Combined Hyperlipidemia Research Articles

Prevalence and pattern of dyslipidemia in Nepalese individuals with type 2 diabetes

BackgroundAtherogenic dyslipidemia is an important modifiable risk factor for cardiovascular disease among patients of type 2 diabetes mellitus. Timely detection and characterization of this condition help clinicians estimate future risk of cardiovascular disease and take appropriate preventive measures. The aim of this study was to determine the prevalence, pattern and predictors of dyslipidemia in a cohort of Nepalese patients with type 2 diabetes.ResultsWe found mixed dyslipidemia as the most prevalent (88.1%) and isolated dyslipidemia (10.1%) as the least prevalent forms of dyslipidemia in our patients. The most prevalent form of single dyslipidemia was high LDL-C (73.8%) and combined dyslipidemia was high TG, high LDL-C and low HDL-C (44.7%). Prevalence of all single and mixed dyslipidemia was higher in patients with poor glycemic control and hypertension. The glycemic status of patients correlated with their fasting serum lipid profile. Dyslipidemia was associated mainly with male gender, poor glycemic control and hypertension.ConclusionsAtherogenic dyslipidemia is associated mainly with male gender, poor glycemic control and hypertension. It is highly prevalent in Nepalese patients with type 2 diabetes. Urgent lifestyle modification, sustained glycemic control and aggressive lipid lowering treatment plans are necessary to minimize the future risk of cardiovascular disease in this population.

Familial dysbetalipoproteinemia: an underdiagnosed lipid disorder.

To review pathophysiological, epidemiological and clinical aspects of familial dysbetalipoproteinemia; a model disease for remnant metabolism and remnant-associated cardiovascular risk. Familial dysbetalipoproteinemia is characterized by remnant accumulation caused by impaired remnant clearance, and premature cardiovascular disease. Most familial dysbetalipoproteinemia patients are homozygous for apolipoprotein ε2, which is associated with decreased binding of apolipoprotein E to the LDL receptor. Although familial dysbetalipoproteinemia is an autosomal recessive disease in most cases, 10% is caused by autosomal dominant mutations. Of people with an ε2ε2 genotype 15% develops familial dysbetalipoproteinemia, which is associated with secondary risk factors, such as obesity and insulin resistance, that inhibit remnant clearance by degradation of the heparan sulfate proteoglycan receptor. The prevalence of familial dysbetalipoproteinemia ranges from 0.12 to 0.40% depending on the definition used. Clinical characteristics of familial dysbetalipoproteinemia are xanthomas and mixed hyperlipidemia (high total cholesterol and triglycerides); the primary lipid treatment goal in familial dysbetalipoproteinemia is non-HDL-cholesterol; and treatment consists of dietary therapy and treatment with statin and fibrate combination. Familial dysbetalipoproteinemia is a relatively common, though often not diagnosed, lipid disorder characterized by mixed hyperlipidemia, remnant accumulation and premature cardiovascular disease, which should be treated with dietary therapy and statin and fibrate combination.

How to assess and manage cardiovascular risk associated with lipid alterations beyond LDL

Background and aimsThe maintenance of clinically recommended levels of low-density lipoprotein cholesterol (LDL-C) through a statin therapy is a gold standard in the management of patients with dyslipidaemia and cardiovascular disease (CVD). However, even when LDL-C levels are at or below clinically recommended target levels, residual cardiovascular (CV) risk still remains. Therefore, assessing lipoproteins beyond LDL-C in managing CV risk is imperative. MethodsA working group of clinical experts have assessed the role of lipoproteins other than LDL-C in identifying the CV risk in patients with dyslipidaemia and CVD and in the management of atherogenic dyslipidaemia associated with a number of other diseases. The recommendations, in line with the European guidelines, are presented. ResultsA thorough evaluation of clinical data by the expert working group resulted in recommendations to consider non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), remnant cholesterol and lipoprotein(a) (Lp[a]) as biomarkers of residual CV risk in patients with CVD. Elevated Lp(a) levels were also suggested to be a causal factor. The experts highlighted the significance of non-HDL-C and triglycerides (TG) in atherogenic dyslipidaemia associated with type 2 diabetes, metabolic syndrome, chronic kidney disease (CKD) and familial combined hyperlipidaemia (FCH). The working group recommended combinatorial therapeutic approaches in high-risk patients, including agents impacting on TG and HDL-C levels. ConclusionsEvaluation of a lipoprotein landscape when LDL-C levels remain low strongly supports the role of non-HDL-C, Lp(a) and TGs in identifying patients with increased residual risk of CV and in selecting their treatment strategy.

Does lifestyle contribute to disease severity in patients with inherited lipid disorders?

Patients with familial hypercholesterolemia, familial combined hyperlipidemia and hyperlipoprotein(a) are at high cardiovascular risk. Increasing evidence suggest that lifestyle-related risk factors such as physical inactivity, and poor diet quality could influence cardiovascular risk in these patients. Our objective is to review the evidence that supports the role of lifestyle-related factors in the prediction of cardiovascular risk in patients with inherited lipid disorders. Recent studies have shown that smoking, a poor diet quality, physical inactivity, fitness levels, abdominal obesity, insulin resistance, and type 2 diabetes were associated with the presence of atherosclerosis and long-term cardiovascular outcomes in patients with familial hypercholesterolemia. Recent evidence also suggest that managing other cardiovascular risk factors such as cholesterol levels, obesity, glycemic control, blood pressure, smoking, physical inactivity, and diet quality could reduce long-term cardiovascular risk associated with hyperlipoprotein(a). Whether targeting these risk factors could ultimately decrease cardiovascular risk in these patients remains unknown. Although reducing the number of atherogenic apolipoprotein-B containing particle with lipid-lowering therapy represents the cornerstone of treatment of patients with inherited lipid disorders, lifestyle-related risk factors such as physical inactivity and poor diet quality need to be targeted for the optimal management of these high-risk patients.

Association Between the Presence of Carotid Artery Plaque and Cardiovascular Events in Patients With Genetic Hypercholesterolemia

Introduction and objectivesThe equations used in the general population to calculate cardiovascular risk are not useful in genetic hypercholesterolemia (GH). Carotid plaque detection has proved useful in cardiovascular prediction and risk reclassification but there have been no studies of its usefulness in GH. The aim of this study was to determine the association between the presence of carotid artery plaque and the occurrence of cardiovascular events in patients with GH. MethodsThis study included 1778 persons with GH. The mean follow-up until the occurrence of cardiovascular events was 6.26 years. At presentation, the presence of carotid artery plaque was studied by high-resolution ultrasound. ResultsCarotid artery plaque was found in 661 (37.2%) patients: 31.9% with familial hypercholesterolemia, 39.8% with familial combined hyperlipidemia, 45.5% with dysbetalipoproteinemia, and 43.2% with polygenic hypercholesterolemia. During follow-up, 58 patients had a cardiovascular event. Event rates were 6354/100 000 (95%CI, 4432.4-8275.6) in the group with plaque and 1432/100 000 (95%CI, 730.6-2134.3) in the group without plaque, with significant differences between the 2 groups (P < .001). The relative risk of an event was 4.34 (95CI%, 2.44-7.71; P < .001) times higher in patients with plaque and was 2.40 (95%CI, 1.27-4.56; P = .007) times higher after adjustment for major risk factors. The number of carotid artery plaques was positively associated with the risk of cardiovascular events. ConclusionsMost cardiovascular events occur in a subgroup of patients who can be identified by carotid plaque detection. These results support the use of plaque screening in this population and should help in risk stratification and treatment in GH.

Pitavastatin: A Review in Hypercholesterolemia.

Oral pitavastatin (Livalo®; Livazo®) is a competitive HMG-CoA reductase inhibitor that is available in the EU for the reduction of elevated total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels in adults with primary hypercholesterolemia and combined (mixed) dyslipidemia. In short-term, phase III or IV studies in this patient population, pitavastatin 1-4mg once daily was generally no less effective than presumed equipotent dosages of atorvastatin and simvastatin (including in patients with type 2 diabetes or≥2 cardiovascular risk factors) and was superior to pravastatin (including in patients aged≥65years) in lowering LDL-C levels. Pitavastatin provided sustained LDL-C-lowering efficacy over up to 60weeks' therapy in extension studies, and was associated with short- and longer-term improvements in several other lipid parameters. Short- and longer-term outcomes in studies in Asian patients were consistent with these findings. Pitavastatin was generally well tolerated and did not appear to adversely affect glucose metabolism parameters (e.g. fasting blood glucose, fasting plasma glucose, fasting plasma insulin, glycated hemoglobin) in short- and longer-term prospective and post-marketing surveillance studies in adults. Moreover, in combination with lifestyle modification advice, it was associated with a significant reduction in the risk of progression from impaired glucose tolerance to diabetes relative to lifestyle modification advice alone in a longer-term study in Japanese subjects. Thus, pitavastatin is an effective treatment option in adults with primary hypercholesterolemia and combined (mixed) dyslipidemia, including those at risk of developing type 2 diabetes.

The efficacy and safety of pitavastatin

In short-term, phase III or IV studies in Asian and European patients, pitavastatin 1, 2 and 4 mg once daily reduced LDL-Cholesterol (LDL-C) 34%, 42% and 47%, respectively. Pitavastatin provided sustained LDL-C-lowering efficacy over up to 60 weeks' therapy in extension studies. In comparative studies pitavastatin 4 mg and simvastatin 40 mg reduced LDL-C similarly, reduction in triglycerides and increase in HDL-Cholesterol (HDL-C) was more prominent with pitavastatin. In comparative studies with atorvastatin, pitavastatin 4mg was found to be more effective than 20 mg of atorvastatin, and a little less effective than 40 mg of atorvastatin. The increase in HDL-C demonstrated in short term studies sustained in long term, whereas with atorvastatin the increase in HDL-C was less prominent. Pitavastatin was generally well tolerated in these studies and most treatment emergent adverse events were mild or moderate and their frequency was not different from other statins. Pitavastatin did not appear to adversely affect glucose metabolism parameters (e.g. fasting blood glucose, fasting plasma insulin, glycated hemoglobin) in short- and longer-term prospective and post-marketing surveillance studies in adults. In conclusion, pitavastatin is an effective treatment option in adults with primary hypercholesterolemia and combined (mixed) dyslipidemia, including those at risk of developing type 2 diabetes.

High frequency of dyslipidemia in children and adolescents with Down Syndrome

To describe the frequency of dyslipidemia in a population of Chilean children and adolescents with DS. Retrospective study, including patients with DS, aged 2 to 18 years, who participated in a special health care program for people with DS in Health Net UC CHRISTUS, between 2007 and 2015. Patients who had a lipid profile between their routine laboratory tests were included. Clinical characteristics, relevant comorbidities, malformations, medications, nutritional status and pubertal development were obtained from medical records. Diagnosis of dyslipidemia was considered according to the criteria of the NHLBI 2011. The medical records of 218 children with DS were revised, 58,3% had some type of dyslipidemia. The most frequent single dyslipidemias were low HDL Chol (15,1%) and hypertriglyceridemia (12,8%). Atherogenic dyslipidemia (low HDL plus hypertriglyceridemia) was the most frequent combined dyslipidemia (13,3%). The occurrence of atherogenic dyslipidemia was not associated with overnutrition and obesity. A high frequency of dyslipidemia was found in Chilean children and adolescents with DS. Our results make us suggest that lipid profile should be performed early in all patients with DS, independent of the presence of risk factors for dyslipidemia.

Can Shear -Wave Elastography be used to detect liver decreased stiffness in liver due to hepatic steatosis?

The most common liver disorder in developed countries is the Non-alcoholic fatty liver disease (NAFLD) [1,2]. Insulin resistance and the metabolic syndrome are both related to NAFLD [3]. The disease occurs up to 80% of obese people [4]. The most extreme form of NAFLD is Nonalcoholic steatohepatitis (NASH) which is the major cause of cirrhosis of the liver of unknown cause [5]. More commonly NAFLD is detected routine blood tests followed by diagnosed abnormal liver function tests. In the presence of insulin resistance and metabolic syndrome (obesity, combined hyperlipidemia, diabetes mellitus (type II), and high blood pressure ) NAFLD may seen often [3,5]. A spectrum of disease activity is being considered to cover in NAFLD. This spectrum begins as fatty accumulation in the liver (hepatic steatosis). A liver can remain fatty liver could work without any disturbing liver function, but by varying mechanisms and possible insults to the liver may also progress to become non-alcoholic steatohepatitis (NASH), a state in which steatosis is combined with inflammation and fibrosis (steatohepatitis). NASH is a progressive disease: over a 10-year period and also up to 20% of patients with NASH may develop cirrhosis of the liver, and 10% will suffer death related to liver disease [6].

Asociación de la presencia de placa carotídea en la aparición de eventos cardiovasculares en pacientes con hipercolesterolemias genéticas

Introduction and objectivesThe equations used in the general population to calculate cardiovascular risk are not useful in genetic hypercholesterolemia (GH). Carotid plaque detection has proved useful in cardiovascular prediction and risk reclassification but there have been no studies of its usefulness in GH. The aim of this study was to determine the association between the presence of carotid artery plaque and the occurrence of cardiovascular events in patients with GH. MethodsThis study included 1778 persons with GH. The mean follow-up until the occurrence of cardiovascular events was 6.26 years. At presentation, the presence of carotid artery plaque was studied by high-resolution ultrasound. ResultsCarotid artery plaque was found in 661 (37.2%) patients: 31.9% with familial hypercholesterolemia, 39.8% with familial combined hyperlipidemia, 45.5% with dysbetalipoproteinemia, and 43.2% with polygenic hypercholesterolemia. During follow-up, 58 patients had a cardiovascular event. Event rates were 6354/100 000 (95%CI, 4432.4-8275.6) in the group with plaque and 1432/100 000 (95%CI, 730.6-2134.3) in the group without plaque, with significant differences between the 2 groups (P < .001). The relative risk of an event was 4.34 (95CI%, 2.44-7.71; P < .001) times higher in patients with plaque and was 2.40 (95%CI, 1.27-4.56; P = .007) times higher after adjustment for major risk factors. The number of carotid artery plaques was positively associated with the risk of cardiovascular events. ConclusionsMost cardiovascular events occur in a subgroup of patients who can be identified by carotid plaque detection. These results support the use of plaque screening in this population and should help in risk stratification and treatment in GH.Full English text available from:www.revespcardiol.org/en

Serum non-HDL cholesterol to apolipoprotein B ratio as a screening test for familial dysbetalipoproteinaemia (Type III hyperlipidaemia) in patients with mixed hyperlipidaemia

Serum non-HDL cholesterol to apolipoprotein B ratio as a screening test for familial dysbetalipoproteinaemia (Type III hyperlipidaemia) in patients with mixed hyperlipidaemia

Abstract 12896: ApoC3-Gln38Lys Variant is a Gain-of-function Mutation Associated With Human Hypertriglyceridemia

Introduction: Cell culture and animal studies have suggested that expression of human apoC3 in liver cells can exert an intracellular role in promoting production of triglyceride (TG)-rich VLDL (VLDL1) under lipid-rich conditions. Previously, hypotriglyceridemia in human subjects have been linked to several loss-of-function apoC3 mutations, namely Ala23Thr and Lys58Glu. Conversely, hypertriglyceridemia has also been linked to an apoC3 variant. For example, the Gln38Lys variant was originally identified in human subjects of Mexican origin; heterozugous carriers of Gln38Lys exhibited moderate hypertriglyceridemia. Hypothesis: We hypothesized that the Gln38Lys variant is a gain-of-function mutation that promotes hepatic VLDL assembly/secretion. Methods: The recombinant Gln38Lys variant was either expressed in McA-RH7777 cells devoid of endogenous apoC3, or else expressed in apoc3-null mice using adenovirus-mediated gene transfer. The effect of Gln38Lys expression on hepatic lipogenesis, VLDL1 production, and glucose homeostasis was contrasted with that of wildtype apoC3. Results: Gln38Lys expression in McA-RH7777 cells and apoc3-null mice resulted in increased VLDL1-TG secretion, which was accompanied with increased de novo lipogenesis, increased adipogenesis, and severe hepatic steatosis (i.e. accumulation of TG and cholesteryl esters). Gln38Lys expression also increased glucose uptake and hepatic glycogen content, suggesting that apoC3 may play a role in hepatic glucose homeostasis. Live cell imaging revealed prominent association of apoC3 with endosomes, and the Gln38Lys-associated endosomes exhibited robust trafficking between Golgi apparatus and the cell periphery. Next generation sequencing of 1557 DNA samples from patients (of European, Chinese, African, and South Asian origins) with dyslipidemia (including hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia) did not detect Gln38Lys variant, nor was the Gln38Lys variant found in the ExAC databases containing 60,706 individuals. Conclusions: Gln38Lys is a rare, gain-of-function variant that may stimulate TG-rich VLDL1 production under lipid-rich conditions, contributing to hypertriglyceridemia..

ASGR1 - a new target for lowering non-HDL cholesterol.

Non-HDL cholesterol (non-HDL-C) has been introduced as an alternative cardiovascular (CV) risk marker and a secondary therapeutic target in patients with combined hyperlipidemia, diabetes mellitus, metabolic syndrome, or chronic kidney disease. An important genetic study on the Icelandic population has recently identified a strong link between a new gene – ASGR1 (for asialoglycoprotein receptor) – mutation, plasma non-HDL-C levels, and coronary heart disease (CHD). Heterozygous carriers of a rare noncoding 12-base-pair (bp) deletion (del12 deletion) in intron 4 of ASGR1 had a 13.6 mg/dl lower level of non-HDL-C and a 34% lower risk of CHD than non carriers. The cardioprotective effect of ASGR1 loss-of-function is surprisingly larger than predicted by its effect on the levels of non-HDL-C, which suggests that the atheroprotective effects of del12 mutation go beyond the lowering of serum cholesterol levels. This has shed some light on a new path – the sialylation pathway – possibly leading to a novel therapy that neutralize ASGR1 for heart disease prevention and treatment.

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C.

Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 g/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit.

Butter Blood

Acute pancreatitis induced by hypertriglyceridemia is a rare but well-established complication, though the exact pathogenesis remains unclear. Estimated rates account for 1-4% of acute pancreatitis cases with noticeable rising risk as serum levels increase (triglycerides > 1000 carry 5% risk; triglycerides > 2000 carry 10-20% risk). Occurrence is more commonly associated in those with acquired disorders (such as diabetes mellitus, hypothyroidism, obesity, pregnancy, medication-induced, nephrotic syndrome) than in those with inborn errors of lipoprotein metabolism (such as familial combined hyperlipidemia, familial hypertriglyceridemia). Therapeutic measures in such patients include standard pancreatitis management, along with lipidlowering oral agents, low-molecular weight heparin, and insulin in those who are diabetic. In situations where these measures fail to improve patient clinic course, plasma exchange is used to expedite removal of triglycerides (TG). Here, we present a case of a noncompliant, insulin-dependent diabetic patient found to have hypertriglyceridemia-induced pancreatitis. Case: A 40-year-old African American male with poorly-controlled, insulin-dependent diabetes presented to our facility with complaints of abdominal pain accompanied with nausea and vomiting. Laboratory examination was consistent with severe pancreatitis and mild ketoacidosis (Table 1). Abdominal CT scan confirmed the clinical diagnosis of severe pancreatitis of the pancreatic head and uncinate process with inflammation of the adjacent duodenum (Image 1-2). The appearance of latescent serum accompanied with lipemic serum pointed toward a diagnosis of pancreatitis secondary to hypertriglyceridemia.Figure 1Figure 2Figure 3As our patient did not carry a familial history of genetic abnormalities of lipoprotein metabolism, we attributed the hypertriglyceridemia secondary to his poorly-controlled diabetes and diabetic ketoacidosis. The patient was treated with gemfibrozil, atorvastatin, IV fluids, bowel rest, and insulin infusion. Improvement of his triglyceride level coincided with improvement in blood sugars and abdominal pain. Plasmapharesis was not undertaken in this patient given improvement with conventional therapies.

Endothelial progenitor cells before and after treatment with metformin in patients with familial combined hyperlipidemia and insulin resistance

Objectives: Familial combined hyperlipidemia (FCHL) is a disorder of metabolism, associated to increased cardiovascular (CV) risk, characterized by the overproduction of very low-density lipoprotein, by the altered remnants catabolism, and by an high prevalence of insulin resistance (IR). Endothelial progenitor cells (EPCs) are a heterogeneous population of cells with the ability to differentiate into cell types of different organs and systems. CD34+EPCs have already been evaluated in different clinical conditions, finding associations between the severity of disease and cell count. IR was acknowledged as a strong prevalence predictor of CV disease. Several authors have suggested that metformin may increase EPC levels in diabetic patients, but to date there are no studies about CD34+EPCs in non-diabetic-IR patients.

Familial combined hyperlipidemia in children: Biochemical characterization in pediatric age

Familial combined hyperlipidemia in children: Biochemical characterization in pediatric age

A ubiquitous transcription factor influences diet-induced thermogenesis and sensitizes BAT to noradrenergic stimuli improving cardiometabolic health

Objectives: USF1 is a transcription factor associated with familial combined hyperlipidemia and CAD in humans. We have previously shown that Usf1-deficient mice are protected against obesity and dyslipidemia.

Efficacy and safety of long-term coadministration of fenofibrate and ezetimibe in patients with combined hyperlipidemia: Results of the efectl trial

Efficacy and safety of long-term coadministration of fenofibrate and ezetimibe in patients with combined hyperlipidemia: Results of the efectl trial

Familial combined hyperlipidemia and hyperlipoprotein(a) as phenotypic mimics of familial hypercholesterolemia: Frequencies, associations and predictions

A significant proportion of index cases presenting with phenotypic familial hypercholesterolemia (FH) are not found to have a pathogenic mutation and may have other inherited conditions. Familial combined hyperlipidemia (FCHL) and elevated lipoprotein(a) [Lp(a)] may mimic FH, but the frequency and correlates of these disorders among mutation-negative FH patients have yet to be established. The frequency of FCHL and elevated Lp(a) was investigated in 206 FH mutation-negative index cases attending a specialist lipid clinic. An FCHL diagnostic nomogram was applied to each index case; a positive diagnosis was made in patients with a probability score exceeding 90%. Plasma Lp(a) concentration was measured by immunoassay, with an elevated level defined as ≥0.5g/L. Clinical characteristics, including coronary artery disease (CAD) events, were compared between those with and without FCHL and hyper-Lp(a). Of mutation-negative FH patients, 51.9% had probable FCHL. These patients were older (P=.002), had a higher BMI (P=.019) and systolic (P=.001) and diastolic blood pressures (P=.001) compared with those without FCHL. Elevated Lp(a) was observed in 44.7% of cases, and there were no significant differences in clinical characteristics with Lp(a) status. The presence of elevated Lp(a) (P=.002), but not FCHL, predicted CAD events. This association was independent of established CAD risk factors (P=.032). FCHL and elevated Lp(a) are common disorders in patients with mutation-negative FH. Among such patients, FCHL co-expresses with components of the metabolic syndrome, and elevated Lp(a) is the major contributor to increased CAD risk.