Plasma triglycerides related decrease in high-density lipoprotein cholesterol and its association with myocardial infarction in heterozygous familial hypercholesterolemia

doi:10.1016/0026-0495(86)90146-0

Metabolism

Volume 35, Issue 4, April 1986, Pages 311-316

https://doi.org/10.1016/0026-0495(86)90146-0 Get rights and content

Abstract

Recent studies suggest that decreased levels of high-density liopoprotein (HDL) may contribute to the risk of premature occlusive atherosclerosis in familial hypercholesterolemia (FH). To investigate further, we have analyzed the concentration as well as distribution of HDL cholesterol in relation to plasma triglycerides and their influence on ischaemic heart disease in FH subjects. The study was carried out in 71 men with heterozygous FH and 46 matched controls. FH subjects were relatively young with a mean age of 38 ± 11 years. Tendon xanthomatas were observed in 57% of the subjects, whereas ischemic heart disease was identified in 33%. Compared to normals, the mean value of HDL cholesterol is significantly reduced by 21% in FH heterozygotes (42 ± 12 v 33 ± 9 mg/dL, P < 0.001). The decrease in HDL cholesterol is highly correlated to the levels of plasma triglycerides (r = −0.50, P < 0.001) and VLDL cholesterol (r = −0.53, P < 0.001). Moreover, HDL cholesterol decrease is not associated with elevated levels of LDL cholesterol (r = −0.20, NS), which is the primary characteristic feature of FH subjects. However, HDL cholesterol decrease is weakly related to total plasma cholesterol concentration (r = −0.24, P < 0.05). The body weight is also contributory to the reduction of HDL cholesterol (r = −0.42, P < 0.01), probably due to its strong positive correlation to plasma triglycerides (r = +0.54, P < 0.001). Grouping of subjects on the basis of triglyceride levels of less than 200 mg/dL (IIa phenotype) and more than 200 mg/dL (IIb phenotype) shows that the concentration of HDL cholesterol undergoes a further significant decrease in the latter group (36 ± 9 v 30 ± 11 mg/dL, P < 0.001). Since the level of LDL cholesterol is similar in both groups (314 ± 68 v 316 ± 76 mg/dL, NS), a further reduction in HDL cholesterol concentration results in an increased LDL/HDL ratio in IIb phenotypes. Although HDL cholesterol is normally distributed in controls and type IIa phenotypes, its distribution is skewed to lower values in type IIb. In addition to similar levels of LDL cholesterol, the presence of tendon xanthomatas is equally observed in both type IIa and type IIb subjects (51.1% and 62.5%, respectively). Similarly, the incidence of angina pectoris (19.2% and 12.5% in type IIa and type IIb, respectively) is also approximately the same in both groups. However, the differences are striking in the incidence of myocardial infarction (MI), which is increased three-fold (25% v 8.5%) in type IIb subjects, as compared to type IIa. These findings indicate that in addition to LDL excess, HDL deficiency associated with elevated plasma triglycerides contributes to the severity of ischemic heart disease, as revealed from the manifestation of MI in some FH heterozygotes.

References (38)

C Gagné et al.
Heterozygous familial hypercholesterolemia: Relationship between plasma lipids, lipoproteins, clinical manifestations and ischaemic heart disease in men and women
Atherosclerosis
(1979)
GJ Miller et al.
Plasma high density lipoprotein concentration and development of ischaemic heart disease
Lancet
(1975)
K Hirobe et al.
Coronary artery disease in heterozygous familial hypercholesterolemia
Atherosclerosis
(1982)
V Beaumont et al.
Ischaemic heart disease in men and women with familial hypercholesterolemia and xanthomatosis: A comparative study of genetic and environmental factors in 274 heterozygous cases
Atherosclerosis
(1976)
RP Noble
Electrophoretic separation of plasma lipoproteins in agarose gels
J Lipid Res
(1968)
T Gordon et al.
High density lipoprotein as a protective factor against coronary heart disease: The Framingham study
Am J Med
(1977)
S Eisenberg
High density lipolprotein metabolism
J Lipid Res
(1984)
EJ Schaefer et al.
Plasma triglycerides in regulation of HDL cholesterol levels
Lancet
(1978)
RJ Garrison et al.
Obesity and lipoprotein cholesterol in the Framingham offspring study
Metabolism
(1980)
LA Carlson et al.
Ischaemic heart disease in relation to fasting values of plasma triglycerides and cholesterol
Lancet
(1972)

LA Carlson et al.

Serum triglycerides, to be or not to be a risk factor for ischaemic heart disease

Atherosclerosis

(1981)

H Aberg et al.

Serum triglycerides are a risk factor for myocardial infarction but not for angina pectoris: Results from a 10-year follow-up of Uppsala primary preventive study

Atherosclerosis

(1985)

DS Fredrickson et al.

The familial hypercholesterolemia

J Slack

Inheritance of familial hypercholesterolemia

PO Kwiterovich et al.

Familial hypercholesterolemia (one form of familial type II hyperlipoproteinemia). A study of its biochemical, genetic and clinical representation in childhood

J Clin Invest

(1974)

D Streja et al.

Plasma high density lipoprotein and ischaemic heart disease

Ann Intern Med

(1978)

S Moorjani et al.

Les α-lipoprotéines (cholestérol-HDL) dans la forme hétérozygote de l'hypercholestérolémie familiale

Union Méd Can

(1984)

S Moorjani et al.

Decreased serum levels of high density lipoproteins in familial hyperbetalipoproteinemia associated with early atherosclerosis

RB Goldberg et al.

Abnormalities of high density lipoproteins in homozygous familial hypercholesterolemia

Arteriosclerosis

(1984)

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Although a selective strong elevation in the plasma level of low-density lipoprotein (LDL) cholesterol is the hallmark of familial hypercholesterolemia (FH), also other plasma lipoprotein and lipid subspecies are changed in these patients. Several studies in FH patients have pointed to the qualitative abnormalities of high-density lipoprotein (HDL) particles, including their triglyceride and sphingomyelin enrichment, reduced capacity to promote cholesterol efflux from macrophages, impaired anti-inflammatory and anti-oxidant activities, and reduced plasma levels of miRs regulating HDL-dependent cholesterol efflux from macrophage foam cells, typical of atherosclerotic lesions. Thus, accurate understanding of HDL functionality and its disturbances in FH may serve a better estimation of the prognosis and also provide additional clues when searching for novel therapeutic choices in this disease. In spite of such a potential promise, there has been no prior comprehensive review focusing on indices of HDL function in FH patients. In the present review, we aim to fulfill this gap by identifying measures of HDL function that are impaired in FH, and by providing a concise summary on the impact of different lipid-modifying therapies on HDL functionality in FH.
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Body mass index was calculated by dividing weight by height squared: BMI = kg/m2. Measurements for determining serum lipid-lipoprotein profile were performed using standard procedures [27–29]. Blood analyses were carried out at the Centre hospitalier universitaire de Québec (Quebec City, QC, Canada).
Hypertension is one of the most important risk factors for cardiovascular diseases. The purpose of this study was to evaluate the effect of a cheese naturally enriched in GABA on blood pressure in men with slightly elevated blood pressure. An experimental Cheddar cheese was produced with a starter containing a GABA-producing Lactococcus lactis ssp. lactis strain. A total of 23 men between 23 and 63 years of age consumed 50 g of the experimental cheese (containing 16 mg of GABA) or a placebo cheese daily for 12 weeks. Blood pressure, heart rate, body weight and waist circumference were measured in weeks 0, 2, 4, 6, 8, 10 and 12. Systolic and mean blood pressure decreased in response to the intervention (time effect; p = 0.048 for systolic blood pressure and p = 0.034 for mean blood pressure), but no time-by-treatment interaction was observed. For the experimental cheese, mean blood pressure decreased by 3.5 ± 2.8 mmHg, and systolic blood pressure decreased by 5.5 ± 3.9 mmHg. For the placebo cheese, decreases of 1.6 ± 3.0 mmHg in mean blood pressure and 3.6 ± 4.0 mmHg in systolic blood pressure were observed. No significant change in diastolic blood pressure was observed following the consumption of cheese with or without GABA enrichment.
Plasma HDL-cholesterol and triglyceride levels in familial hypercholesterolemia: Data from the MedPed CZ database and the Czech population
2011, Clinica Chimica Acta
Citation Excerpt :
While the main risk factor for CHD in FH patients is high LDL-C, it may be further increased by low HDL-C and elevated TG [12–14]. At the same time, low HDL-C is considered a typical finding in FH patients [15–18]. However, in our group of FH patients, HDL-C was lower (but still within the normal range), compared with the control population, in the subgroup of FH females without FDB only.
The aim of this study was to compare HDL-cholesterol and triglyceride levels in patients with familial hypercholesterolemia (FH) with a representative sample of the Czech population.
For the FH group: data of 1728 adult patients with FH (600 males and 1128 females) were taken from the MedPed CR database. The control group were 1995 individuals of the population sample of the Czech post-MONICA study (956 males and 1039 females).
Compared with controls, FH males showed higher levels of HDL-cholesterol (1.35 ± 0.35 mmol/l vs. 1.31 ± 0.35 mmol/l; P < 0.05) and triglycerides (1.98 ± 1.00 vs. 1.81 ± 1.45 mmol/l; P < 0.01). After adjustment for age and BMI, the increase in triglycerides remained significant in the subgroup of non-FDB males only (2.22 ± 0.06 vs. 1.74 ± 0.04 mmol/l; P < 0.001). Compared with controls, HDL-cholesterol was lower (1.55 ± 0.40 mmol/l vs. 1.65 ± 0.37 mmol/l; P < 0.001), while triglycerides were higher (1.72 ± 0.82 mmol/l vs. 1.28 ± 0.75, P < 0.001) in FH females. After adjustment for age and BMI, HDL-cholesterol remained lower in the subgroup of FH females without FDB (1.52 ± 0.01 vs. 1.67 ± 0.01 mmol/l, P < 0.001) whereas triglycerides were higher in both female subgroups.
A lower HDL-C in the group of FH patients compared with control subjects was demonstrated in FH females without FDB only. Elevated triglyceride levels were found in FH males and females, except for males with FDB.
Health-At-Every-Size and Eating Behaviors: 1-Year Follow-Up Results of a Size Acceptance Intervention
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Poor long-term success observed with current weight-control strategies stresses the relevance to explore new weight management approaches.
To assess the effects of a Health-At-Every-Size (HAES) intervention on eating behaviors, appetite sensations, metabolic and anthropometric variables, and physical activity levels in women at 6-month and 1-year postintervention.
Randomized controlled trial; measurements at baseline, at the end of the intervention period (4 months), and at 6-month and 1-year postintervention (10 months and 16 months, respectively). Intervention and testing took place from September 2003 to August 2006.
Premenopausal overweight/obese women (n=144; mean age of 42.3±5.6 years), recruited from free-living, general community.
Women were randomly assigned to: HAES group (n=48), social support group (n=48), or control group (n=48).
Eating behaviors (restraint, disinhibition, and susceptibility to hunger), appetite ratings (desire to eat, hunger, fullness, and prospective food consumption), anthropometric and metabolic variables (body mass index, waist and hip circumferences, blood lipid levels, and blood pressure), and engagement in moderate to intense physical activity (energy cost ≥1.2 kcal×kg⁻¹×15 minutes⁻¹ [≥4.8 metabolic equivalents]).
Changes for each dependent variable were assessed by linear mixed models according to a group (HAES vs social support vs control) by time (baseline vs 4 months vs 10 months vs 16 months) split-plot design.
Situational susceptibility to disinhibition and susceptibility to hunger significantly decreased over time in both HAES group (−0.9±0.2 and −1.3±0.5, respectively) and the social support group (−0.4± 0.2 and −1.4±0.5, respectively). Although eating behavior scores observed at 16 months did not differ between HAES and social support groups (situational susceptibility to disinhibition: 2.5±0.2 in HAES group vs 2.7 ± 0.2 in social support group; susceptibility to hunger: 4.2±0.5 in both groups), they were lower in these groups than scores noted in the control group (3.3±0.2 for situational susceptibility to disinhibition and 5.9±0.5 for susceptibility to hunger).
These results suggest that, when compared to a control group, an HAES approach could have long-term beneficial effects on eating behaviors related to disinhibition and hunger. In addition, our study did not show distinctive effects of the HAES approach in comparison to a social support intervention.
Diagnosis of type III hyperlipoproteinemia from plasma total cholesterol, triglyceride, and apolipoprotein B
2007, Journal of Clinical Lipidology
Our objective was to develop a simple algorithm that could be applied in routine clinical practice to diagnose type III hyperlipoproteinemia based on plasma total cholesterol, triglyceride and apolipoprotein (Apo) B.
Analysis of plasma lipid, lipoprotein lipid, and apolipoprotein data from 1771 patients in a tertiary care lipid clinic, from whom all data had been collected prospectively by standardized methods. Of the 1771, based on the Fredrickson classification, 16 had type I hyperlipoproteinemia, 736 type IIa hyperlipoproteinemia, 371 type IIb hyperlipoproteinemia, 38 type III hyperlipoproteinemia, 509 type IV hyperlipoproteinemia, and 101 type V hyperlipoproteinemia.
Mean plasma ApoB was highest in type IIb (1.53 ± 0.36 g/L), borderline high (1.1 ± 0.23 g/L) in type IV, normal in type III and type V (1.04 ± 0.21 g/L and 0.96 ± 0.40 g/L, respectively) and low in type I (0.48 ± 0.16 g/L). In type III hyperlipoproteinemia, very low–density lipoprotein ApoB (ie, d<1.006 g/mL) accounted for 42.3% of total ApoB, a value that was substantially higher than in any of the other dyslipoproteinemias.
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Plasma triglycerides related decrease in high-density lipoprotein cholesterol and its association with myocardial infarction in heterozygous familial hypercholesterolemia

Abstract

Atherosclerosis

Lancet

Atherosclerosis

Atherosclerosis

J Lipid Res

Am J Med

J Lipid Res

Lancet

Metabolism

Lancet

Atherosclerosis

Atherosclerosis

The familial hypercholesterolemia

Inheritance of familial hypercholesterolemia

Familial hypercholesterolemia (one form of familial type II hyperlipoproteinemia). A study of its biochemical, genetic and clinical representation in childhood

J Clin Invest

Plasma high density lipoprotein and ischaemic heart disease

Ann Intern Med

Les α-lipoprotéines (cholestérol-HDL) dans la forme hétérozygote de l'hypercholestérolémie familiale

Union Méd Can

Decreased serum levels of high density lipoproteins in familial hyperbetalipoproteinemia associated with early atherosclerosis

Abnormalities of high density lipoproteins in homozygous familial hypercholesterolemia

Arteriosclerosis