Decline In Low-density Lipoprotein Cholesterol Research Articles

Multi-trajectories of lipid indices with incident cardiovascular disease, heart failure, and all-cause mortality: 23\xa0years follow-up of two US cohort studies

BackgroundUnderstanding the distinct patterns (trajectories) of variation in blood lipid levels before diagnosing cardiovascular disease (CVD) might carry important implications for improving disease prevention or treatment.MethodsWe investigated 14,373 participants (45.5% men) aged 45–84 from two large US prospective cohort studies with a median of 23 years follow-up. First, we jointly estimated developmental trajectories of lipid indices, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations using group-based multi-trajectory modeling. Then, the association of identified multi-trajectories with incident CVD, heart failure, and all-cause mortality were examined using Cox proportional hazard model.ResultsSeven distinct multi-trajectories were identified. The majority of participants (approximately 80%) exhibited decreasing LDL-C but rising TG levels and relatively stable HDL-C levels. Compared to the individuals with healthy and stable LDL-C, HDL-C, and TG levels, those in other groups were at significant risk of incident CVD after adjusting for other conventional risk factors. Individuals with the highest but decreasing LDL-C and borderline high and rising TG levels over time were at the highest risk than those in other groups with a 2.22-fold risk of CVD. Also, those with the highest and increased triglyceride levels over time, over optimal and decreasing LDL-C levels, and the lowest HDL-C profile had a nearly 1.84 times CVD risk. Even individuals in the multi-trajectory group with the highest HDL-C, optimal LDL-C, and optimal TG levels had a significant risk (HR, 1.45; 95% CI 1.02–2.08). Furthermore, only those with the highest HDL-C profile increased the risk of heart failure by 1.5-fold (95% CI 1.07–2.06).ConclusionsThe trajectories and risk of CVD identified in this study demonstrated that despite a decline in LDL-C over time, a significant amount of residual risk for CVD remains. These findings suggest the impact of the increasing trend of TG on CVD risk and emphasize the importance of assessing the lipid levels at each visit and undertaking potential interventions that lower triglyceride concentrations to reduce the residual risk of CVD, even among those with the optimal LDL-C level.

Fasting plasma glucose and lipid profiles of diabetic patients improve with aerobic exercise training.

This study presents the effects of aerobic exercise training on fasting plasma glucose and lipid profiles (FPG/LP) of diabetic patients in Kumasi. A randomised experimental with control design. The study was conducted at the diabetic unit of KATH in Kumasi, Ghana. Twelve diabetic patients [grouped into intervention (IG) and control (CG)] attending the diabetic unit of KATH with diabetes diagnosis durations less than fifty years, ambulant status/age of 20-68years, sedentary and free from complications. Eight weeks aerobic exercise training between August 2015 and March 2016. Body weight (BW), Body mass index (BMI), fasting plasma glucose (FPG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (T) and total cholesterol (TC). Body weight (4.85kg, 7.0%), body mass index (4.08kg/m2, 7.3%), FPG (5.28mmol/L, 43.5%), LDL-C (.33mmol/l, 11.9%), TC (.47 mmol/l, 5.3%) and T (.48mmol/l, 29.4%) profiles of the patients in IG declined while HDL-C (.11mmol/l, 7.1%) increased. IG patients improved significantly in FPG [6.27 ± 0.91 < 8.00 ± 0.96; t=-52.00, P = 0.000], BW [58.60 ± 15.34 < 75.35 ± 22.00; t= 3.29, P = 0.040] and BMI [23.45 ±5.03<27.04 ±4.78, t=4.24, P = .050] compared to CG. Patients in IG, in addition to conventional care, experienced non-significant decline in LDL-C, TC, T, increase in HDL-C and significant reduction in FPG, BW, and BMI over those receiving conventional care only. Exercise Scientists are recommended to handle exercise sessions for healthcare prevention and management routines of diabetic patients. Not declared.

Substitution of nevirapine or raltegravir for protease inhibitor vs. rosuvastatin treatment for the management of dyslipidaemia in HIV-infected patients on stable antiretroviral therapy (Nevrast study)

Objectives: An observational, prospective, cohort study was performed to compare efficacy and safety of a switch from ritonavir-boosted protease inhibitor (PI/r) to nevirapine or raltegravir with that of rosuvastatin addition to current antiretroviral therapy in HIV-infected patients with hyperlipidaemia.Methods: All HIV-infected patients receiving a stable PI/r-based antiretroviral regimen, with persistently suppressed viremia, naïve to non-nucleoside analogues and to integrase strand transfer inhibitors, with mixed hyperlipidaemia, and who underwent a switch from PI/r to nevirapine (Group A) or raltegravir (Group B) or who started rosuvastatin at 10 mg daily (group C) with unchanged antiretroviral regimen were enrolled into the study.Results: Overall, 136 patients were enrolled: 43 patients were included in the group A, 46 in the group B, and 47 in the group C. The mean age was 46.6 years, and 108 (79.4%) were males. After 48 weeks of follow-up, a significantly greater reduction in the mean low-density lipoprotein (LDL) cholesterol level was reported in group C (-28.2%) than in group A (−10.2%; p < .001) and B (−12.4%; p = .021), while a significantly greater reduction in the mean concentration of triglycerides was observed in group A (−31.2%) and B (−35.5%) than in group C (−11.9%; p = .034 and p = .004, respectively). The incidence of adverse events was <10% and comparable across the three groups.Conclusion: In HIV-positive subjects receiving a PI/r, the initiation of rosuvastatin treatment after 48 weeks yielded a greater decline in LDL cholesterol, while the switch from PI/r to nevirapine or raltegravir led to a greater decline in triglycerides.

Moderate statin treatment reduces prebeta-1 high-density lipoprotein levels in dyslipidemic patients

Elevated plasma levels of prebeta-1 high-density lipoprotein (HDL), the principal acceptor of cholesterol effluxed from macrophages, are associated with increased risk of atherosclerotic coronary heart disease and myocardial infarction. The objective of the study was to assess the effects on prebeta-1 HDL levels of 6-week moderate-dose statin treatment. We studied 101 patients (mean age 52.7years; 53.5% female; 63 with primary hypercholesterolemia; 38 with combined hyperlipidemia) before and after treatment with statins. Mean atorvastatin potency equivalence was 23.6mg/d. Prebeta-1 HDL plasma levels were measured by immunofixation of agarose gels using anti-apolipoprotein A-1 antibody. We observed a 42.0% reduction of low-density lipoprotein cholesterol (181±56 vs 105mg/dL, P<.001). Triglyceride (TG) levels decreased by 22.3% (157 vs 122mg/dL, P<.001), HDL cholesterol levels remained similar (56.0 vs 57.1, P= NS). Levels of prebeta-1 HDL were significantly reduced by 17.9% after statin treatment (mean 11.4 vs 9.4mg apoA-1/dL, P<.001). The magnitude of this decrease was similar with each of 3 statins (atorvastatin, simvastatin, and rosuvastatin). The decrease in prebeta-1 HDL was strongly associated with the decline in TG, but not with the decline in low-density lipoprotein cholesterol. The association of high prebeta-1 HDL with coronary heart disease identifies it as an inferential measure of the rate of cholesterol efflux from the artery wall. Our observations demonstrate a reduction of prebeta-1 HDL with statin therapy, partially reflecting the reduced TGs, and probably reflecting a direct beneficial impact on cholesterol efflux.

Impact of Implementing the 2013 ACC/AHA Cholesterol Guidelines on Vascular Events in a Statewide Community-Based Practice Registry.

Electronic health record data were analyzed to estimate the number of statin-eligible adults with the 2013 American College of Cardiology/American Heart Association cholesterol guidelines not taking statin therapy and the impact of recommended statin therapy on 10-year atherosclerotic cardiovascular disease (ASCVD10 ) events. Adults aged 21 to 80 years in an outpatient network with ≥1 clinic visit(s) from January 2011 to June 2014 with data to calculate ASCVD10 were eligible. Moderate-intensity statin therapy was assumed to lower low-density lipoprotein cholesterol by 30% and high-intensity therapy was assumed to reduce low-density lipoprotein cholesterol by 50%. ASCVD events were assumed to decline 22% for each 39 mg/dL decline in low-density lipoprotein cholesterol. Among 411,768 adults, 260,434 (63.2%) were not taking statins and 103,478 (39.7%) were eligible for a statin, including 79,069 (76.4%) patients with hypertension. Estimated ASCVD10 events were 18,781 without and 13,328 with statin therapy, a 29.0% relative and 5.3% absolute risk reduction with a number needed to treat of 19. The 2013 cholesterol guidelines are a relatively efficient approach to reducing ASCVD in untreated, statin-eligible adults who often have concomitant hypertension.

Secular Trends in Ischemic Stroke Subtypes and Stroke Risk Factors

Early diagnosis and treatment of a stroke improves patient outcomes, and knowledge of the cause of the initial event is crucial to identification of the appropriate therapy to maximally reduce risk of recurrence. Assumptions based on historical frequency of ischemic subtypes may need revision if stroke subtypes are changing as a result of recent changes in therapy, such as increased use of statins. We analyzed secular trends in stroke risk factors and ischemic stroke subtypes among patients with transient ischemic attack or minor or moderate stroke referred to an urgent transient ischemic attack clinic from 2002 to 2012. There was a significant decline in low-density lipoprotein cholesterol and blood pressure, associated with a significant decline in large artery stroke and small vessel stroke. The proportion of cardioembolic stroke increased from 26% in 2002 to 56% in 2012 (P<0.05 for trend). Trends remained significant after adjusting for population change. With more intensive medical management in the community, a significant decrease in atherosclerotic risk factors was observed, with a significant decline in stroke/transient ischemic attack caused by large artery atherosclerosis and small vessel disease. As a result, cardioembolic stroke/transient ischemic attack has increased significantly. Our findings suggest that more intensive investigation for cardiac sources of embolism and greater use of anticoagulation may be warranted.

Ezetimibe and Regression of Carotid Atherosclerosis

There has been recent controversy over failure of ezetimibe to reduce carotid intima-media thickness. Much of this is based on failure to understand important differences among ultrasound phenotypes of atherosclerosis. We analyzed the effect of adding ezetimibe to the regimen of patients being followed in vascular prevention clinics where measurement of carotid plaque burden (total plaque area) is used to guide therapy. There were complete data in 231 patients with total plaque area for 2 years before and 2 years after initiation of ezetimibe. In the 2 years before and after initiation of ezetimibe, total cholesterol decreased significantly before (P<0.0001) and after initiation of ezetimibe (P<0.0001); low-density lipoprotein cholesterol declined significantly before (P<0.0001) and after (P=0.003) initiation of ezetimibe. Triglycerides declined significantly before ezetimibe (P<0.0001) but did not change after addition of ezetimibe (P=0.48). High-density lipoprotein cholesterol did not change significantly before (P=0.87) but declined significantly after ezetimibe (P=0.03). Despite the decline in low-density lipoprotein cholesterol before addition of ezetimibe, there was a significant mean increase in within-individual total plaque area in the 2 years before addition of ezetimibe by 6.89±39.57 mm(2) (SD); after addition of ezetimibe, despite the decline in high-density lipoprotein, plaque area decreased by -3.05±SD 38.18 mm(2) SD (P<0.01). Ezetimibe appears to regress carotid plaque burden. To assess effects of antiatherosclerotic therapies, it is important to measure plaque burden. These findings should be tested in a clinical trial.

Decline in low-density lipoprotein cholesterol concentration: lipid-lowering drugs, diet, or physical activity? Evidence from the Whitehall II study

ObjectiveTo examine the association of lipid-lowering drugs, change in diet and physical activity with a decline in low-density lipoprotein (LDL) cholesterol in middle age.DesignA prospective cohort study.SettingThe Whitehall II study.Participants4469...

Age, obesity and inflammation at baseline predict the effects of testosterone administration on the metabolic syndrome.

Testosterone administration to hypogonadal men improves the metabolic syndrome. This study analyzed whether age, serum testosterone, body mass index/waist circumference, increment in testosterone values and C-reactive protein (CRP) predicted the outcome of testosterone administration. A total of 110 mainly elderly men, aged between 18 and 83years (mean±SD=59.6±8.0) with baseline serum testosterone of 5.8-12.1nmol/L (mean±SD=9.3±1.7) (n>14.0nmol/L), received parenteral testosterone undecanoate whereupon serum testosterone normalized between 3 and 24months. (i) The lower the baseline testosterone, the stronger the decreases in waist size and triglycerides. (ii) The greater the increment in serum testosterone, the stronger the decreases in low-density lipoprotein (LDL) cholesterol, triglycerides and glucose. (iii) Older age was associated with stronger beneficial effects on waist size, glucose and all lipids, but a small negative effect on high-density lipoprotein cholesterol. (iv) Obese men and men with the largest waist circumference showed the strongest declines over 2years in weight, waist circumference and body mass index (BMI), and also in total cholesterol, triglycerides and glucose. Baseline BMI predicted a stronger decline in LDL cholesterol, but a smaller decline in CRP levels. (v) Higher baseline CRP predicted larger declines in levels of triglycerides, glucose and CRP. (vi) In the multivariate model, age, BMI and CRP were independent predictors of the strongest benefit of testosterone treatment on the metabolic syndrome. Older men, particularly when obese with chronic low-grade inflammation benefited most of normalizing their testosterone levels, preferably if they reached mid-normal reference values.

The effect of a garlic preparation on plasma lipid levels in moderately hypercholesterolemic adults

Lipid management is well established as an effective preventive and management tool for cardiovascular disease (CVD). Health claims regarding the cholesterol lowering benefits of garlic are widespread. However, the clinical trial data are inconsistent. The effect of two doses of a commercial garlic preparation on plasma lipids were evaluated, compared to a placebo, in moderately hypercholesterolemic adults (baseline low density lipoprotein cholesterol (LDL-C)=157.4±18.7, mean±S.D.). Fifty-one adults, aged 51.8±8.3 years participated in a double-blind, placebo-controlled, parallel treatment trial conducted in an outpatient research clinic. They were randomized to a placebo or a garlic botanical blend providing 500 or 1000 mg dehydrated garlic powder/day (three groups, 16–18 subjects per group). Plasma lipids were assessed every 2 weeks for 12 weeks. The study was designed with sufficient power to detect a 10% relative decline in LDL-C. The absolute mean changes in LDL-C over 12 weeks were 0.0±4.3, +1.4±4.8, and −10.1±6.8 mg/dl for the placebo, half-dose and full-dose, respectively. In the full-dose group, the LDL-C decrease of 6.1% was not significantly different from the other groups ( P=0.5). No significant differences were observed for total- or high-density lipoprotein cholesterol (HDL-C), or triacylglycerol levels. In conclusion, the garlic powder preparation used in this study among moderately hypercholesterolemic adults did not significantly effect plasma lipids levels. There was no indication of a graded affect by garlic dose over the range of 0, 500 and 1000 mg/day. A small (<10%) effect on LDL-C levels or a threshold effect requiring larger doses are not eliminated by this study.

Suboptimal Outcome of Management of Metabolic Cardiovascular Risk Factors in Hispanic Patients With Essential Hypertension

We studied outcome of management of metabolic cardiovascular risk factors in 155 randomly chosen Hispanic hypertensive patients (mean age, 63 +/- 1 years; 79% female) screened for dyslipidemia. Hypertriglyceridemia (n = 12) or high risk-adjusted low-density lipoprotein cholesterol (LDL-C) (n = 89) was found in 65%. Triglycerides did not change (6.16 +/- 0.58 to 7.44 +/- 2.34 mmol/L; P = NS) over 2.2 +/- 0.5 years. Only 58 patients with high LDL-C were treated, and 8 had no follow-up lipid tests. In the other 50, LDL-C decreased by 10 +/- 3% (P < .001) over 2.8 +/- 0.2 years but attained goal in only 12. In a subset of 24 patients with extended follow-up (3.8 +/- 0.2 years), there was an initial marked decline in LDL-C, followed by a rebound to baseline levels. In 29 of 54 patients with normal LDL-C, lipid testing was markedly overused compared with recommendations. Obesity (n = 94, 61%) did not improve in those with repeated data (+0.6 +/- 0.8 kg; P = NS; n = 40) over 2.7 +/- 0.3 years. Forty-four of 63 patients with type II diabetes had repeated measurement of glycosylated hemoglobin, with no change (10.5 +/- 0.5% to 11.2 +/- 0.5%; P = NS) over 2.2 +/- 0.3 years. Ten-year risk of coronary events (Framingham cohort parametric regression) calculated for 61 patients with known untreated blood pressures (169 +/- 3/98 +/- 1 mm Hg) was 21.0 +/- 1.7%, with a skewed distribution reaching high values (66%) and attributable in large part (72%) to modifiable risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Declining Serum Total Cholesterol Levels Among US Adults

To examine the secular trend in serum total cholesterol levels of the US adult population. Nationally representative cross-sectional surveys with both an in person interview and a medical examination that included the measurement of blood lipid levels. Between 6000 and 13,000 adults aged 20 through 74 years examined in each of four separate national surveys during 1960 through 1962, 1971 through 1974, 1976 through 1980, and 1988 through 1991. Mean serum total cholesterol levels in US adults aged 20 through 74 years have consistently declined over the time period 1960 through 1991. More than half of the decline occurred during the time period 1976 through 1991. This decline occurred across the entire distribution of serum cholesterol levels and in all age-sex groups. High-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels have not changed, suggesting that the decline in total cholesterol levels is due to a decline in low-density lipoprotein cholesterol levels. These results document a continuing and substantial decline in serum cholesterol levels among US adults. They suggest that public health programs, designed to reduce cholesterol levels, are proving successful. The observed downward trend in serum cholesterol levels has coincided with a continuing decline in coronary heart disease mortality. These observations suggest that the Healthy People 2000 goal of reducing the mean serum cholesterol level of US adults to no more than 200 mg/dL (5.17 mmol/L) is attainable.

Effects of casein versus soy protein diets on serum cholesterol and lipoproteins in young healthy volunteers

The effects of casein and soy protein on serum cholesterol levels and lipoprotein composition were studied in 69 healthy volunteers (18 to 28 yr of age) under strict dietary control. Subjects were fed for 6 wk on diets containing 13% of energy as protein, 38% as fat (P/S ratio = 0.6) and about 380 mg cholesterol per day. Of the protein in the diets 65% consisted of casein or soy protein or a 2:1 mixture of casein and soy protein. After a control period of 10 days during which all the subjects received the casein-soy diet, 20 subjects continued on this diet for the next 4 wk as a base-line control, 25 subjects switched to the casein diet, and the remaining 24 subjects switched to the soy diet. Both food records and chemical analysis of double portions revealed that the diets were completely identical except for the type of protein. Average serum cholesterol levels at the end of the control period were 152 +/- 27 mg/dl (3.93 +/- 0.69 mmol/l) and 153 +/- 23 mg/dl (3.95 +/- 0.60 mmol/l) (mean +/- SD) for the casein and soy group, respectively. At the end of the test period the levels were 149 +/- 24 and 150 +/- 23 mg/dl, respectively; thus there was no significant change on either diet. On the casein diet there was no change in the low-density lipoprotein cholesterol concentration, and only a slight, nonsignificant increase in the high-density lipoprotein cholesterol concentration. On the soy diet, however, there was a significant decline in low-density lipoprotein-cholesterol (-6.6 mg/dl; -0.17 mmol/l) and a significant increase in high-density lipoprotein-cholesterol (+5.8 mg/dl; +0.15 mmol/l). The decline in low-density lipoprotein cholesterol in the soy group was significantly different from the small change in the casein group, but the difference in increase in high-density lipoprotein cholesterol in the soy and the casein group was only weakly significant. This suggest that soy protein could have a slight beneficial effect on the distribution of cholesterol over the various lipoprotein fractions, even at constant total cholesterol concentration.

Lipid and lipoprotein distributions in white children ages 6–19 yr. The lipid research clinics program prevalence study

Cross-sectional age- and sex-specific distributions of plasma lipids and lipoproteins are described for 1402 white children ages 6–19 yr. These children were part of a random sample examined at seven lipid research clinics (LRC) during the LRC Prevalence Study, which was established to determine the prevalence of hyperlipidemias and to describe the distribution of lipids and lipoproteins in diverse populations. These populations were not selected to be representative of the entire North American pediatric population. Nonetheless, the large numbers of children in the seven LRC populations and their socioeconomic and geographic diversity do permit analytical and comparative studies of physiological and sociodemographic variables in school-age children. This report of their lipid and lipoprotein levels is one in a series of such studies. Examination of the distribution of plasma lipids and lipoproteins showed that total cholesterol (TCH) and low-density lipoprotein cholesterol (LDL-c) were lower in males than females in most age groups studied. The difference in LDL-c is most marked in the younger age group (ages 6–9 yr) and accounts for most of the difference in TCH concentration at this age. During the adolescent period (ages 10–14 yr) a decline in high-density lipoprotein cholesterol (HDL-c) concentration occurs in the males, but not in the females. This decline continues throughout the postadolescent (ages 16–19 yr) period. The resulting difference in HDL-c mainly accounts for the higher TCH observed in the 16–19 yr-old females. Our study confirms the fall in TCH concentration at about adolescence described previously. However, it highlights the different mechanisms responsible in the two sexes. Whereas in the males the decline in TCH is mainly the result of reduction in the concentration of HDL-c, in the females it is due mainly to a gradual decline in LDL-c.