[Show abstract][Hide abstract] ABSTRACT: To determine whether patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) had evidence of increased homocysteine levels compared with non-CADASIL patients with ischemic stroke or transient ischemic attack.
We compared fasting plasma homocysteine levels and levels 6 hours after oral loading with methionine, 100 mg/kg, in non-CADASIL patients with ischemic stroke or transient ischemic attack and in patients with CADASIL. Prechallenge, postchallenge, and change in homocysteine levels between the 2 groups were compared with use of the Wilcoxon rank sum test.
CADASIL and non-CADASIL groups were similar in age (mean, 48.8 vs. 46.5 years, respectively; 2-tailed t test, P=.56) and sex (men, 86% vs 59%; Fisher exact test, P=.12). The 59 patients in the CADASIL group had higher median plasma homocysteine levels compared with the 14 patients in the non-CADASIL group, both in the fasting state (12.0 vs 9.0 micromol/L; P=.03) and after methionine challenge (51.0 vs 34.0 micromol/L; P=.007). Median difference between homocysteine levels before and after methionine challenge was greater in the CADASIL group than in the non-CADASIL group (34.5 vs. 24.0 micromol/ L; P = .02).
Our findings raise the possibility that increased homocysteine levels or abnormalities of homocysteine metabolism may have a role in the pathogenesis of CADASIL.
Mayo Clinic Proceedings 01/2002; 76(12):1213-8. DOI:10.4065/76.12.1213 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the importance of classic and nonclassic risk factors in the development of coronary artery disease (CAD) or cerebrovascular disease (CVD) in patients with type 2 diabetes mellitus (DM).
In this community-based, prospective cohort study, quantitative measurements for cholesterol, triglycerides (TGs), glucose, and lipoprotein(a) detected as a sinking pre-beta-lipoprotein band on electrophoresis were obtained from 1968 through 1982 from 449 patients who were free of CAD and CVD but had type 2 DM. Demographic data and covariables obtained were age, body mass index, duration of diabetes, sex, smoking, and hypertension. The relationship of individual continuous factors to the development of CAD and CVD as well as multivariate models were evaluated with use of the Cox proportional hazards model. The primary outcome was to determine which risk factors are associated with development of CAD or CVD in patients with type 2 DM.
After a mean follow-up of 13 years, 216 CAD and 115 CVD events had developed. The hazard ratio estimates with 95% confidence intervals (CIs) for CAD after multivariate analysis were significant for age, 1.45 (95% CI, 1.27-1.67); fasting glucose levels at enrollment, 1.63 (95% CI, 1.17-2.25); smoking, 1.45 (95% CI, 1.10-1.91); and TGs, 1.49 (95% CI, 1.15-1.92). The hazard ratio estimates for CVD were significant for age, 1.95 (95% CI, 1.59-2.38); hypertension, 1.89 (95% CI, 1.30-2.74); fasting glucose levels at enrollment, 1.69 (95% CI, 1.06-2.70); and smoking, 1.57 (95% CI, 1.07-2.30).
In diabetic patients, age, fasting glucose levels, smoking, and TG levels are independent risk factors for development of CAD events. Age, hypertension, glucose, and smoking predicted development of CVD events.
Mayo Clinic Proceedings 08/2001; 76(7):707-12. DOI:10.4065/76.7.707 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To establish baseline data for the CardioVision 2020 program, a collaborative project in Olmsted County, Minnesota, organized to reduce cardiovascular disease rates by altering 5 health-related items: (1) eliminating tobacco use and exposure, (2) improving nutrition, (3) increasing physical activity, (4) lowering serum cholesterol level, and (5) controlling blood pressure.
Data about tobacco use, diet, and physical activity were collected by random digit dial interview and follow-up questionnaire from a sample of the population. Blood pressure data were collected from medical records at Mayo Clinic, and serum cholesterol data were derived from the Mayo Clinic laboratory database. Data were stratified into 6 age groups.
A total of 624 women and 608 men responded to the questionnaire. Population blood pressure data were available for 1,956 women and 1,084 men. Population serum cholesterol data were available for 17,042 women and 12,511 men. Except for women in the 30- to 39-year-old age group, less than 10% of the population sampled met 4 or 5 goals. Conversely, about 90% of the population met at least 1 goal, and about 80% met 1, 2, or 3 of the goals.
The data from the Olmsted County population indicate considerable opportunity to reduce this population's burden of cardiovascular disease.
Mayo Clinic Proceedings 12/2000; 75(11):1153-9. DOI:10.4065/75.11.1153 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the efficacy of stanol esters in lowering cholesterol in a US population.
After a run-in phase, 318 subjects were randomized to receive one of the following margarine-like spreads containing stanol ester or placebo for 8 weeks: EU 3 G: 1 g of stanol (ester form) per 8-g serving of a European formula 3 times a day; US 3 G: 1 g of stanol (ester form) per 8-g serving of a US reformulation 3 times a day; US 2 G: 0.67 g of stanol (ester form) per 8-g serving of a US reformulation 3 times a day; or placebo spread.
Mean +/- SD baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were 233+/-20 and 153+21 mg+/-dL, respectively. In the US 3 G group, 3 g daily of stanol esters lowered TC and LDL-C levels by 6.4% and 10.1%, respectively. There was a dose-dependent response compared with 2 g daily (US 2 G). Triglyceride and high-density lipoprotein cholesterol levels were unchanged. The incidence of adverse effects was not different from placebo. Serum vitamin A and 25-hydroxyvitamin D levels were not affected.
Stanol esters lowered TC and LDL-C levels in a mildly hypercholesterolemic US population without evidence of adverse effects. It may be a useful dietary adjunct to lower cholesterol.
Mayo Clinic Proceedings 01/2000; 74(12):1198-206. DOI:10.4065/74.12.1198 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clomiphene has been available for clinical use since 1960 and has been successfully used to aid fertility in women with certain anovulatory disorders. It is a synthetic estrogen analog, of the triphenylethylene derivative group, and its biochemical structure is similar to that of tamoxifen. Estrogen and tamoxifen lower total and low-density lipoprotein cholesterol and increase triglyceride and high-density lipoprotein cholesterol levels. In patients with baseline hypertriglyceridemia, these agents can induce severe hypertriglyceridemia and pancreatitis. The actions of clomiphene on lipid metabolism have not been studied, and to our knowledge, no cases of severe hypertriglyceridemia related to the use of clomiphene have been described. We report the case of a woman who developed 2 episodes of clomiphene-induced hypertriglyceridemia and pancreatitis while receiving this drug for treatment of infertility. Given the striking structural similarity between clomiphene and tamoxifen, it is likely that clomiphene is capable of inducing severe hypertriglyceridemia in patients with certain underlying lipid disorders by a mechanism similar to that of tamoxifen.
Mayo Clinic Proceedings 12/1999; 74(11):1125-8. DOI:10.4065/74.11.1125 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The increased risk of coronary artery disease in subjects with diabetes mellitus can be partially explained by the lipoprotein abnormalities associated with diabetes mellitus. Hypertriglyceridemia and low levels of high-density lipoprotein are the most common lipid abnormalities. In type 1 diabetes mellitus, these abnormalities can usually be reversed with glycemic control. In contrast, in type 2 diabetes mellitus, although lipid values improve, abnormalities commonly persist even after optimal glycemic control has been achieved. Screening for dyslipidemia is recommended in subjects with diabetes mellitus. A goal of low-density lipoprotein cholesterol of less than 130 mg/dL and triglycerides lower than 200 mg/dL should be sought. Several secondary prevention trials, which included subjects with diabetes, have demonstrated the effectiveness of lowering low-density lipoprotein cholesterol in preventing death from coronary artery disease. The benefit of lowering triglycerides is less clear. Initial approaches to lowering the levels of lipids in subjects with diabetes mellitus should include glycemic control, diet, weight loss, and exercise. When goals are not met, the most common drugs used are hydroxymethylglutaryl coenzyme A reductase inhibitors or fibrates.
Mayo Clinic Proceedings 11/1998; 73(10):969-76. DOI:10.4065/73.10.969 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elevated lipoprotein(a) [Lp(a)] levels have been associated with the presence of atherosclerotic disease. However, the results of prospective studies of Lp(a) and cardiovascular disease have been contradictory.
From 1968 through 1982, lipoprotein analysis was performed in 11,335 Olmsted County residents. Quantitative cholesterol and triglycerides were obtained along with semiquantitative Lp(a) levels based on electrophoretic pattern. Lp(a) bands were scored from 0 (absent) to 3 (increased). A cohort of 4967 men and 4968 women with no prior history of atherosclerotic disease who had baseline Lp(a) determinations were followed up for 14 years for development of coronary artery disease (CAD) and cerebrovascular disease (CVD). During 131,330 person-years of follow-up, there were 1848 CAD events and 841 CVD events. Age, diabetes, hypertension, cholesterol, and triglycerides were significantly and independently associated with an increased risk of CAD and CVD in men and women. There was a significant increase in the adjusted hazards ratio for CAD with increasing Lp(a) levels for men and women. For Lp(a) level 3, the hazard ratio was 1.9 (range, 1.3 to 2.9) in women and 1.6 (range, 1.0 to 2.5) in men. The adjusted hazard ratio for CVD showed an irregular association with Lp(a) levels in men and no association in women.
In this cohort of 9936 men and women initially free of cardiovascular disease who were followed up for 14 years, Lp(a) was a significant predictor of risk of future CAD. Lp(a) was a weak risk factor for CVD in men and was not a significant predictor of CVD risk in women.
[Show abstract][Hide abstract] ABSTRACT: Bone mass is purportedly reduced by an endogenous or exogenous excess of thyroid hormone or, perhaps, by calcitonin deficiency. Patients who have undergone thyroidectomy could be subject to all of these effects, yet their practical implications in terms of fracture risk are poorly defined. Interpretation is further hampered by the focus on women, where results may be influenced by involutional osteoporosis. Consequently, we assessed the potential for fractures among the 136 Rochester, Minnesota men who underwent thyroidectomy between 1935 and 1979, relative to a group of age-matched control men from the community. With 2194 person-years of follow-up in each group, survival free of any fracture of vertebra, proximal humerus, distal forearm, pelvis, or proximal femur was similar in the two groups (p = 0.23), and the relative risk of any of these fractures for thyroidectomized patients versus their controls was increased only 1.5-fold (95% CI, 0.7-3.2). The difference was entirely accounted for by a statistically significant excess of proximal femur fractures in the men with thyroidectomy. Risk factors for fractures among men with thyroidectomy included greater age at surgery, greater extent of surgery, and the presence of risk factors for secondary osteoporosis. Thus, thyroidectomy, performed mainly for adenoma or goiter, seems to have little overall influence on the risk of age-related fractures in men. However, the association with hip fractures requires further evaluation.
Journal of Bone and Mineral Research 08/1997; 12(7):1092-9. DOI:10.1359/jbmr.1922.214.171.1242 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary artery disease (CAD) is the most common cause of death in women in the United States. Dyslipidemia is a risk factor for CAD in both men and women. Low levels of high-density lipoprotein (HDL) cholesterol and hypertriglyceridemia, especially in association with a dense low-density lipoprotein (LDL) phenotype, may be of greater importance in women than in men. The relationship between CAD and dyslipidemia and the therapeutic approach to disorders of lipid metabolism in women have unique features because of the effects of exogenous and endogenous hormones on lipid pathways. Estrogen decreases LDL cholesterol and Lp(a) lipoprotein and increases triglyceride and HDL cholesterol levels. Progestogens decrease triglycerides, HDL cholesterol, and Lp(a), and they increase LDL cholesterol. Thus, oral contraceptives increase plasma triglycerides, whereas the effect of these agents on LDL cholesterol and HDL cholesterol levels is related to the androgenicity and dose of progestogen. Postmenopausal hormone replacement therapy increases triglycerides and decreases LDL cholesterol. The effect of hormone replacement therapy on HDL cholesterol is influenced by the addition of progestogen. Although no primary prevention studies have analyzed lipid lowering and CAD in women, secondary prevention studies have suggested that the response to drug treatment and the benefit of lipid lowering are similar in women and in men. Hormone replacement therapy should be considered in the treatment of hypercholesterolemia in postmenopausal women; however, individualization of treatment is important to avoid adverse effects.
Mayo Clinic Proceedings 04/1997; 72(3):235-44. DOI:10.1016/S0025-6196(11)64755-1 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether increased Lp(a) lipoprotein levels are associated with either non-insulin-dependent diabetes mellitus (NIDDM) or coronary artery disease (CAD) in patients with NIDDM and to examine the relationship between Lp(a) levels and glycemic control.
We conducted a cross-sectional study of subjects with NIDDM who were participants in the Rochester Diabetic Neuropathy Study and healthy control subjects from the population of Rochester, Minnesota.
Lipids and Lp(a) lipoprotein levels were compared in 227 subjects with NIDDM and 163 control subjects and, among the subjects with NIDDM, in those with (N = 96) and without (N = 131) CAD. The correlation between Lp(a) levels and glycosylated hemoglobin was investigated.
Subjects with NIDDM had higher triglyceride and lower high-density lipoprotein cholesterol levels than did control subjects. Subjects with NIDDM and CAD had higher total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and lower high-density lipoprotein cholesterol levels than did subjects with NIDDM without CAD. Subjects with NIDDM had significantly higher Lp(a) levels than did control subjects, but subjects with NIDDM and CAD did not have significantly higher Lp(a) levels than did those without CAD. Among subjects with NIDDM, the level of Lp(a) was not significantly correlated with glycosylated hemoglobin.
Although subjects with NIDDM have higher Lp(a) levels than do control subjects, Lp(a) does not seem to be associated with CAD in subjects with NIDDM. In this study, no association was found between Lp(a) level and glycemic control.
Mayo Clinic Proceedings 06/1994; 69(5):430-5. DOI:10.1016/S0025-6196(12)61638-3 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether pancreas transplantation alters lipid and lipoprotein concentrations and whether peripheral hyperinsulinemia is always associated with altered lipid levels.
We assessed the lipid profiles of seven pancreas-kidney recipients with insulin-dependent diabetes mellitus, seven kidney recipients without diabetes who received the same immunosuppressive agents, and eight normal subjects.
In the three study groups, fasting and postprandial plasma glucose, insulin, C-peptide, cholesterol, triglyceride, free fatty acid, and apolipoprotein A-I, A-II, C-II, and C-III concentrations were determined.
Fasting and postprandial glucose concentrations did not differ between the two transplant groups; however, peripheral insulin concentrations were twice as high (P < 0.05) in the pancreas-kidney recipients as in the kidney recipients both before (102 +/- 15 versus 53 +/- 6 pmol/L) and after (123 +/- 22 versus 61 +/- 6 nmol/L per 6 hours) ingestion of a meal. Preprandial and postprandial insulin levels in both transplant groups also were greater (P < 0.05) than those in normal subjects (35 +/- 6 pmol/L and 40 +/- 7 nmol/L per 6 hours, respectively). Despite significant differences in insulin concentrations, no differences were noted in total cholesterol, high-density or low-density lipoprotein cholesterol, plasma free fatty acids, or apolipoprotein A-I, A-II, C-II, and C-III concentrations among the study groups. Plasma triglyceride concentrations in the two transplant groups were similar (114 +/- 20 versus 142 +/- 18 mg/dL) and were slightly more than those in the normal subjects (80 +/- 7 mg/dL).
Despite peripheral hyperinsulinemia, pancreas transplantation can result in normal or near-normal lipid and lipoprotein concentrations. Thus, systemic delivery of insulin does not invariably produce an atherogenic lipid profile.
Mayo Clinic Proceedings 03/1994; 69(3):231-6. DOI:10.1016/S0025-6196(12)61061-1 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this paper is to describe a new methodology for the separation of human high-density lipoproteins (HDL) into apolipoprotein (apo) E-poor and apo E-rich subfractions by fast protein liquid chromatography (FPLC) using a heparin affinity column. Recoveries for apolipoproteins AI, AII, CI, CII, CIII, and E were 68.9, 74.7, 71.9, 73.5, 40.0, and 55.8%, respectively. We provide suggestive evidence that apo E-rich HDL is produced from apo E-poor HDL by the displacement of apo AI by apo E. Apo E-poor HDL was the predominant fraction. The molar ratio of apo E to apo AI in apo E-poor HDL was 0.02 and 0.01 for the subjects studied while in apo E-rich HDL it was 1.86 and 1.25. The molar ratios of the C apolipoproteins to apo AI are markedly different between the subfractions.
Journal of Chromatography A 05/1993; 613(2):239-46. DOI:10.1016/0378-4347(93)80138-T · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the influence of exercise on the apolipoprotein (apo) composition of very low density lipoprotein (VLDL) subfractions, we exercised 6 sedentary men for 30 min, 1 h after a fatty meal. VLDL fractions from samples drawn 4, 6 and 8 h post-prandially were separated from pre-stained plasma by high performance liquid chromatography and fractionated to apo E-poor (heparin-unbound) and apo E-rich (heparin-bound) fractions. The postprandial peak area (volts) and apo E, C-II and C-III concentrations (mg/dl) of post-exercise VLDL fractions were compared with corresponding postprandial values obtained at rest. Plasma triglycerides (TG) levels (mg/dl) were significantly lower 4 (P < 0.05), 6 (P < 0.02) and 8 h (p < 0.05) postprandially; the apo E-poor VLDL fraction was not modified by exercise and its apo concentrations were in the low range of detection; the apo E-rich VLDL peak area significantly decreased 4 (P < 0.01), 6 (P < 0.01) and 8 h (P < 0.05) postprandially; the apo E concentration of apo E-rich VLDL was significantly lower 4 (P < 0.02) and 6 h (P < 0.05) postprandially; the apo C-III concentration of apo E-rich VLDL significantly increased, 4 and 6 h postprandially (P < 0.05). Apo E-rich VLDL is, presumably, the metabolically active fraction of the particle and may regulate plasma TG level following exercise. The metabolic role of apo E-poor VLDL remains to be defined.
[Show abstract][Hide abstract] ABSTRACT: We report the occurrence of cytopenia and hypothyroxinemia attributed to decreased levels of thyroxine-binding globulin in patients receiving nicotinic acid. We describe two patients in whom hypothyroxinemia developed while they were taking nicotinic acid; these patients also had decreased levels of thyroxine-binding globulin. Results of all thyroid function tests returned to normal when use of the nicotinic acid was discontinued. In one patient, leukopenia and thrombocytopenia developed during nicotinic acid therapy alone. These conditions were reversed after the drug regimen was discontinued. In another patient, leukopenia and thrombocytopenia developed during combination nicotinic acid and lovastatin therapy. When administration of both drugs was discontinued, the hematologic abnormalities, which could have been due to either nicotinic acid or lovastatin, diminished. We suggest that cytopenia may develop in patients receiving nicotinic acid; thus, thyroid function tests should be interpreted in light of a possible decreased level of thyroxine-binding globulin.
Mayo Clinic Proceedings 06/1992; 67(5):465-8. DOI:10.1016/S0025-6196(12)60393-0 · 6.26 Impact Factor