBE). We validated the clinical relevance of apoBE and compared the performance of the equation with conventional lipid measurements and direct measurement of apoB.Materials and MethodsStudy subjects were recruited from patients who visited the Health Screening Center at Kangbuk Samsung Hospital between January and December 2009 for routine medical examinations (n=78125). For analysis of coronary calcium score, we recruited study subjects from the same institution between January 2007 and December 2010 (n=16493).ResultsapoBE was significantly correlated with serum high-sensitivity C-reactive level {r=0.18 [95% confidence interval (CI), 0.18–0.19]} in partial correlation analysis adjusted for age, sex, and body mass index. apoBE was associated with a Framingham risk score indicating more than moderate risk (10-year risk ≥10%), the presence of microalbuminuria, and the presence of coronary artery calcium in multivariate logistic regression analysis. These associations were comparable to those of directly-measured serum apoB [odds ratio per 1 SD 3.02 (2.75–3.27) vs. 2.70 (2.42–3.02) for a Framingham risk score indicating more than moderate risk, 1.31 (1.21–1.41) vs. 1.35 (1.25–1.45) for the presence of microalbuminuria, and 1.33 (1.26–1.41) vs. 1.31 (1.23–1.38) for the presence of coronary calcium score respectively]. These findings were also consistently observed in subgroup analysis for subjects with type 2 diabetes.ConclusionThe associations between cardiovascular surrogate markers and apoBE were comparable to those of directly-measured apoB.

Prediction of future development of cardiovascular disease with an equation to estimate apolipoprotein B: A community-based cohort study.

Apolipoprotein B (apoB) has additional benefits over conventional lipid measurements in predicting future cardiovascular disease (CVD). We aimed to validate the clinical relevance of our equation to estimate apoB in a large-scale, prospective, community-based cohort study (Ansung-Ansan cohort study).A total of 9001 Korean subjects were assessed. We excluded subjects with history of CVD (n = 228), taking lipid-lowering medications (n = 51), and those whose outcome data were not available (n = 33). Finally, a total of 8713 subjects (4126 men and 4587 women) with a mean age of 52.2 years were enrolled and followed up biannually for a mean 8.1 years.At baseline, 24.9% of subjects were current smokers, 12.5% had diabetes, and 22.2% had hypertension. Incident case of CVD occurred in 600 of the study subjects (493 ischemic heart disease and 424 stroke). Independent variables included in the models were age, sex, waist circumference, current smoking, and presence of diabetes and hypertension. Both non-HDL cholesterol (HR per 1-SD [95% CI]; 1.13 [1.05–1.23], P = 0.002) and estimated apoB (HR per 1-SD [95% CI]; 1.14 [1.05–1.24], P = 0.001) were independently associated with the development of CVD; however, the LDL cholesterol level was not predictive of future CVD (HR per 1-SD [95% CI]; 1.07 [0.99–1.16], P = 0.08).Both non-HDL cholesterol and estimated apoB level were independently associated with the development of CVD. Because LDL cholesterol has limited value to predict incident CVD, we recommend calculating non-HDL cholesterol or apoB with our equation to predict risk of incident CVD in the general Korean population.

Large high-density lipoprotein particle number is independently associated with microvascular function in patients with well-controlled low-density lipoprotein concentration: A vasodilator stress magnetic resonance perfusion study

Abnormalities in total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides are associated with microvascular dysfunction. Recent studies suggest that lipid subfractions better predict atherogenic burden than a routine lipid panel. We sought to determine, whether lipid subfractions are more strongly associated with microvascular function and subclinical atherosclerosis, than conventional lipid measurements using vasodilator stress cardiovascular magnetic resonance (CMR). Twenty-four adults referred for risk stratification from a lipid clinic with low-density lipoprotein cholesterol (LDL-C) <100 mg/dL underwent vasodilator CMR. Time-intensity curves generated from stress and rest perfusion images were used to determine the area under the curve (AUC) for the mid-ventricular slice myocardium and the left ventricular (LV) cavity. Myocardial perfusion reserve index (MPRi) was defined as stress to rest ratio of mid-ventricular myocardium AUC, normalized to LV cavity AUC. Lipid panels that included subfractions of LDL and high-density lipoprotein (HDL) were measured using nuclear magnetic resonance testing. The association between MPRi and lipid parameters was examined using univariate linear regression; lipid components statistically correlated with MPRi (P < .05) were then subjected to multivariate analysis. Univariate regression analysis showed MPRi was associated with HDL-C, triglycerides, large HDL-P, and small LDL-P; no association was found between MPRi and total cholesterol, LDL-C, total LDL-P, or total HDL-P. Using multivariate analysis, large HDL-P was independently associated with MPRi. In patients with LDL-C <100 mg/dL, large HDL-P is independently associated with CMR-derived myocardial perfusion reserve, a surrogate for microvascular function and subclinical atherosclerosis. Further studies using lipid subfractions to better understand cardiovascular risks are warranted.

Apolipoprotein B and non-HDL cholesterol are more powerful predictors for incident type 2 diabetes than fasting glucose or glycated hemoglobin in subjects with normal glucose tolerance: a 3.3-year retrospective longitudinal study.

The association between atherogenic dyslipidemia (AD) and incident type 2 diabetes (T2D) in the low-risk group for T2D has not yet been determined. The aims of this study were to investigate whether AD, characterized by increased serum apoB and non-HDL cholesterol, could predict the development of T2D in subjects with normal glucose tolerance (NGT). A total of 84,394 subjects with NGT (48,906 men and 35,488 women), aged 20-89 years (mean age 38.4 years), were enrolled in this study and were followed for a mean duration of 3.3 years. ApoB and non-HDL cholesterol levels showed stronger associations with the development of T2D compared with conventional lipid measurements and their ratios (HR per 1-SD (95 % CI) 1.27 (1.23-1.30) and 1.27 (1.24-1.29), respectively, both P < 0.001). In multivariate Cox regression models, both apoB and non-HDL cholesterol were associated with the development of T2D, independent of other risk factors for T2D, fasting serum glucose, HbA1c, and conventional lipid measurements such as triglycerides and HDL cholesterol (HR per 1-SD (95 % CI) 1.16 (1.11-1.21) and 1.15 (1.11-1.19), respectively, both P < 0.001). However, fasting serum glucose was not associated with the development of T2D in these models. In conclusion, AD was more closely associated with the development of T2D than fasting glucose or glycated hemoglobin in subjects with NGT.

Atherogenic dyslipidaemic profiles associated with the development of Type 2 diabetes: a 3.1‐year longitudinal study

While there is thought to be an association between glucose and lipid metabolism, it is largely unknown whether apolipoproteinB and non-high density lipoprotein (HDL) cholesterol are associated with the development of Type2 diabetes. It is also unknown whether these atherogenic dyslipidaemic profiles have a stronger association with diabetes risk compared with conventional lipid measurements. A total of 118429 subjects without diabetes (70980 men and 47449 women), aged 17-90years (mean age 39.6years), were enrolled in this study and followed for a mean duration of 3.1years. ApolipoproteinB and non-HDL cholesterol levels showed a strong association with the development of Type2 diabetes compared with conventional lipid measurements and their ratios [hazard ratio per 1sd; 1.39 (95%CI 1.37-1.42) and 1.38 (95%CI 1.35-1.40), respectively; both P<0.001]. The Kaplan-Meier survival curve demonstrated that Type2 diabetes developed more frequently as apolipoproteinB or non-HDL cholesterol levels increased across quartiles (both P<0.001). In multivariate Cox regression analyses, both apolipoproteinB and non-HDL cholesterol were associated with the development of Type2 diabetes, independent of other risk factor including age, sex, waist circumference, family history of diabetes, fasting serum glucose and insulin levels, HbA1c , systolic blood pressure and other conventional lipid measurements [hazard ratio per 1sd; 1.14 (95%CI 1.11-1.18) and 1.13 (95%CI 1.10-1.16), respectively; both P<0.001]. Atherogenic dyslipidaemia was more strongly associated with the development of Type2 diabetes than conventional lipid measurements, and this effect was independent of other well-established risk factor for diabetes.

An Equation to Estimate the Concentration of Serum Apolipoprotein B

BackgroundSeveral large prospective studies have demonstrated that apolipoprotein B (apoB) has greater value in predicting cardiovascular risk than any other lipid measurements. Currently, however, serum apoB levels are not routinely measured, because of the additional cost. The aim of this study was to develop an equation to estimate apoB from conventional lipid measurements including total cholesterol, HDL cholesterol, and triglycerides.MethodsData from a total of 78,127 subjects (47,057 men and 31,070 women), aged 15 to 88 years (mean age 41.8 years) were reviewed to develop an apoB equation. Additional datasets from the same institution and the NHANES obtained in 2007–2008 were used for internal (n = 73,445) and external validation (n = 3,097), respectively.ResultsWe developed an apoB equation based on a linear regression model that contains total cholesterol, triglycerides, and HDL cholesterol as terms (model 1). To more precisely estimate the serum apoB level, we adjusted mode1 1 using a cutoff serum triglyceride value of 270 mg/dl (model 2). Model 2 showed more randomly distributed residuals in patients with diabetes, atherogenic dyslipidemia, and those taking lipid-lowering agents than model 1. The residuals in the development, internal validation, and external validation datasets were also randomly distributed around 0 with no clear trends.ConclusionThe new equation we developed to estimate serum apoB concentrations is accurate and can be used in diverse subgroups of patients including those with diabetes, atherogenic dyslipidemia, and those taking lipid-lowering agents.

Effect of a traditional Mediterranean diet on apolipoproteins B, A-I, and their ratio: A randomized, controlled trial

ObjectivesApolipoprotein (Apo)B, ApoA-I, and their ratio could predict coronary heart disease (CHD) risk more accurately than conventional lipid measurements. Our aim was to assess the effect of a traditional Mediterranean diet (TMD) on apolipoproteins. MethodsHigh-cardiovascular risk subjects (n=551, 308 women and 243 men), aged 55–80 years, were recruited into a large, multicenter, randomized, controlled, parallel-group, clinical trial (The PREDIMED Study) aimed at testing the efficacy of TMD on primary cardiovascular disease prevention. Participants assigned to a low-fat diet (control) (n=177), or TMDs (TMD+virgin olive oil (VOO), n=181 or TMD+nuts, n=193) received nutritional education and either free VOO (ad libitum) or nuts (dose: 30g/day). A 3-month evaluation was performed. ResultsBoth TMDs promoted beneficial changes on classical cardiovascular risk factors. ApoA-I increased, and ApoB and ApoB/ApoA-I ratio decreased after TMD+VOO, the changes promoting a lower cardiometabolic risk. Changes in TMD+VOO versus low-fat diet were −2.9mg/dL (95% CI, −5.6 to −0.08), 3.3mg/dL (95% CI, 0.84 to 5.8), and −0.03mg/dL (−0.05 to −0.01) for ApoB, ApoA-I, and ApoB/ApoA-I ratio, respectively. ConclusionsIndividuals at high-cardiovascular risk who improved their diet toward a TMD pattern rich in virgin olive oil, reduced their Apo B and ApoB/ApoA-I ratio and improved ApoA-I concentrations.

Characterization of systemic metabolic phenotypes associated with subclinical atherosclerosis

Detailed molecular phenotyping gives insight into disease mechanisms and can individualize medical practice for improved risk assessment and treatment. We show in an epidemiological study (n = 4309) that the multi-metabolic profiles obtained by serum NMR metabonomics inherently associate with the extent of atherosclerosis already in preclinical stages. Data-driven analysis of the spectral profiles of healthy, young adults revealed three distinct metabolic phenotypes associated with high carotid intima-media thickness (IMT), a surrogate marker of cardiovascular disease. The phenotypes were characterized by varying combinations of well-known metabolic disturbances like elevated VLDL and LDL and low HDL levels. Low IMT was also associated with distinct metabolic phenotypes with lipoprotein as well as other biochemical characteristics partly opposing those found for the high IMT phenotypes. Profiles of low-molecular-weight metabolites quantified from the experimentation were also characteristic for the metabolic phenotypes and substantiate developments toward the use of multi-metabolic risk phenotypes. The methodology can be taken as a direct extension for the routine analytics used for the risk assessment of atherosclerosis; quantification of metabolites will complement and might even replace conventional lipid measurements. Serum NMR metabonomics is therefore anticipated as a rational option for comprehensive cardiovascular risk assessment.

Lipoprotein Abnormalities Associated with Mild Impairment of Kidney Function in the Multi-Ethnic Study of Atherosclerosis

Impaired kidney function is associated with increased risk for cardiovascular disease and may progress over time to end-stage renal disease. Abnormal lipoprotein metabolism has been implicated as a possible cause of these complications, but lipoproteins have not been described at the earliest stages of kidney disease. This study examined cross-sectional associations of serum cystatin C with conventional lipid measurements and detailed nuclear magnetic resonance lipoprotein measurements in the community-based Multi-Ethnic Study of Atherosclerosis. A total of 5109 participants with estimated glomerular filtration rate > or =60 ml/min per 1.73 m(2) were included in analyses. Adjusting for age, gender, race/ethnicity, diabetes, impaired fasting glucose, BP, smoking, medications, body mass index, and albuminuria, greater cystatin C concentrations were associated with progressively unfavorable lipid and lipoprotein concentrations, including greater triglyceride concentration (+22 mg/dl, comparing fifth versus first quintiles of cystatin C) and lesser high-density lipoprotein cholesterol concentration (-7 mg/dl) but not with low-density lipoprotein cholesterol measured using conventional methods. When low-density lipoprotein particle subclasses were examined in more detail using nuclear magnetic resonance, greater cystatin C was associated with greater concentrations of atherogenic small low-density lipoprotein particles (+63 nmol/L) and intermediate-density lipoprotein particles (+6 nmol/L) and with a decrease in mean low-density lipoprotein particle size. Lipoprotein abnormalities are present with milder degrees of renal impairment than previously recognized, and abnormalities in low-density lipoprotein particle distribution may not be appreciated using conventional lipid measurements. These abnormalities may contribute to kidney disease progression and/or cardiovascular disease.

Antiretroviral therapy in HIV‐positive men is associated with increased apolipoprotein CIII in triglyceride‐rich lipoproteins

Dyslipidaemia has become a common problem in HIV disease, especially in patients on current antiretroviral therapy. However, the pathogenic mechanisms involved are not well understood or documented using conventional lipid measurements. Using a cross-sectional design, the prevalence of abnormal standard lipid measurements and novel biomarkers for abnormal lipid metabolism was determined in 271 HIV-positive men from two HIV clinics in Atlanta, GA, USA. A total of 147 men were treated with protease inhibitors (PIs) for >3 months (54%), 84 were treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) for >3 months (31%) and 40 had not received antiretroviral therapy in the past 3 months (15%). Patients being treated with a PI had higher total cholesterol and triglyceride (TG) levels than patients on no therapy (P<0.05 for each). Patients in the NNRTI group had higher TG, lower high-density lipoprotein (HDL) levels, and higher low-density lipoprotein (LDL) levels than patients on no therapy (P<0.05 for each). Patients treated with either PIs or NNRTIs were more likely to have higher apolipoprotein CIII (apoCIII) levels (P<0.05 for each) than patients on no therapy. Elevated TG was associated with disproportionably elevated apoCIII levels in both treatment groups. In this cross-sectional study of HIV-infected men, either PI or NNRTI therapy elevated levels of TG and apoCIII. Higher concentrations of apoCIII in apoB-containing lipoproteins [very low-density lipoproteins (VLDLs), intermediate density lipoprotein (IDL) and LDLs] have been predictive of an increased incidence of coronary events in clinical trials and more rapid progression of coronary lesions measured by angiography. These findings, on a background of an older population with additional risk factors of smoking and diabetes, portend future atherosclerotic events in these patients.

Diabetes and atherosclerosis: an epidemiologic view.

Diabetes is associated with changes in plasma lipids and lipoproteins into atherogenic direction. In IDDM these changes are small or absent if good metabolic control can be maintained. Diabetic nephropathy is, however, associated with the appearance of dyslipoproteinemia. In NIDDM plasma total and VLDL triglyceride levels are elevated, and HDL-cholesterol level is decreased, and this pattern of dyslipoproteinemia does not always respond to improved control of hyperglycemia. Abnormalities of lipoprotein metabolism, not reflected in conventional plasma lipid and lipoprotein level measurements, and glucosylation of lipoproteins and resulting alterations in lipoprotein catabolism may be of importance in the enhanced atherogenesis in diabetes. Both IDDM and NIDDM are associated with an increased frequency of hypertension, but the underlying mechanisms appear to be different. In IDDM hypertension is usually associated with the development of diabetic nephropathy and thus with a long duration of the disease. In NIDDM hypertension is often present already at the time of diagnosis, and also in IGT, the precursor stage of NIDDM, the prevalence of hypertension is already increased. Obesity explains only in part the high prevalence of hypertension in patients with NIDDM. Diabetes is known to be associated with multiple abnormalities in hemostatic factors and, although these abnormalities may contribute importantly to the increased risk of ASVD in diabetic patients, information about their real role is scanty and conflicting. The impact of general major risk factors for ASVD, elevated plasma cholesterol, elevated blood pressure, and smoking, on the risk of ASVD appears to be similar in diabetics and nondiabetics. Only a relatively small proportion of the excessive occurrence of ASVD in diabetics can, however, be explained by the effects of diabetes on the levels of general risk factors for ASVD. This proportion mediated through the effects of diabetes on risk factors is larger in female diabetics than in male diabetics. The major proportion of the excess of ASVD in diabetics remains, however, unexplained and must be due to effects of diabetes itself through mechanisms that are incompletely understood.