History Of Atherosclerotic Vascular Disease Research Articles

Characterizing the relationship between flow-mediated vasodilation and radial artery tonometry in peripheral artery disease

BackgroundArterial stiffness, measured by the augmentation index (AIX) from radial artery tonometry, and endothelial dysfunction, measured by brachial-artery flow-mediated vasodilation (FMD), have each been associated with increased risk of cardiovascular events. However, their interrelationship in peripheral artery disease (PAD) patients is poorly understood. Materials and methodsIn a cross-sectional analysis of 123 vascular surgery outpatients, the association between FMD and AIX was examined in controls with atherosclerotic risk factors (n = 32) and patients with PAD (n = 91). PAD was defined as claudication symptoms with an ankle-brachial index of <0.9 or a history of revascularization for symptomatic PAD. Controls had an ankle-brachial index ≥0.9 and no history of atherosclerotic vascular disease. ResultsCompared to controls, patients with PAD had lower FMD (6.3 ± 3.8 versus 8.4 ± 3.7, P = 0.008), while central AIX normalized to 75 beats per minute (25.5 ± 9.0 versus 19.3 ± 8.6, P = 0.001) and peripheral AIX (91.3 ± 14.5 versus 81.3 ± 11.4, P = 0.001) were higher. FMD was not significantly correlated with either central or peripheral AIX (central AIX: P = 0.58; peripheral AIX: P = 0.89) across the entire cohort, or in either the patients with PAD (central AIX: P = 0.48; peripheral AIX: P = 0.23) or controls (central AIX: P = 0.43; peripheral AIX: P = 0.92). In a multivariate model including FMD, higher AIX remained independently associated with PAD. ConclusionsIn an analysis of vascular surgery outpatients, no correlation between FMD and AIX was detected. Larger prospective studies are needed to determine whether the inclusion of both parameters improves predictive models for the early identification and potential risk stratification of PAD patients.

Abstract 23077: The Effects Of Prolonged Anacetrapib Therapy On First And Subsequent Occlusive Vascular Events

Background: There is definitive evidence that lowering LDL-cholesterol with statins as monotherapy, or in combination with ezetimibe or PCSK9 inhibitors, prevents not only first but also subsequent major coronary events (i.e. coronary death, myocardial infarction or coronary revascularization). Consequently, prolonged treatment produces greater absolute reductions in morbidity, mortality and economic costs. Inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib lowers LDL-cholesterol levels, as well as substantially increasing HDL-cholesterol, but it is not yet known if it produces benefits on first and subsequent occlusive vascular events and deaths. Methods: The HPS3/TIMI55-REVEAL trial has assessed the effects of adding the CETP inhibitor anacetrapib to atorvastatin on vascular morbidity and mortality in 30,449 individuals who had a history of atherosclerotic vascular disease. Study treatment was continued for a median of 4.1 years. Information was recorded on first and subsequent cardiovascular events that occurred during the scheduled treatment period. Results: The main trial results are to be presented at the European Society of Cardiology Congress in August 2017. For the American Heart Association Congress, it is proposed to present more detailed results on the effects of anacetrapib on first and subsequent occlusive vascular events. Within this high-risk population of individuals with pre-existing vascular disease, 3443 (11%) had a first major coronary event and 1097 subsequent events were reported during the scheduled treatment period. Conclusions: Unblinded results of the cumulative effects of anacetrapib on first and subsequent rates of coronary and other occlusive vascular events will be available for presentation.

Association between arterial stiffness and peripheral artery disease as measured by radial artery tonometry

ObjectiveArterial stiffness and peripheral artery disease (PAD) are both associated with an elevated risk of major adverse cardiac events; however, the association between arterial stiffness and PAD is less well characterized. The goal of this study was to examine the association between parameters of radial artery tonometry, a noninvasive measure of arterial stiffness, and PAD. MethodsWe conducted a cross-sectional study of 134 vascular surgery outpatients (controls, 33; PAD, 101) using arterial applanation tonometry. Central augmentation index (AIX) normalized to 75 beats/min and peripheral AIX were measured using radial artery pulse wave analysis. Pulse wave velocity was recorded at the carotid and femoral arteries. PAD was defined as symptomatic claudication with an ankle-brachial index of <0.9 or a history of peripheral revascularization. Controls had no history of atherosclerotic vascular disease and an ankle-brachial index ≥0.9. ResultsAmong the 126 participants with high-quality tonometry data, compared with controls (n = 33), patients with PAD (n = 93) were older, with higher rates of hypertension, hyperlipidemia, diabetes, and smoking (P < .05). Patients with PAD also had greater arterial stiffness as measured by central AIX, peripheral AIX, and pulse wave velocity (P < .05). In a multivariable model, a significantly increased odds of PAD was associated with each 10-unit increase in central AIX (odds ratio, 2.1; 95% confidence interval, 1.1-3.9; P = .03) and peripheral AIX (odds ratio, 1.9; 95% confidence interval, 1.2-3.2; P = .01). In addition, central and peripheral AIX were highly correlated (r120 = 0.76; P < .001). ConclusionsIn a cross-sectional analysis, arterial stiffness as measured by the AIX is independently associated with PAD, even when adjusting for several atherosclerotic risk factors. Further prospective data are needed to establish whether radial artery tonometry could be a tool for risk stratification in the PAD population.

Family History of Atherosclerotic Vascular Disease Is Associated With the Presence of Abdominal Aortic Aneurysm

Family History of Atherosclerotic Vascular Disease Is Associated With the Presence of Abdominal Aortic Aneurysm

Family history of atherosclerotic vascular disease is associated with the presence of abdominal aortic aneurysm.

We investigated whether family history (FHx) of atherosclerotic cardiovascular disease (ASCVD) was associated with presence of abdominal aortic aneurysm (AAA). The study cohort comprised of 696 patients with AAA (70±8 years, 84% men) and 2686 controls (68±10 years, 61% men) recruited from noninvasive vascular and stress electrocardiogram (ECG) laboratories at Mayo Clinic. AAA was defined as a transverse diameter of abdominal aorta ⩾ 3 cm or history of AAA repair. Controls were not known to have AAA. FHx was defined as having at least one first-degree relative with aortic aneurysm or with onset of ASCVD (coronary, cerebral or peripheral artery disease) before age 65 years. FHx of aortic aneurysm or ASCVD were each associated with presence of AAA after adjustment for age, sex, conventional risk factors and ASCVD: adjusted odds ratios (OR; 95% confidence interval): 2.17 (1.66-2.83, p < 0.01) and 1.31 (1.08-1.59, p < 0.01), respectively. FHx of ASCVD remained associated with AAA after additional adjustment for FHx of aortic aneurysm: adjusted OR: 1.27 (1.05-1.55, p = 0.01). FHx of ASCVD in multiple arterial locations was associated with higher odds of having AAA: the adjusted odds were 1.23 times higher for each additionally affected arterial location reported in the FHx (1.08-1.40, p = 0.01). Our results suggest both unique and shared environmental and genetic factors mediating susceptibility to AAA and ASCVD.

Transthoracic echocardiographic and clinical predictors in first versus recurrent ischemic strokes

Recurrent strokes are more likely to be disabling or fatal than first ever strokes. The aim of the study is to evaluate transthoracic echocardiographic (TTE) and clinical predictors in patients with first versus those with recurrent ischemic strokes. A prospective observational comparative study of 217 patients admitted with ischemic strokes who were in sinus rhythm. Two groups of patients were simultaneously enrolled. The first group was 110 patients with first ischemic stroke and the second was 107 patients with recurrent ischemic stroke. TTE was done for all patients. Both echocardiographic and clinical risk factors were compared between both groups. Logistic regression analysis identified predictors for recurrent strokes. Among clinical risk factors hypertension, hyperlipidemia, family history of atherosclerotic vascular disease, prior coronary artery disease, peripheral vascular disease, and chronic kidney disease were significantly higher in recurrent stroke group. Multivariate logistic analysis identified age (OR, 1.03; 95% CI, 1.01 - 1.07), hypertension (OR, 2.25; 95% CI, 1.03 - 4.92), and hyperlipidemia (OR, 2.73; 95% CI, 1.40 - 5.35), as predictors for recurrent ischemic strokes. Left ventricular diastolic dysfunction, left ventricular hypertrophy (LVH) and aortic sclerosis were significantly more common in the recurrent stroke group compared to the first stroke group. However, in multivariate logistic analysis only LVH (OR, 3.50; 95% CI, 1.69 - 7.23), was identified as a predictor for recurrent strokes. Older age, hypertension, hyperlipidemia and left ventricular hypertrophy are significant predictors of recurrent ischemic strokes in patients with sinus rhythm. Those patients need more aggressive lipid lowering therapy and optimal blood pressure control.

Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)—A randomized placebo-controlled trial

Sodium glucose co-transporter 2 inhibition is a novel mode of treatment for type 2 diabetes mellitus (T2DM). The sodium glucose co-transporter 2 inhibitor canagliflozin lowered blood glucose, blood pressure, and body weight, with increased risk of urogenital infections in Phase 2 studies. Effects on macrovascular complications of diabetes remain to be determined. CANVAS is a double-blind, placebo-controlled trial designed to evaluate the effects of canagliflozin on the risk of cardiovascular disease and to assess safety and tolerability in patients with inadequately controlled T2DM and increased cardiovascular risk. The first of 2 planned phases randomized 4,330 individuals to placebo, canagliflozin 100 or 300 mg (1:1:1) with planned follow-up of about 2 years to substantiate potential cardiovascular protection by assessing key biomarkers and to achieve initial safety objectives. By the end of mid-September 2012, a total of 7174 patient-years of follow-up were accrued. Mean baseline age was 62 years, duration of diabetes 13 years; hemoglobin A1c 8.2%, fasting plasma glucose 9.3 mmol/L, and body mass index 32 kg/m(2). Of the participants, 34% are female and 57% had a history of atherosclerotic vascular disease. Participants will be followed up to achieve primary safety and tolerability objectives and to investigate secondary outcomes. The planned second phase will not be undertaken. CANVAS will define the effects of canagliflozin on biomarkers and provide data on cardiovascular safety against established regulatory parameters.

Risk for Cardiovascular Outcomes among Subjects with Atherosclerotic Cardiovascular Disease and Greater-than-Normal Estimated Glomerular Filtration Rate

Estimating equations for calculating glomerular filtration rate (eGFR) occasionally identify patients with elevated eGFR, yet the prognostic significance remains to be determined. This study sought to define the association of an elevated eGFR on the risk for death and cardiovascular outcomes among subjects with atherosclerotic cardiovascular disease. Data from 8941 subjects who had a history of atherosclerotic vascular disease and were enrolled in the Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion trial were analyzed. Time to the composite end point of death, congestive heart failure, myocardial infarction, or stroke was modeled using Cox proportion hazards regression. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease and Cockcroft-Gault formulas. Compared with subjects with eGFR of 100 to 125 ml/min per 1.73 m2, subjects with eGFR > or = 125 (n = 462) were younger, female, and nonwhite. In addition, subjects with an elevated eGFR were more likely to have diabetes and congestive heart failure. In adjusted analyses, every 10-ml/min per 1.73 m2 decrease in eGFR < 100 was associated with a 13% increased hazard for the composite end point. In addition, every 10-ml/min per 1.73 m2 increase in eGFR > or = 100 was associated with a 9% increased hazard for the composite end point. In individuals with a history of vascular disease, the relationship between eGFR and cardiovascular outcomes may be parabolic, with increased risk among patients with both reduced and elevated eGFR.

An Absorbing Problem

SSESSMENT life-long resident of Baltimore, Maryland, the patient lived here with her husband and children and worked full-time as a uman resources manager. She was a non-smoker and reported o alcohol or illicit drug use. Her only medicine was a multiitamin which she took occasionally. She practiced no dietary estrictions, including red meat. The patient’s past medical istory was significant for 3 uncomplicated vaginal deliveries. er mother had a history of atherosclerotic vascular disease, nd her father and brother were well. None of her 3 children, ges 7, 8, and 12, had any medical history, including iron eficiency. Upon review of her symptoms, the patient reported cravings or ice, restless legs, and fatigue. She described episodes of ightheadedness, occasional left-hand numbness and tingling, nd 1 pre-syncopal episode. She denied gasterointestinal bleedng, menorrhagia, blood transfusion history, pain in her mouth, ietary restrictions or changes, food allergies, weight changes, iarrhea, constipation, dyspepsia, lactose intolerance, nausea, omiting, abdominal bloating or pain, rashes or skin lesions. The physical examination revealed a pale woman in no istress. She was afebrile, blood pressure of 118/63, pulse 76, ormal respirations, and a weight of 56.9 kilograms (125.1 ounds). She was not orthostatic. Her sclera and conjunctivae ere normal. Cardiac exam revealed a normal S1 and S2 and faint systolic ejection murmur. The lungs were clear to

The K121Q polymorphism in the plasma cell membrane glycoprotein 1 gene predisposes to early myocardial infarction.

Elevated plasma cell membrane glycoprotein 1 (PC-1) expression and the frequent PC-1 K121Q polymorphism have recently been associated with insulin resistance. Since insulin resistance represents an important risk factor for atherosclerotic vascular disease and myocardial infarction, we investigated the involvement of the PC-1 K121Q polymorphism in the development of myocardial infarction. We analyzed two independent series of cardiovascular patients at a defined end-point of atherosclerotic vascular disease (those having suffered myocardial infarction) for the PC-1 K121Q mutation by a newly developed mutagenic separated PCR assay. In both patient groups the presence of the Q allele was significantly associated with younger age at the time of first myocardial infarction, suggesting a more rapid progression of endothelial dysfunction. In a multivariate analysis carriers of the 121Q allele from Vienna and from Central Germany exhibited a 2.6- and a 4.2-increased odds, respectively, for suffering myocardial infarction within the first tertile of age (<51 and <48 years, respectively). Our data indicate that the PC-1 121Q allele might predispose independently of other well established risk factors for early myocardial infarction. Testing for the PC-1 K121Q polymorphism might be valuable in patients with a family history of atherosclerotic vascular disease and myocardial infarction.

Apolipoprotein E polymorphism in indigenous Australians: allelic frequencies and relationship with dyslipidaemia.

To determine the apolipoprotein E (apoE) allelic frequencies and the effect of apoE genotype on lipid concentrations in indigenous Australian subjects. Cross-sectional study. 155 indigenous Australians (92 women and 63 men) of mean (+/- standard deviation) age 45 +/- 17 years (SD +/- 50) were recruited without regard to history of atherosclerotic disease, in collaboration with community-based health centres in five indigenous communities in south-east Queensland. For comparison, 113 subjects of European descent and similar age distribution from the Brisbane and Gold Coast regions were also studied. ApoE allelic frequency; apoE genotype; sex; age; diabetes status; body mass index; history of atherosclerotic vascular disease; and concentrations of total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol. The frequency of the apoE4 allele was found to be significantly higher in the indigenous subjects than in the subjects of European descent (P < 0.001). Among indigenous subjects, those with the apoE4 allele tended to have higher triglyceride concentrations and had significantly lower HDL-cholesterol concentrations than those with the apoE3/3 and 3/2 genotypes. ApoE allelic frequency is likely to be one of the cluster of factors contributing to the high cardiovascular mortality of indigenous Australians.

Plasma homocysteine levels in indigenous Australians.

To determine plasma homocysteine levels in indigenous Australians living in urban areas, and the relationship of these levels with other risk factors in this population. Cross-sectional study. 365 urban indigenous Australian subjects, 153 men and 212 women, mean (SE) age 42 (1) years, ascertained without regard to history of atherosclerotic disease, in collaboration with community-based health centres in five indigenous communities in south-east Queensland, 1997-1998. Plasma homocysteine levels, age, sex, smoking history, metformin therapy, history of atherosclerotic vascular disease, serum creatinine level, red cell folate and serum vitamin B12 levels. 89 subjects (24%) had plasma homocysteine levels 15 mumol/L or above. Homocysteine levels were higher in men than in women (men: 14.4 mumol/L; 95% confidence interval [CI], 13.6-15.2; women: 11.9 mumol/L; 95% CI, 11.4-12.5) (P < 0.001); correlated with age (P < 0.001); higher in current smokers (P = 0.02); higher in subjects taking metformin therapy (P = 0.007); and higher in subjects with a history of atherosclerotic vascular disease (P < 0.001). Homocysteine levels were also correlated with serum levels of creatinine (P < 0.001), red cell folate (P < 0.001), and vitamin B12 (P < 0.001). These data indicate that the high plasma levels of homocysteine of Australian indigenous subjects are associated with a history of vascular disease, and correlated with, among other things, smoking, and folate and vitamin B12 nutritional deficiency. These are potentially reversible risk factors, and our data suggest that focusing public health initiatives on these issues may reduce the high prevalence of cardiovascular disease in the Australian indigenous population.

Medical conditions associated with missing teeth and edentulism in the institutionalized elderly.

Several studies have reported the prevalence of medical conditions or investigated the relationships between the oral health status and general health conditions in the elderly. However, the relationship between medical conditions and oral health among the elderly is not well-described. Previous studies have not clearly identified a consistent association between medical conditions and oral health, specifically edentulism and tooth loss. The purpose of this study was to investigate the relationships between medical conditions and oral health, as assessed by edentulism and missing teeth, in an institutionalized elderly population. A systematic sample (n = 175), stratified by age and sex, was drawn from nursing home patients treated by the University of low' as Geriatric Mobile Unit (GMU) team. Data were extracted from GMU dental records, regarding history of medical conditions, medications, dental history, dentate status, and tooth-by-tooth conditions. Mean numbers of missing teeth were significantly higher among those who had a history of atherosclerotic vascular disease, heart failure, ischemic heart disease, and joint disease. Subjects who had a history of atherosclerotic vascular disease, heart failure, ischemic heart disease, and joint disease were more likely to be edentulous than subjects who did not have a history of those diseases. The biological basis for these relationships between dentate status and systemic medical conditions is unclear and warrants further study.

Cholesterol crystal embolization to liver, gallbladder, and pancreas.

We retrospectively studied the clinical features of all 44 patients (35 men, 9 women, mean age 74.5 years) registered with a diagnosis of hepatic, biliary, and/or pancreatic cholesterol crystal embolization (CCE) in the Dutch National Pathology Information System (DNPIS) from 1973 through 1994. Liver CCE was found in 12 (11 autopsies and 1 biopsy), gallbladder CCE in 2 (resection specimens), pancreas CCE in 19 (18 autopsies and 1 biopsy), and both liver and pancreas CCE in 11 (all autopsies) patients. Five patients presented with focal liver cell necrosis, 1 with acalculous necrotizing cholecystitis, 1 with chronic cholecystitis, 10 with necrotizing pancreatitis, and 1 with chronic fibrosating pancreatitis. Four patients died of CCE-induced pancreatitis. Nineteen patients died as a consequence of other CCE sites. These were reported in 37 patients. All patients had a history of atherosclerotic vascular disease. In half the patients a possibly CCE provoking factor (vascular surgery and/or cannulation, anticoagulant treatment) was present. We conclude that liver cell necrosis, cholecystitis, and pancreatitis may be caused by CCE, particularly in elderly male patients with a history of atherosclerosis.

Socioeconomic Status and Carotid Atherosclerosis

There is a consistent body of evidence that socioeconomic status (SES) is importantly associated with cardiovascular morbidity and mortality. However, little information currently exists on the relationship between SES and early manifestations of atherosclerotic vascular disease. We investigated the association between education, income, and occupation and intima-media thickness (IMT) in a population-based sample of eastern Finnish men. Data from the Kuopio Ischemic Heart Disease Risk Factor Study were used to estimate mean IMT across levels of SES in 1140 men. The association between SES and IMT was examined in relation to atherosclerotic risk factors and was also stratified by degree of atherosclerotic progression and was also stratified by degree of atherosclerotic progression and prevalent cardiovascular disease. There were significant, inverse, graded differences between levels of SES and IMT. For education, the age-adjusted mean IMTs for those with primary schooling or less, some high school, and completed high school or more were 0.96, 0.94, and 0.82 mm, respectively. The difference in mean IMT between the most extreme categories of education corresponds to a 15.4% increase in the risk of myocardial infarction. Similar patterns were found for each measure of SES, although the differences between the highest and lowest levels of SES were attenuated by adjustment for risk factors. In men who had no carotid stenosis or nonstenotic plaque and in men who had no indication of prevalent cardiovascular disease, a graded, inverse association between SES and IMT persisted, even after risk factor adjustment. These findings demonstrate a strong association between SES and atherosclerosis in an unselected population. The results show that this association was mediated by known atherosclerotic risk factors, was evident in the early stages of atherosclerosis, and was apparent in a healthy subgroup. Our findings suggest that the impact of SES is evident early in the natural history of atherosclerotic vascular disease.

Management of Atherosclerotic Renal Artery Disease in Younger Patients

From 1970 to 1990, 57 patients 50 years old or younger were treated for hypertension caused by atherosclerotic renal artery disease. Predisposing factors for atherosclerosis included smoking in 43 cases, hyperlipidemia in 15, diabetes in 8 and hyperuricemia in 8. Of the patients 47 had a family history of atherosclerotic vascular disease or a significant related disorder. Evidence of generalized atherosclerosis was present in 55 patients. Atherosclerotic renal artery disease was present unilaterally in 16 cases, bilaterally in 39 and in a solitary kidney in 2.Of the patients 34 were treated surgically, 20 medically and 2 by percutaneous angioplasty. Surgically treated patients experienced significant postoperative improvement in blood pressure (p = 0.001) and renal function (p = 0.05). Medically treated patients experienced significant improvement in blood pressure (p = 0.03) but renal function deteriorated. Younger patients with atherosclerotic renal artery disease suffer from a more severe and accelerated form of atherosclerosis than older patients. Although blood pressure control can be achieved with medical treatment, surgical revascularization offers the best opportunity for stabilization or improvement of renal function.

Cholesterol controversy--where do we go from here? 'Toward healthful diets' reevaluated.

The document, entitled 'Toward Healthful Diets' that was developed by the Food and Nutrition Board of the National Academy of Sciences last year, has again stirred major controversy among the general public and in the medical community regarding the diet-heart hypothesis as a basis for efforts to favorably modify the natural history of atherosclerotic vascular disease in the American population. In this rebuttal to the conclusion drawn in 'Toward Healthful Diets', we review recent evidence in support of the diet-heart hypothesis. We conclude that continued efforts to reduce dietary cholesterol and saturated fat, in the context of efforts to eliminate other reversible risk factors as well, should remain an important goal for individuals and physicians seeking to limit premature death or disability fom atherosclerotic vascular disease.

急性期心筋梗塞と血小板凝集能の意義

Platelet aggregation induced by two concentrations of ADP, fibrinogen, plasminogen and protease inhibitors were examined in 40 acute myocardial infarctions Patients with myocardial infarction were devided into two groups. One group is with past history of atherosclerotic vascular disease such as diabetes mellitus, hypertention and cerebrovascular disease and the other is without past history, of atherosclerotic vascular disease. And these two groups were matched with same age, sex and prognosis. Platelet aggregation and blood factors were compared with two groups, with history of vascular disease and no past history of atherosclerotic vascular disease.1) Platelet aggregation patterns were classified into four types which were type I and II (normal pattern) and type III and IV (hyper aggregability pattern). The platé aggregation of acute myocardial infarction showed normal pattern (type I or II) immediately after attake in both groups but they began to increase 2nd or 3rd day after onset and lasting for ten days. The mean level of platelet aggregation in both groups still remained higher level than healthy persons. This platelet hyper aggregability never return to normal level within one month after attack. Furthermore, platelet aggregation in with past history of atherosclerotic vascular disorder group showed platelet hyperaggregability than in without complication. Fibrinogen and α2-macroglobulin in with complication group were clearly elevated more than non-complicated group. α1-antitrypsin and plasminogen showed no difference between two groups and any increase and decrease was not found in comparison with normal matched controle. Antithrombin III was shown in lower level than normal controle in both groups. And the lowest value of antithrombin III was observed in the group which has past history of atherosclerotic disorders. It is suggested that the decreese of antithrombin III in group which has complication was shown to have more risk to thrombolic complications after attack than in without complication group.

Charge heterogeneity of human low density lipoprotein (LDL).

Plasma samples were obtained from patients with known history of atherosclerosis as well as from a group of Bantus of South Africa and a group of medical students without any history of atherosclerotic vascular disease. The isoelectric point (IEP) of LDL of the different persons was determined by electrophoresis in agarose gel at different pH values. The IEP of the LDL of the students or of the Bantus, were fairly constant at pH 5.28; for the patients the IEP varied widely. The IEP of LDL from hypercholesteremic persons (Fredrickson type II) showed consistently a significantly higher IEP than for the controls. Electrophoretic mobility of the different samples of LDL was determined at pH 6.8 at different ionic strengths using NaCl or CaCl2. The effect of ionic strength (using NaCl) on the mobility was different for LDL isolated from different persons. Low concentrations of CaCl2 reverse the charge of lipoprotein from a negative to a positive one at pH 6.8. The drastic effect of Ca2+ on the net charge of LDL at pH 6.8, possibly due to the exposed phospholipid groups of LDL, shows that this ion may be important in the interaction between the lipoprotein and the mucopolysaccharides; such an interaction has been suggested by other workers as occurring in the arterial wall.