Untreated Total Cholesterol Research Articles

Defining and Setting National Goals for Cardiovascular Health Promotion and Disease Reduction

This document details the procedures and recommendations of the Goals and Metrics Committee of the Strategic Planning Task Force of the American Heart Association, which developed the 2020 Impact Goals for the organization. The committee was charged with defining a new concept, cardiovascular health, and determining the metrics needed to monitor it over time. Ideal cardiovascular health, a concept well supported in the literature, is defined by the presence of both ideal health behaviors (nonsmoking, body mass index <25 kg/m(2), physical activity at goal levels, and pursuit of a diet consistent with current guideline recommendations) and ideal health factors (untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, and fasting blood glucose <100 mg/dL). Appropriate levels for children are also provided. With the use of levels that span the entire range of the same metrics, cardiovascular health status for the whole population is defined as poor, intermediate, or ideal. These metrics will be monitored to determine the changing prevalence of cardiovascular health status and define achievement of the Impact Goal. In addition, the committee recommends goals for further reductions in cardiovascular disease and stroke mortality. Thus, the committee recommends the following Impact Goals: "By 2020, to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%." These goals will require new strategic directions for the American Heart Association in its research, clinical, public health, and advocacy programs for cardiovascular health promotion and disease prevention in the next decade and beyond.

The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U.K. men

In the present study, we have determined the relative frequency of the R46L, I474V and E670G variants in the PCSK9 (protein convertase subtilisin/kexin type 9) gene and its association with plasma lipid levels and CHD (coronary heart disease) in healthy U.K. men and patients with clinically defined definite FH (familial hypercholesterolaemia). Genotypes were determined using PCR and restriction enzyme digestion in 2444 healthy middle-aged (50-61 years) men from the prospective NPHSII (Second Northwick Park Heart Study), with 275 CHD events (15 years of follow-up), and in 597 U.K. FH patients from the Simon Broome Register. In the NPHSII healthy men, the R46L genotype distribution was in Hardy-Weinberg equilibrium and the frequency of 46L was 0.010 [95% CI (confidence interval), 0.007-0.013], with one man homozygous for the 46L allele. There was significant association of the 46L allele with lower mean (S.D.) total cholesterol [5.74 (1.01) mmol/l for RR compared with 5.26+/-1.03 mmol/l for RL; P=0.001], apolipoprotein B [0.87 (0.24) g/l for RR compared with 0.75 (0.26) g/l for RL; P<0.0001] and low-density lipoprotein cholesterol [4.01 (0.95) mmol/l for RR compared with 3.62 (0.97) mmol/l for RL; P=0.02]) levels, after adjustment for age, general medical practice, smoking, body mass index and systolic blood pressure. As expected, 46L carriers had a low risk of definite or possible CHD [hazard ratio, 0.46 (95% CI, 0.11-1.84)], but this was not statistically significant (P=0.27). Two other common PCSK9 variants I474V [V allele frequency, 0.179 (95% CI, 0.17-0.19)] and E670G [G allele frequency, 0.034 (CI, 0.03-0.04)] were not associated with any significant effects on lipid levels or CHD risk. In FH patients, the frequency of 46L was 0.003 (95% CI, 0.00-0.01), which was significantly lower (P=0.037) than the healthy subjects. In the four FH patients carrying 46L, mean untreated total cholesterol levels were not different (P=0.91) in carriers and non-carriers (median, 10.3 mmol/l compared with 10.2 mmol/l respectively, after adjustment for age, gender and mutation type). In conclusion, the PCSK9 46L allele is more frequent in healthy U.K. men than in FH patients and is strongly associated with a protective plasma lipid profile risk for CHD. Its low frequency (approx. 2% carriers) means that it does not make a major contribution to determining population CHD risk in the U.K.

Can foods with added soya-protein or fish-oil reduce risk factors for coronary disease? A factorial randomised controlled trial

To develop functional foods which are capable of reducing key risk factors for coronary heart disease in an at risk population. The specific hypothesis tested here was that providing bread, cracker biscuits and snack bars fortified with DHA (long-chain omega 3) and soya-protein would havd a positive impact on cholesterol and blood pressure. A pragmatic, double-blind, factorial placebo-controlled randomised trial recruiting 213 middle-aged men and women with untreated elevated total cholesterol or blood pressure. The factors examined were the effect of giving supplies of bread, cereal bars and cracker biscuits fortified with 2 g fish oils (DHA, 22: 6n-3), or 25 g soya-protein (containing 50 mg of isoflavonoids) for five weeks. Primary and secondary outcomes included total, low-density and high-density cholesterol (HDL-C), and systolic and diastolic blood pressure. Compliance was assessed using biomarkers and food intake histories. DHA enriched foods increased HDL-C by 6.0% (95% CI 2.5%, 9.6%) but had no effect on total or low-density cholesterol or blood pressure. Overall, soya-protein did not influence any of the outcomes assessed. However, in women only, soya-protein increased systolic blood pressure by 5.9% (95% CI 1.73, 9.9%). Adding DHA (fish-oils) to staple foods might supplement existing methods to help reduce CVD morbidity and mortality. However, these findings highlight the importance of ensuring that functional foods do not present any harms to particular subgroups within a general population, if they are to be made freely available to consumers. This latter point requires further attention by the research community in relation to soya-protein.

Comparison of prevalence and severity of coronary calcium determined by electron beam tomography among various ethnic groups

Electron beam tomography (EBT) can accurately and noninvasively quantitate the amount of coronary artery calcium (CAC), thus, providing an index of atherosclerotic burden. We sought to evaluate whether ethnic differences exist in the prevalence and severity of coronary calcium in asymptomatic, highrisk patients.  We evaluated 1,426 minority participants (828 men, 598 women) who underwent EBT scanning. These patients were were age- and gender-matched 3:1 with Caucasians (2,484 men, 1,794 women). We utilized the mean age of the minority participants and percentages of men and women to match to our physician-referred Caucasian population. All participants (minorities and matched Caucasians) were asymptomatic and referred by their primary physician to evaluate the presence and amount of CAC. Physicians referred patients to assess their cardiovascular risk. Data on risk factors for coronary artery disease (CAD) were collected at interview before the EBT procedure. The presence and number of risk factors for a participant were calculated based on the National Cholesterol Education Program guidelines. 1 Risk factors included: men aged 45 years, women aged 55 years, current cigarette smokers, history of premature coronary disease in a first-degree relative (men 55 years, women 65 years), diabetes, hypertension, and hypercholesterolemia. Cigarette smoking was defined as smoking 10 cigarettes/day. Participants currently using insulin or oral hypoglycemic agents, or those with dietcontrolled diabetes were classified as diabetic. Systemic hypertension was defined by current use of antihypertensive medication or known and untreated hypertension; hypercholesterolemia was similarly defined by use of cholesterol-lowering medication or known but untreated serum total cholesterol 240 mg/dl. Participants were excluded from the study if they had documented CAD before entry into the study. The study protocol was approved by the institutional review board of the Harbor-UCLA Research and Education Institute. One thousand four hundred twenty-six minority and 4,278 Caucasian subjects at Harbor-UCLA Medical Center underwent EBT using an Imatron C-150XL Ultrafast computed tomographic scanner (Imatron, Inc., South San Francisco, California). Coronary artery visualization was obtained without contrast medium injection, and 30 consecutive images were obtained at 3-mm intervals beginning 1 cm below the carina and progressing caudally to include the entire coronary tree. Exposure time was 100 ms/image slice, and total skin irradiation dose was 600 mrads/ scan. Electrocardiographic triggering was used and adjusted such that image acquisition occurred at the same point in the cardiac cycle starting in late systole.2,3 A computed tomographic threshold of 2 pixels and 130 Hounsfield units was utilized for identification of a calcific lesion. Each focus exceeding the minimum criteria was scored using the algorithm developed by Agatston et al, 4 calculated by multiplying the lesion area by a density factor derived from the maximal Hounsfield unit within this area. A total coronary calcium score was determined by summing individual lesion scores from each of 4 anatomic sites (left main, left anterior descending, circumflex, and right coronary arteries). EBT scoring was performed by a cardiologist who was blinded to the clinical, electrocardiographic, and angiographic information. Categorical data are presented as number (percentages), and continuous data as mean value SD.

Detection and quantitation of calcific atherosclerosis by ultrafast computed tomography in children and young adults with homozygous familial hypercholesterolemia.

Ultrafast computed tomography (CT) is a new method for detecting calcific lesions in the coronary arteries. The ability of CT to detect and quantify coronary artery atherosclerosis in children and young adults at risk for malignant atherogenesis was evaluated. A total of 11 consecutive familial hypercholesterolemic (FH) homozygotes (3 to 37 years old) participated. Untreated total cholesterol concentrations were 488 to 1277 mg/dL (12.7 to 33.2 mmol/L). Angiography detected significant lesions in 7 of 11 patients. CT detected calcific atherosclerosis in all 9 of the patients older than 12 years of age, including all those with angina. CT was more sensitive in detecting aortic root and coronary ostial lesions, where atherosclerosis first appears in homozygous FH. The volume of calcification (in cubic millimeters) correlated with the severity and duration of the hypercholesterolemia (r = .62, P < .05) as well as with the presence of angina (P < .05). All patients with angina (7 of 7) had > 150 mm3 of calcified volume, whereas only 1 of 4 asymptomatic patients had a volume score > 150 mm3. We conclude that (1) coronary and aortic calcium phosphate deposits are common in young FH homozygotes; (2) these deposits are associated with the presence of angiographic stenoses, as has been seen in adults with coronary atherosclerosis; and (3) aortic calcific deposits are more common than calcific coronary lesions.

Human serum gangliosides in hypercholesterolemia, before and after extracorporeal elimination of LDL

Total content, pattern and transport by lipoproteins of gangliosides have been studied in the sera of 10 patients with hypercholesterolemia and manifest cardiovascular disease. Half of the patients with hypercholesterolemia and 3 healthy controls were treated with heparin-induced extracorporeal LDL precipitation (HELP). In the sera of the untreated group total gangliosides and cholesterol were elevated about 2-fold. Ratios of normal ganglioside components were not altered and abnormal ganglioside species not detected. Treatment with HELP resulted in an almost selective removal of lipid-bound sialic acid carried on LDL. The re-increase of total serum gangliosides was strictly correlated to that of LDL-cholesterol and apolipoprotein B. Total gangliosides and ratios of individual components carried on single LDL- and HDL-particles were not altered by the HELP treatment. Our results indicate that gangliosides are excreted into the serum along with nascent apolipoprotein B-containing lipoproteins, which are of hepatic origin. In hypercholesterolemia excretion of gangliosides into the circulation is elevated and surplus of circulating gangliosides is bound to increased numbers of ‘atherogenic’ LDL. Biosynthesis of different ganglioside components, most probably by the liver, and total amount of gangliosides bound to lipoprotein particles seem not to be altered.

Q—T syndrome

Recent guidelines highlight the importance of improving cardiovascular health in the general population in addition to disease prevention among high risk individuals. We investigated factors associated with ethnic and nativity-related differences in the prevalence of low cardiovascular risk (optimal levels of all major cardiovascular risk factors).We used logistic regression to estimate differences in likelihood of being low risk (not currently smoking; no diabetes; untreated total cholesterol < 200 mg/dL; untreated blood pressure < 120/< 80; and body mass index < 25 kg/m2) among 8693 foreign- and U.S.-born Mexican-American and non-Hispanic White 2003–2008 U.S. National Health and Nutrition Examination Survey participants before and after adjustment for socioeconomic, lifestyle, and acculturation-related factors.Foreign-born Mexican-Americans were more likely to be low risk than non-Hispanic Whites after adjustment for all covariates (Odds Ratio [OR]: 1.53; 95% Confidence Interval [CI]: 1.00, 2.34). In contrast, U.S.-born Mexican-Americans were less likely to be low risk compared to Whites (OR: 0.60; 95% CI: 0.43, 0.84). Differences between foreign-born and U.S.-born Mexican-Americans were largely attenuated after adjustment for acculturation indicators.Our findings support the healthy migrant hypothesis and suggest that acculturation-related factors may be important drivers of ethnic and nativity-related differences in low cardiovascular risk.

Proteinuria in patients with malignancies

Recent guidelines highlight the importance of improving cardiovascular health in the general population in addition to disease prevention among high risk individuals. We investigated factors associated with ethnic and nativity-related differences in the prevalence of low cardiovascular risk (optimal levels of all major cardiovascular risk factors).We used logistic regression to estimate differences in likelihood of being low risk (not currently smoking; no diabetes; untreated total cholesterol < 200 mg/dL; untreated blood pressure < 120/< 80; and body mass index < 25 kg/m2) among 8693 foreign- and U.S.-born Mexican-American and non-Hispanic White 2003–2008 U.S. National Health and Nutrition Examination Survey participants before and after adjustment for socioeconomic, lifestyle, and acculturation-related factors.Foreign-born Mexican-Americans were more likely to be low risk than non-Hispanic Whites after adjustment for all covariates (Odds Ratio [OR]: 1.53; 95% Confidence Interval [CI]: 1.00, 2.34). In contrast, U.S.-born Mexican-Americans were less likely to be low risk compared to Whites (OR: 0.60; 95% CI: 0.43, 0.84). Differences between foreign-born and U.S.-born Mexican-Americans were largely attenuated after adjustment for acculturation indicators.Our findings support the healthy migrant hypothesis and suggest that acculturation-related factors may be important drivers of ethnic and nativity-related differences in low cardiovascular risk.