Krishnaji Kulkarni

Background: Plasma triglyceride levels correspond to the sum of the triglyceride (TG) content in triglyceride-rich lipoproteins (TRL) and their remnants. Experimental studies have shown TRL adverse effects in the brain, but there is limited data about their role in cognitive function. We investigated the cross-sectional association of TG and TRL-ch...

Importance Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or greater, laboratories reflexively perform direct LDL-C (dLDL-C) measurement. The use of direct chemical LDL-C assays and estimation of LDL-C via the National Institutes of Hea...

Purpose/aims: The relationship between thyroid-stimulating hormone (TSH) and lipoprotein subfractions by Vertical Auto Profile (VAP) is unclear. We aimed to evaluate lipoprotein profiles according to TSH levels in euthyroid individuals.Material and Methods: Cross-sectional analysis of 3,525 participants from the Brazilian Longitudinal Study of Adu...

Background Remnant lipoprotein cholesterol (RLP-C) is a risk factor for atherosclerotic cardiovascular disease, but there is no standard method for measurement. Some studies have used very low-density lipoprotein cholesterol (VLDL-C) estimated by the Friedewald equation to approximate RLP-C using a basic lipid panel, while others have attempted to...

Background: Although HDL-C is known to be inversely associated with cardiovascular risk, no causal relationship has been demonstrated. Since HDL-C comprises a group of different subfractions, they might have different effects on atherosclerosis, and its effects may be modified by the presence of diabetes mellitus. Background: Although High-Density...

Background and purpose: Although the relation between thyroid disorders and heart diseases had been described since decades ago, the association of thyroid-stimulating hormone (TSH) and lipoproteins is not very well elucidated. Hypothesis: to verify if there are associations with TSH levels, lipid and lipoprotein subfractions in the Brazilian Longi...

Introduction: Deficient 25-hydroxyvitamin D [25(OH)D] levels have been associated with dyslipidemia and cardiovascular diseases, though the underlying mechanism of these associations is uncertain. We analyzed associations between vitamin D and other non-lipid biomarkers of cardiovascular risk to better elucidate possible relationships between defic...

Introduction: Remnant lipoproteins (RLP) are triglyceride-rich cholesterol-containing particles and an emerging risk factor for development of cardiovascular disease, but there is no standard method for RLP measurement. Some studies have used very low-density lipoprotein cholesterol (VLDL-C) calculated by the Friedewald equation to estimate RLP cho...

Background Remnant lipoproteins (RLPs), the triglyceride‐enriched precursors to low‐density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP‐C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts. Methods and ResultsWe anal...

Background: Apolipoprotein B (apoB) levels in plasma are proportional to the number of all atherogenic, non-high-density lipoprotein (HDL) particles. Non-HDL-C concentration - the aggregate cholesterol carried by apoB-containing particles - is usually highly correlated with apoB levels. This study aimed to describe individuals with discordance betw...

Appendix S1. Lipoprotein Investigators Collaborative (LIC) Study Group Table S1. Framingham Offspring Cohort Study Table S2. Jackson Heart Study Figure S1. Splines demonstrating approximately linear association between remnant lipoprotein cholesterol (RLP‐C) and coronary heart disease (CHD) risk in the Jackson Heart and Framingham Offspring Coho...

Background: Low 25-hydroxyvitamin D [25(OH)D] is associated with an increased risk of cardiovascular disease. The mechanism of this observation is unknown but may be explained by other non-lipid markers of cardiovascular risk.

Background and aims: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear. While reducing serum total homocysteine (tHcy) has been shown to decrease strokes, there is no evidence for an effect on myocardial infarctions in randomized controlled trials. This study aims to exam...

Background: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear. Complicating this association, reducing serum homocysteine (Hcy) has not been shown to decrease cardiovascular disease events in randomized controlled trials. This study aims to examine the relationship between...

Background The effect of alirocumab on potentially atherogenic lipoprotein subfractions was assessed in a post hoc analysis using the vertical auto profile (VAP) method. Methods Patients from three Phase II studies with low-density lipoprotein cholesterol (LDL-C) ≥2.59 mmol/L (100 mg/dL) at baseline on stable statin therapy were randomised to recei...

Background: Dyslipidemia plays a significant role in the progression of cardiovascular disease. The apolipoprotein (apo) A1 remnant ratio (apo A1/VLDL3-C + IDL-C) has recently been shown to be a strong predictor of death/myocardial infarction risk among women >50 years undergoing angiography. However, whether this ratio is associated with coronary...

Background: Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that, like other apolipoprotein B-containing lipoproteins, are atherogenic. Prior observational studies suggest paradoxically better outcomes in hypercholesterolemic patients who sustain an acute myocardial infarction (AMI), one of several known recurrent risk paradoxes....

Background: Cross-sectional studies have found an association between deficiencies in serum vitamin D, as measured by 25-hydroxyvitamin D (25[OH]D), and an atherogenic lipid profile. These studies have focused on a limited panel of lipid values including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and...

Background: High levels of the triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio are associated with obesity, metabolic syndrome, and insulin resistance. Objectives: We evaluated variability in the remaining lipid profile, especially remnant lipoprotein particle cholesterol (RLP-C) and its components (very low-density lipoprot...

Background—The total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, estimated low-density lipoprotein cholesterol (LDL-C), and non-HDL-C are routinely available from the standard lipid profile. We aimed to assess the extent of patient-level discordance of TC/HDL-C with LDL-C and non-HDL-C because discordance suggests the poss...

Aims: We aimed to clarify the associations of high-density lipoprotein cholesterol (HDL-C) subclasses with incident coronary heart disease (CHD) in two large primary prevention cohorts. Methods: We measured cholesterol at baseline from the two major HDL subfractions (larger, more buoyant HDL2 and smaller, denser HDL3) separated by density gradie...

The present disclosure provides methods to predict the risk of CHD and/or clinical manifestations of CHD in a subject. In one embodiment, the method involves measuring the levels or concentration of apo A1, a subclass of HDL, HDL3, or a combination of the foregoing. The methods of the present disclosure are particularly useful when the subject has...

Aims: High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention. Methods and results: We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH st...

Blood lipids have major cardiovascular and public health implications. Lipid-lowering drugs are prescribed based in part on categorization of patients into normal or abnormal lipid metabolism, yet relatively little emphasis has been placed on: (1) the accuracy of current lipid measures used in clinical practice, (2) the reliability of current categ...

To examine patient-level discordance between population percentiles of non-HDL cholesterol (non-HDL-C) and LDL cholesterol (LDL-C). Non-HDL-C is an alternative to LDL-C for risk stratification and lipid-lowering therapy. The justification for the present guideline-based non-HDL-C cutpoints of 30 mg/dL higher than LDL-C cutpoints remains largely unt...

Background: Dense LDL phenotypes are associated with increased atherogenicity, and are commonly evaluated for the purposes of atherosclerosis research and cardiovascular risk discrimination. Objective: To examine the ability of LDL subclasses, expressed as a ratio of dense-to-buoyant subclass, to predict LDL density phenotype. Methods: LDL subclass...

Background Women often lag behind men in their risk of cardiovascular events. However, with age and the onset of menopause, women’s cardiovascular risk eventually becomes similar to that of men. This change in risk may, in part, be attributable to a shift to a more atherogenic lipid profile. Our objective was to evaluate standard- and sub-lipid par...

Objectives: The aim of this study was to compare Friedewald-estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values. Background: LDL-C is routinely estimated by the Friedewald equation to guide treatment; however, compatibility with direct measurement has received relatively little scrutiny, especially at levels <70 mg...

Background: The TC/HDL-C ratio, Non-HDL-C, and LDL-C are each routinely available in clinical practice. Considerable patient-level discordance between these markers would suggest the possibility of complementary information.

Background: Low density lipoprotein cholesterol (LDL-C) has long been the cornerstone of lipid lowering therapy for atherosclerosis risk reduction. However, recent investigations have reported the importance of subfractions and other atherogenic lipoproteins in reducing risk. We evaluated the predictive ability of atherogenic lipoproteins and subfr...

There is little known about the relative predictive value of different lipoprotein(a) [Lp(a)] assays in clinical use, although each has been shown to predict similar incremental risk over conventional clinical and lipid risk factors. Thus, we examined the classification behavior of two commonly used Lp(a) assays and their associations with other li...

Epidemiologic studies suggest that LDL particle concentration (LDL-P) may remain elevated at guideline recommended LDL cholesterol goals, representing a source of residual risk. We examined the following seven separate lipid parameters in achieving the LDL-P goal of <1000 nmol/L goal for very high risk secondary prevention: total cholesterol to HDL...

Lipoprotein(a) [Lp(a)] is a complex lipoprotein consisting of a low-density lipoprotein (LDL)-like ApoB₁₀₀-containing core particle covalently bound to apo(a), a large functionally complex glycoprotein. The mechanisms of Lp(a) metabolism and its interactions with cell-surface lipoprotein receptors are incompletely understood. In this study, we inve...

Progression of carotid intima-media thickness (CIMT) is a surrogate indicator for the early stages of atherosclerosis. The study investigated relationships between baseline lipoprotein cholesterol, triglyceride (TG), and apolipoprotein (Apo) B levels assessed with density gradient ultracentrifugation (DGU) and progression of posterior wall common C...

Background: Recent evidence suggests that LDL levels alone may be an incomplete assessment of cardiovascular risk, given the emerging importance of LDL density. Specifically, an excess of low-density LDL (Pattern B vs. A/B or A) has been shown in primary prevention cohorts to be particularly atherogenic. To date, however, the prevalence of Pattern...

The purpose of this study was to determine whether an association exists between adiponectin and plaque composition in human coronary arteries. Adiponectin is an adipocyte-derived protein with antiatherogenic and insulin-sensitizing properties. To date, the relationship between adiponectin and plaque composition is unknown. Fasting blood samples we...

Vertical auto profile (VAP) method is a direct single test for measuring comprehensive lipoprotein cholesterol profile. It is based on a well-established method of ultracentrifugation that uses vertical rotor and single density gradient spin. VAP provides cholesterol concentrations of total lipoprotein, high-density lipoprotein (HDL), low-density l...

To test the hypothesis that a dietary omega-3 fatty acid, docosahexaenoic acid, improves the lipoprotein subclass profile of children who have hyperlipidemia, we conducted a randomized, double-blind, placebo-controlled study. Children who had hyperlipidemia (n = 20) were stabilized on a low-fat diet for 6 weeks and then randomized to receive 1.2 g/...

The relationship between insulin resistance, dyslipidemia, HIV infection, and antiretroviral therapy remains unclear, and the atherogenic nature of lipid and lipoprotein profiles in HIV-infected patients has not been fully characterized. We measured plasma lipid and lipoprotein subfractions using Vertical Auto Profile-II methodology and directly me...

The lipoprotein abnormalities first associated with insulin resistance (IR) and compensatory hyperinsulinemia were high plasma triglyceride (TG) and low HDL-cholesterol (HDL-C) concentrations (1)(2). It is now known that the characteristic IR-associated dyslipidemia also includes a shift to smaller, denser LDL particles (pattern B), enhanced postpr...

Increased physical activity is related to reduced risk of cardiovascular disease, possibly because it leads to improvement in the lipoprotein profile. However, the amount of exercise training required for optimal benefit is unknown. In a prospective, randomized study, we investigated the effects of the amount and intensity of exercise on lipoprotei...

Questions remain concerning the effect of variations in cholesterol intake on plasma cholesterol concentration, as well as on the role of factors modulating the metabolic impact of this dietary intervention. To define the impact of wide variations in dietary cholesterol intake on plasma total and low-density lipoprotein (LDL) cholesterol concentrat...

A simple and convenient method to determine plasma cholesterol profiles in individual mouse plasma samples is not presently available. With commonly used methods, plasma samples from several animals in a study group must often be pooled and analyzed, usually by the fast phase liquid chromatography (FPLC) method. The Column Lipoprotein Profile (or C...

There is increasing evidence to believe that Asian Indians are at an increased risk of coronary heart disease (CHD), which cannot be attributed to the common risk factors. Individuals with small, dense LDL phenotype are also known to be at increased risk of CHD. Our objective was to examine whether the prevalence of smaller and denser LDL particles...

To determine whether Asian Indians (Indians), a group known to have high rates of coronary heart disease, have increased platelet activation and fibrinogen levels relative to white Americans of European origin (whites). Forty healthy, non-smoking Indians, aged 25-45, were matched with 40 healthy whites for age (within 3 years) and gender. Platelet...

Of the several existing methods for quantification of major subspecies of high density lipoprotein (HDL), HDL2 and HDL3, the methods based upon double precipitation are particularly useful for large-scale studies or for routine assay because of their high speed and low cost. The Vertical Auto Profile-II (VAP-II) method developed in our laboratory p...

Low density lipoprotein (LDL) particles are heterogeneous in size, density, and chemical composition; small, dense LDL may be more atherogenic than large, buoyant LDL. We have developed a rapid microscale method called LDL VAP-II (Vertical Auto Profile-II) for quantification of cholesterol in LDL subclasses. The method is based upon a short (1 h) s...

We have developed a high resolution microvolume Vertical Auto Profile (VAP) method for the simultaneous measurement of cholesterol in all lipoprotein classes, including lipoprotein[a] (Lp[a]) and intermediate density lipoprotein (IDL). This method, designated as VAP-II, uses a non-segmented continuous flow (controlled-dispersion flow) analyzer for...

This new, highly sensitive analytical system, based on controlled dispersion of the flowing sample, gives a rapid, continuous, and direct analysis for cholesterol in all lipoprotein classes, separated by single vertical-spin density-gradient ultracentrifugation. In this Vertical Auto Profile-II fingerstick system, designated VAP-IIfs, a narrow-bore...

Electrodes au platine modifie par adsorption d'iode et recouvert d'acetate de cellulose, ou au carbone vitreux modifie par anodisation dans un melange de RuCl 3 /K 4 Ru(N) 6 . Application au dosage de thiocyanates dans les urines, avec elimination des interferences causees par l'acide urique et l'acide ascorbique par electrolyse a potentiel control...

A glassy-carbon electrode modified with a ruthenium-containing inorganic film was used for the flow-injection determination of As(III). The linear working range was 5-100 muM, and the detection limit was 300 pg. The response was reproducible for periods of several days. A glassy-carbon electrode modified by adsorption of a quaternized poly(4-vinylp...

The modification of a glassy carbon electrode by coating it with poly(4-vinylpyridine), which is subsequently impregnated with IrCl64–,3–, yields an indicator electrode that permits the detection of 0.07 p.p.m. (mg l–1) of nitrite in 20 µl of solution in a flow injection experiment. The slope of the calibration graph in the range 1 × 10–5-1 × 10–3M...

This new, highlysensitiveanalytical system,based on controlled dispersion ofthe flowingsample,givesa rapid, continuous, and directanalysisfor cholesterolin all lipo- proteinclasses,separated by singlevertical-spin density- gradientultracentrifugation. In this VerticalAutoProfile-Il tingersticksystem,designatedVAP-Ilfs, a narrow-bore Tefloncoil serv...