Borderline High Cholesterol Levels Research Articles

Rare Case of Chronic Limb-Threatening Ischemia in a 32-Year-Old Patient with Nephrotic Syndrome: A Case Report

AbstractChronic limb-threatening ischemia represents the end stage of peripheral artery disease (PAD), primarily affecting individuals over 60 years old. While quite rare, nephrotic syndrome (NS) is recognized for increasing the susceptibility to arterial thromboembolism (ATE). A 32-year-old male complained of resting pain in his left leg and pain after walking 50 meters with his right leg. He had a 9-year history of NS confirmed through biopsy and was on a daily regimen of 2 × 360 mg mycophenolic acid and 1 × 8 mg methylprednisolone. He had no history of hypertension, diabetes, or smoking. Atrophy and ulcers were observed on his left leg. Laboratory tests revealed elevated D-dimer and borderline high cholesterol levels. The right ankle-brachial index was 0.5, and for the left, it was 0.33. Computed tomography angiography identified occlusion in the left external iliac artery and right superficial femoral artery (SFA). The patient underwent percutaneous transluminal angioplasty with a plain balloon on both legs and an additional drug-eluting stent on the left SFA. He was discharged on rivaroxaban, clopidogrel, aspirin, simvastatin, mycophenolic acid, and methylprednisolone, with no complaints. The mechanism behind NS-caused ATE remains unclear, although it is associated with the loss of anticoagulants in urine, increased procoagulant activity, altered fibrinolytic systems, thrombocytosis, and enhanced platelet activation. Prolonged corticosteroid therapy in NS management also amplifies the risk of thromboembolism by promoting a hypercoagulable state. We suspected NS and the prolonged use of corticosteroids as risk factors for ATE, manifested as PAD in our patient. While optimal NS therapy may reduce the risk of PAD, prolonged corticosteroid use should be closely monitored.

The cholesterol-lowering effect of unripe Rubus coreanus is associated with decreased oxidized LDL and apolipoprotein B levels in subjects with borderline-high cholesterol levels: a randomized controlled trial

BackgroundRubus coreanus (R. coreanus) possesses properties that may decrease cholesterol levels.MethodsThe effects of unripe R. coreanus (uRC) consumption on low-density lipoprotein (LDL) and total cholesterol levels related to decreased circulating apolipoprotein (Apo) B and oxidized LDL levels were evaluated. This randomized, double-blind, placebo-controlled study included subjects with borderline-high cholesterol levels (between 200 and 239 mg/dL) who consumed one capsule daily containing 600 mg of freeze-dried uRC extract (n = 39) or the placebo (n = 38).ResultsAfter 12 weeks, the uRC group showed reductions of 21.23 ± 4.36 mg/dL in total cholesterol levels (P = 0.007) and 15.61 ± 4.16 mg/dL in LDL cholesterol levels (P = 0.032). In addition, significantly greater reductions in Apo B levels were observed in the uRC group (− 3.48 ± 3.40 mg/dL), but Apo B levels were increased in the placebo group (6.21 ± 2.84 mg/dL; P = 0.032). Furthermore, a remarkably lower oxidized LDL level was detected in the uRC group (57.76 ± 2.07 U/L) than in the placebo group (66.09 ± 3.47 U/L) after 12 weeks of consumption (P = 0.044).ConclusionsBecause of its cholesterol-lowering effect, uRC shows great promise as a therapeutic agent for subjects with borderline-high total blood cholesterol levels.Trial registrationClinicalTrials.gov Identifier: NCT03649620 (8/28/2018, retrospectively registered).

Lipid profile abnormalities in newly diagnosed type 2 diabetics: a cross-sectional study

Background: India is fast becoming the diabetes capital of the World. A direct atherogenic effect of triglyceride rich particles has been noted. This study assesses the lipid profile abnormalities in newly diagnosed type 2 diabetes mellitus. Since dyslipidemia is a risk factor for cardiovascular disease, such assessment will enable better recognition, prevention and management of cardiovascular mortality and morbidity.Methods: The study was conducted over a period of one year at a tertiary care hospital in South India. A cross-sectional study of 100 newly diagnosed type 2 diabetics in a rural South-Indian population was done. Results: In our study, 55 (55%) participants had high triglycerides and 45 (45%) had normal triglycerides. Among the 55 participants with abnormal triglycerides, 34% had borderline high levels (150-199mg/dl), 18% had high levels (200-499 mg/dl) and 3% participants had very high triglycerides (≥500 mg/dl). 26% male and 29% female participants had above normal triglyceride levels. In our study, 25% had borderline high cholesterol levels and 5% had high total Cholesterol. 39% of participants had near optimal levels of LDL, 19% had borderline high levels of LDL, 7% had high levels of LDL and 4% had very high levels of LDL. Significantly higher levels of triglycerides and LDL were noted.Conclusions: Deranged lipid profiles are quite prevalent in type 2 diabetics with females having higher triglyceride levels. Recognition of such elevated triglyceride levels in even newly diagnosed type 2 diabetics will help in better prevention of associated cardiovascular disease.

Efforts in Hypercholesterolemia Treatment Using Turmeric (Curcuminoid) Extract Phytotherapy on Obese Patients: Preclinical Study

Hypercholesterolemia is an escalation in total cholesterol levels in the blood which can cause various cardiovascular diseases, hypertension, and stroke. Obesity is one of the risk factors of hypercholesterolemia. Turmeric extract (a curcuminoid) therapy including phytotherapy can be used to overcome hypercholesterolemia. This research aims to identify hypercholesterolemia with turmeric extract for obesity patients. The method used in this research was quasi-experimental with one group pretest and posttest design. The sampling technique used in this research was purposive sampling. The research subjects consisted of 18 respondents who met the criteria of hypercholesterolemia (total cholesterol> 200 mg/dl) or with obesity who had a body mass index (BMI)> 25 kg /m²) and they were not taking cholesterol-lowering drugs. Subjects were given turmeric extract with a dose of 1 gram/day for 28 days. Before and after the intervention, total cholesterol levels of respondents were examined. Data analysis was done by using t-paired test. The results showed that the average total cholesterol level before the patient was given turmeric extract therapy was 234.44 mg/dl and 202.06 mg/dl after the treatment. There was a significant decrease in the average cholesterol level after they were given turmeric extract therapy with p-value 0.0001 (ɑ <0.05). The results showed that there was a significant decrease in cholesterol levels, although it was still included in the category of borderline high cholesterol levels. Researchers suggest that respondents continue their turmeric extract therapy with a low cholesterol diet until their total cholesterol levels achieve the normal state.

Patients' Perspectives on Nonadherence to Statin Therapy: A Focus-Group Study

Nonadherence to statin therapy is associated with poor cardiovascular outcomes. We explored factors and perceptions that contribute to statin therapy nonadherence. We conducted a qualitative study that was based on three patient focus groups using a structured discussion guide to explore factors related to statin therapy nonadherence, information sources, perceptions of statins and cardiovascular risks factors, and suggestions for improving adherence. We enrolled 18 adult patients of an integrated delivery system who had been newly prescribed a statin between November 2006 and August 2007, with a subsequent one- to six-month gap in drug supply as documented by automated pharmacy data. We performed content analysis of verbatim focus-group transcripts to assess themes within each domain. Study participants identified many factors that contributed to their statin therapy nonadherence, including concerns or experiences with adverse effects, uncertainty about the benefits or importance of statins for their overall health, and lack of convenience. Concerns about the adverse effects of statins were a dominant theme. Although most participants believed that having a high cholesterol level is unsafe, many were unsure about their personal need for statins if they were making other lifestyle changes or had only borderline high cholesterol levels. Participants suggested that systematic follow-up, as well as greater information about the risks and benefits of statins and the merits of alternative approaches for lowering cholesterol, could have improved their adherence to therapy. Many patients reduced statin use because of concerns about adverse effects and desire for more information about statins. Effective interventions that address patients' underlying concerns and perceptions are needed to improve statin therapy adherence.

Interaction between serum cholesterol levels and the renin–angiotensin system on the new onset of arterial hypertension in subjects with high-normal blood pressure

To investigate the possible interactions between serum cholesterol levels and the renin-angiotensin system on the development of stable hypertension in subjects with high-normal blood pressure (BP). Hypercholesterolemia increases angiotensin-II type 1 (AT1) receptor density and pressor responsiveness to angiotensin II, and has been reported to contribute to the development of hypertension. The effects of elevated serum cholesterol levels on BP control might be exaggerated by concomitant activation of the renin-angiotensin system, and their combination might contribute to the development of stable hypertension. We investigated the relationship between serum cholesterol levels, plasma renin activity (PRA) and the long-term development of hypertension in 66 young (age < 45 years) patients with high-normal BP and elevated (> 200 mg/dl, n = 46: HC) or normal (</=200 mg/dl, n = 20: NC) serum cholesterol levels and in 20 normotensive, normocholesterolemic controls (C). The main outcome measure was the prospective evaluation of the 15-year incidence of stable hypertension in the different populations. New-onset hypertension was higher in patients with high-normal BP and HC when compared to NC patients [relative risk (RR) = 1.9; 95% confidence interval (CI), 1.1-4.3, P < 0.001] and control subjects (RR = 3.1; 95% CI = 1.4-5.3, P < 0.001). High PRA increased the overall rate of hypertension in both HC and NC. The interaction between HC and PRA was more evident in patients with borderline high cholesterol levels (200-240 mg/dl) where the adjusted relative risk of new onset of hypertension was 2.17 (95% CI 1.2-3.74; P < 0.05) in high PRA subjects and 1.17 (95% CI 0.67-2.23; P = 0.87) in subjects with normal PRA. We support the hypothesis that the presence of hypercholesterolemia can promote the development of stable hypertension through its interaction with the circulating renin-angiotensin system in patients with high-normal blood pressure.

Aspirin and thrombinogenesis

Aspirin (ASA) not only inhibits platelet function, but increase in the rate of factor Va inactivation [12]. In patients also exerts additional anticoagulant actions. These actions are coupled with prevention of platelet activation by thromboxane (TX) A2, because only activated platelets are the source of prothrombinase and tenase complexes on their surface. Thus, ASA decreases thrombin formation in vitro and in vivo, in blood emerging from small skin incisions [1,2]. Yet, some patients experience recurrent arterial thrombotic events despite long-term preventive ASA therapy. Various reasons may lead to such episodes, one of them being so-called ASA resistance [3]. This phenomenon is still poorly defined; it could include the clinical inability of ASA to protect patients from cardiovascular events, as well as the failure of ASA to inhibit platelet function in a laboratory test system (e.g. platelet aggregation) [4], or to suppress overall TXA2 production [5]. There are at least two possible explanations for the ASA resistance phenomenon. One is hypercholesterolemia, probably by its virtue to change the physico-chemical properties of the platelet cell membrane [6]. Thus, cholesterol and atherogenic lipoproteins may increase platelet aggregability and TXA2 production [7,8], and support assembly of the prothrombinase complex and thrombin generation [9]. In patients with markedly elevated and borderline high cholesterol levels, ASA in a commonly used doses (75–300 mg/day) has negligible effect on thrombin formation, as measured by microquantitative analytical technique, at the site of microvascular injury [10,11]. On the other hand, 3 months treatment of such patients with simvastatin significantly depresses blood clotting in vivo, mainly through a reduction in thrombin generation [10,11]. Here, statin treatment seems to interfere with several interconnected steps leading to thrombin formation. They include the reduction in the rates of prothrombin activation, factor Va generation, fibrinogen cleavage, factor XIII activation, and a parallel

Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia

Aims: Beneficial effects of statins in preventing cardiovascular events may depend, at least in part, on their anti-inflammatory action. The aim of the study was to assess the influence of simvastatin and aspirin on serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in hypercholesterolemic subjects. Methods and results: In 33 asymptomatic men with total cholesterol (TC) >6.5 mmol l −1 and in 25 men with coronary heart disease and borderline-high cholesterol levels (between 5.2 and 6.5 mmol l −1) chronically treated with low-dose aspirin (75 mg/d), serum levels of CRP, TNF-α, IL-6, and IL-8 were determined before and after a 3-month simvastatin therapy (20–40 mg daily). In the former group, these markers of inflammation were also measured before and after a 2-week treatment with aspirin (300 mg/d), implemented prior to and in combination with simvastatin. A distinct reduction of CRP and TNF-α was found in both groups; IL-6 levels were decreased only in subjects with marked hypercholesterolemia. Aspirin had no effect on the anti-inflammatory action of simvastatin. Conclusions: In men with hypercholesterolemia simvastatin treatment lowers serum levels of CRP and proinflammatory cytokines. Low-dose aspirin does not add to the anti-inflammatory action of simvastatin.

Treatment with Simvastatin and Low-dose Aspirin Depresses Thrombin Generation in Patients with Coronary Heart Disease and Borderline-high Cholesterol Levels

Aspirin and statins are beneficial in coronary heart disease across a broad range of cholesterol levels. We assessed the effects of low-dose aspirin (75 mg daily) on thrombin generation in patients with coronary heart disease and average blood cholesterol levels. We also investigated whether in patients with borderline-high cholesterol level who have been already taking aspirin, additional treatment with simvastatin would affect thrombin generation. Seven-day treatment with low-dose aspirin decreased thrombin generation ex vivo only in patients with total cholesterol < or = 5.2 mmol/L. In patients with higher cholesterol levels aspirin had no effect. In these patients, already taking low-dose aspirin, additional three-month simvastatin treatment resulted in a reduction of thrombin generation. This demonstrates that low-dose aspirin depresses thrombin generation only in subjects with desirable blood cholesterol levels, while in others, with borderline-high cholesterol, thrombin formation is being reduced following the addition of simvastatin.

Five familial hypercholesterolemic kindreds in Japan with novel mutations of the LDL receptor gene.

In the course of investigations of familial coronary artery disease in Hokkaido, the northern island of Japan, we identified five families in which multiple members showed elevated plasma levels of low-density lipoprotein (LDL) cholesterol. To determine the genetic etiology of their lipoprotein abnormalities, we screened DNA samples from these families for mutations in all 18 exons and the exon-intron boundaries of the LDL receptor (LDLR) gene. Novel point mutations were identified in each family: (1) a C-to-A transversion at nucleotide 285, causing a nonsense mutation at codon 74, in eight members of family A; (2) a G-to-A transition at nucleotide 1136, causing substitution of Tyr for Cys at codon 358, in six members of family B; (3) a C-to-T transition at nucleotide 1822, causing substitution of Ser for Pro at codon 587, in five members of family C; (4) a one-base insertion of G to a five-G stretch at nucleotides 1774-1778 (codons 571-572), causing a frameshift, in six members of family D; and (5) a one-base deletion of T at nucleotide 1963-1964 (codon 634), causing a frameshift, in three members of family E. Through the molecular genetic approach a total of 28 individuals in these families were diagnosed unequivocally as heterozygous for the respective LDLR mutations. This method also helped us to diagnose familial hypercholesterolemia, or to exclude from carrier status, 11 children with borderline high cholesterol levels.

National cholesterol treatment guidelines in Korean population--setting-up the cutpoints for high blood cholesterol.

National Cholesterol Treatment Guidelines are different according to race and country, and change year by year, because the distribution of lipid and lipoprotein levels are different by genetic background, dietary habit and life style. So it is mandatory to set-up the national cholesterol treatment guidelines based on the epidemiologic results. To establish the cutpoints for hypercholesterolemia specific to the Korean population, we selected the laboratories, whose inaccuracies of cholesterol measurement were less than 5%, in the external laboratory quality assessment survey, and performed epidemiological survey on the distribution of cholesterol levels, and other risk factors of coronary heart disease (CHD). As a result, prevalence of CHD risk factors was very high in hypertension (28.0%) and relatively low in diabetes (2.8%). Smokers were 42.6% of total subjects. Thirteen percent of subjects had a family member(s) who was suffering from or had of hypertension, stroke, and heart diseases. The average cholesterol level of a Korean was 187 mg/dL, which was about 25 mg/dL lower than that of United States. The 75th percentile to total cholesterol was 210 mg/dL and 90th percentile 235 mg/dL. The cutpoint for borderline-high cholesterol levels provide a major guideline for initiation of dietary and exercise therapy. We propose the cutpoint for borderline-high cholesterol levels as 200 instead of 210 mg/dL to initiate more active dietary and exercise therapy, and we also propose the temporary cutpoint for high blood cholesterol levels as 240 mg/dL instead of 235 mg/dL, which is a reasonable cutpoint considering medical insurance policy of the country. In conclusion, we suggest the cutpoints for borderline-high and high serum cholesterol levels as 200 and 240 mg/dL, respectively.

Lipoprotein Lipids and the Prevalence of Hyperlipidaemia in Rural India

The prevalence of hyperlipidaemias has been inadequately studied in rural populations of developing countries. No significant data exist on the population levels of serum cholesterol, cholesterol subclasses or triglycerides in these countries. We studied fasting blood samples of 300 apparently healthy adults (202 men and 98 women, age range 20-73 years) randomly selected from a larger sample of 3148 individuals during a comprehensive cardiovascular risk-factor survey in Rajasthan, India. Levels of serum total cholesterol, its subfractions [low-density-lipoprotein (LDL) cholesterol, very-low-density-lipoprotein cholesterol and high-density-lipoprotein (HDL) cholesterol] and triglycerides were measured and correlated with age and anthropometric data. The mean +/- SD serum total-cholesterol levels were 4.39 +/- 1.0 mmol/l in men and 4.37 +/- 1.0 mmol/l in women, the mean LDL-cholesterol levels 2.51 +/- 1.0 mmol/l in men and 2.62 +/- 0.9 mmol/l in women, the mean HDL-cholesterol levels 1.15 +/- 0.4 mmol/l in both mean and women and the mean fasting serum triglyceride levels 1.63 +/- 0.6 mmol/l in men and 1.48 +/- 0.7 mmol/l in women. Age correlated positively with total-cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride levels in both men and women. Levels of the cholesterol subtypes did not differ between the sexes (P > 0.01), although triglyceride levels were significantly higher in men (P < 0.01). Lipoprotein lipids did not correlate significantly with height, weight, body-mass index or waist:hip ratio. When classified according to the recommendations of the US National Cholesterol Education Program for the determination of the prevalence of hyperlipidaemia, 43 individuals (14.3%; men 14.4% and women 14.3%) had borderline high cholesterol levels (5.20-6.18 mmol/l) and 24 (8%; men 7.9% and women 8.2%) had high cholesterol levels (> or = 6.21 mmol/l). Forty-five participants (15%) had borderline high LDL-cholesterol levels (3.36-4.11 mmol/l) and 20 (6.7%) had high LDL-cholesterol levels (> or = 4.14 mmol/l); low HDL-cholesterol levels (< 0.9 mmol/L) were found in 89 (29.7%). Eighteen participants (6%) had mild hypertriglyceridaemia (2.82-5.64 mmol/l) and two (0.7%) had severe hypertriglyceridaemia (> 5.64 mmol/l). Total-cholesterol and LDL-cholesterol levels are low in a rural Indian population, although an atherogenic lipid profile is present in a significant proportion.

Clinical application of deoxyribonucleic acid markers in a Utah family with hypercholesterolemia

The manifestation of coronary artery disease (CAD) depends on the interplay of genetic and environmental factors. 1 Deoxyribonucleic acid (DNA) markers should become practical clinical tools for examining the genetic components of CAD. With this in mind, we assessed the use of DNA markers in familial hypercholesterolemia. Many different DNA mutations of the low density lipoprotein receptor gene on chromosome 19 cause familial hypercholesterolemia. 2 Familial hypercholesterolemia is a prevalent autosomal trait characterized by elevated levels of plasma low density lipoprotein cholesterol and early CAD. Heterozygotes have serum cholesterol levels >300 mg/dl and affected men often develop CAD by the fifth decade of life. 2 Restriction fragment length polymorphisms are DNA variations that are detected by Southern blotting. 3 DNA differences between people show up as different sized allelic bands on autoradiograms of Southern blots. Investigators can follow a gene's inheritance by studying the pattern of allelic bands within families of interest. 3 If a DNA marker appears consistently with the disease in affected family members, then DNA variation at the marker locus is said to be linked with the disease. 3 Once linkage with a genetic locus is established, secondary influences on the disease such as diet or exercise can be examined. In this study, we report an 8-generation Utah kindred with many members affected with familial hypercholesterolemia. We found that the familial hypercholesterolemia phenotype was due to a mutation at the low density lipoprotein receptor gene locus. A wide discrepancy in the age of coronary deaths among gene carriers suggested the influence of other genetic or environmental factors. The DNA markers also helped to diagnose as normal a child with borderline high cholesterol levels clinically suspected to have familial hypercholesterolemia.