Cases Of Hypercholesterolemia Research Articles

George Lyman Duff Memorial Lecture. Multifactorial etiology of hypercholesterolemia. Implications for prevention of coronary heart disease.

This review underlines the concept that multiple factors are responsible for hypercholesterolemia in the American public. Dietary factors (cholesterol, saturated fatty acids, and obesity) clearly raise the cholesterol level, and they are important causes of borderline-high cholesterol. Still, the unexplained decline of LDL receptor activity with aging contributes importantly to borderline-high levels and cannot be ignored. The loss of estrogen-stimulated LDL receptor synthesis after menopause is an important contributor to elevated cholesterol in postmenopausal women. In addition, several genetic defects inherited singly appear to be responsible for moderate hypercholesterolemia. Some of these defects may represent genetic hypersensitivity to diet, and dietary therapy alone may provide adequate cholesterol lowering. Other defects impart resistance to dietary control, and use of a single cholesterol-lowering drug may be required. With the exception of heterozygous FH, most cases of severe hypercholesterolemia appear to be the result of the coexistence of at least two defects in LDL metabolism, and as a rule, they can be treated successfully only by using cholesterol-lowering drugs in combination.

Stratégie diagnostique et étude des formes secondaires dans une population hypercholestérolémique

Screening for cholesterol was carried out in a cohort of 2400 people. We detected 39 cases (15.7 %) of secondary hypercholesterolemia in a HCT group > 240 mg/dl (10.3 % – 199 F-49 M) : 4 nephrotic syndromes (1.6 % HCT) 2 hepatic deseases (0.8 % HCT), 33 hypothyroidisms (31 F (15.5 %) - 2M (4%), 240–270 mg/dl : 8 (6.4 % HCT–8 % F HCT), > 270 mg/dl : 25 (20.3 % HCT – 23.2 % F HCT). Conclusion : TSH in F group > 270 mg/dl should be systematic.

Physician Reaction to a Local Community Cholesterol Screening Program

One of the primary concerns of the National Cholesterol Education Program about mass screening for elevated blood cholesterol has been the readiness of primary care physicians to deal with a large number of referrals. After 11,680 people were screened in a city of 85,000 people, 3069 (26.3%) were referred to their private physicians. Three months later a questionnaire was mailed to 76 local primary care physicians, and a follow-up letter was mailed to those who had not responded after 2 months. The response rate was 76% from a total of seven specialties, primarily internal medicine and family medicine. Seventy-nine percent of the physicians had been aware of the program, 40% diagnosed at least one case of hypercholesterolemia as a result of the program, and 71% approved of community cholesterol screening. Only one physician indicated that he was overwhelmed with referrals. We conclude that most primary-care physicians support community cholesterol screening as a public health measure and will use screening data to initiate diagnosis.

Immunoglobulin-bound lipoproteins (Ig-Lp) as markers of familial hypercholesterolemia, xanthomatosis and atherosclerosis

In autoimmune hyper- or dislipidemia secondary to a monoclonal antilipoprotein gammapathy, immunoglobulin-lipoprotein (Ig-Lp) complexes are found in the circulating blood. In order to determine their possible significance in common types of hyperlipidemia we compared the Ig-Lp content of sera from 98 healthy blood donors and 155 outpatients from a Lipid Clinic, including 91 cases of hypercholesterolemia (55 familial and 36 non-familial), 15 cases of hypertriglyceridemia, 20 cases of mixed hyperlipidemia and 29 miscellaneous cases. Detection of the Ig-Lp was performed by an ELISA technique with polyclonal affinity purified anti-LDL + HDL as capture antibodies and peroxidase-labeled anti-Ig antibodies specific for IgA, IgG, IgM heavy chains as indicators. Two cases of monoclonal gammapathy (one IgA K and one IgG L) with dislipidemia served as positive controls for the test. IgG, IgA and IgM Lp were found in the sera of the blood donors, in very small quantities when compared with the monoclonal gammapathy cases. All three types of Ig-Lp were also found in the different hyperlipidemic populations studied. When blood donors were compared to hyperlipidemic patients, no difference was observed for IgG Lp. A significant increase in IgM Lp was found in patients with familial hypercholesterolemia ( P < 0.01). An increase in IgA Lp was also found in hypercholesterolemia, familial or not ( P < 0.01), and in patients with corneal arcus ( P < 0.0001), ischaemic disease ( P < 0.01), tendon xanthomas ( P < 0.05) or xanthelasma ( P < 0.05). Furthermore, in a group of 18 paired parents from 9 different families, positive interparent correlations were found for IgM Lp ( r = 0.78; P = 0.013) and IgG Lp ( r = 0.69; P = 0.038). Therefore IgM Lp may be markers for subpopulations of familial hypercholesterolemia, and IgA Lp markers for the risk of atherosclerotic ischemic disease and deposition of lipids in the cornea. It may be (1) that natural clones of autoanti-lipoprotein antibodies are responsible for the minute quantities of Ig-Lp found in normal people; (2) that the marked development of one of these clones is the cause of autoimmune hyper- or dyslipidemia and xanthomatosis associated with monoclonal gammapathy; (3) that the limited development of a clone produces the Ig-Lp particles found in hypercholesterolemic patients; (4) that there are types of Ig-Lp particles (IgA Lp) that may be harmful for tissues independently of hypercholesterolemia.

Serum cholesterol levels in patients with familial hypercholesterolemia confirmed by tissue culture

Sixty-two subjects from 23 families were evaluated by serum lipid analyses and tissue culture biochemistry in skin fibroblasts. In 53 cases from 19 families with proven familial hypercholesterolemia (FHC), fibroblast cultures were successful. In 45 of these cases (85%) the clinical diagnosis of hyper- or normocholesterolemia was in accordance with the tissue culture findings. Four patients, 2–38 years old, had hypercholesterolemia but normal tissue culture results. Four patients, 18–44 years old, had normal serum cholesterol levels for their age and sex, but were heterozygotes according to tissue culture results. In the remaining four families only the propositus had hypercholesterolemia. All members of these families including the propositus had normal tissue culture determinations indicating that not all cases of idiopathic hypercholesterolemia are due to the Goldstein-Brown mechanism of defective LDL receptor function.

The contribution of a health survey to a family practice.

A community health survey provided a family practice in Jerusalem with a considerable amount of new information about its patients, with particular reference to ischaemic heart disease and the major risk factors for atherosclerotic disease. Many previously unknown cases of hypertension and hypercholesterolaemia were revealed among young adults. The survey findings, analysed together with data available in the clinical records of the practice, provided a systematic community picture of the prevalence of risk factors for coronary heart disease; this information has formed the basis for a community medicine programme designed to reduce the risk of these diseases. The survey findings provide base-line data for the subsequent controlled evaluation of this programme.

Increased cholesterol-biosynthesis in familial hypercholesterolemia.

In two cases of idiopathic hypercholesterolemia, aged 6 and 12 years, it was found that in vivo incorporation of sodium acetate-1-14C into serum cholesterol was markedly increased, but that into squalene and lanosterol in serum was less than that in controls. In vitro incorporation of sodium acetate-3H or DL-mevalonic acid-2-14C into cholesterol was markedly increased in the liver homogenates from a patient with hypercholesterolemia, but it showed no difference between the patient and controls when skin, adipose tissue, bone marrow cells or leukocytes were used.

Effect of nicotinic acid on plasma lipids in patients with hyperlipoproteinemia during the first week of treatment

Thirteen patients with hyperlipoproteinemia were treated with nicotinic acid. The fasting plasma lipid level was followed before treatment and daily during the first 5 days of treatment with 1 g of nicotinic acid three times a day. After treatment for 1 day the average triglyceride level was significantly reduced, whilst the cholesterol concentration was unaffected. The triglycerides then remained fairly stable at this new level. The cholesterol level, however, was not significantly reduced until the 4th and 5th days of treatment. The concentration of phospholipids behaved in a similar way to that of cholesterol. These findings suggest that the concentration of the triglyceride-rich very low density lipoproteins (VLDLP) is reduced after 1 day's treatment, whereas the level of the cholesterol and phospholipid-rich low density lipoproteins (LDLP) is not lowered until the 4th to 5th days. This type of lipoprotein change was confirmed by analysis of plasma lipoproteins, separated in the preparative ultracentrifuge, from a case of essential hypercholesterolemia. The following working hypothesis for the action of nicotinic acid on plasma lipids is suggested. Nicotinic acid inhibits mobilization of free fatty acids from adipose tissue. This reduces the uptake of free fatty acids in the liver, which is followed in turn by decreased hepatic formation of VLDLP. The consequences would be reduced conversion of VLDLP to LDLP and, eventually, diminution of the LDLP level in plasma; thus plasma cholesterol and phospholipids would be lowered. Further work is required to confirm this hypothesis and to determine whether nicotinic acid has other effects on fatty acid transport than that of inhibiting lipolysis in adipose tissue.