Endocrinology:
Edited by Lois Jovanovic, MD, Endocrinologist and Diabetologist.
Contents: Lipids | Pituitary | Parathyroid | Adrenal | Steroids | Aldosterone | Diabetes Mellitus | Hypoglycemia | Obesity | Hirsutism | Thyroid | D. Insipidus | Gynecomastia | Various & MEDS | Osteoporosis | Male Hypogonadism | Growth & Puberty | Metabolic Syndrome-X & Hyperglycemia | Preamble-Abbrev | Last updated on 07 May 2012 by http://clinicalmedconsult.com/.
Functions:
Regulate cellular activity for:
1. Metabolism. 2. Growth.
3. Development. 4. Homeostasis.
5. Reproduction.
Hormones: Chemicals derived from amino acids, lipids (e.g., steroids) and peptides are produced by and released from cells and trigger a response in same or other cells by binding to receptors (located inside or outside of cell).
Three major types:
1. Local hormones (cytokines): Released into interstitial fluid (e.g., prostaglandins, histamines, growth factors).
a. Autocrine: Same cell is affected.
b. Paracrine: Neighboring cells affected.
2. Neurotransmitters (Chemical Synapses).
3. Circulating hormones: Released into blood and transported to cells throughout body.
Endocrine Glands:
Although every cell may release hormones, certain areas of the body serve as principal endocrine glands that release circulating hormones, resulting in numerous, complex responses by target cells. Hormone actions in general are regulated by negative feedback systems.
Laws of Endocrinology:
• If you wish to test for hyposecretion of a hormone, try to stimulate it.
• If you wish to test for hypersecretion of a hormone, try to suppress it.
• Random hormone levels are not always helpful; many are pulsatile. and diurnal.
Cholesterol (Lipid Disorders):
Links: Intro & ICD9 | Formulas & Ratios | Goals | Tx Strategies & Summary | Dietary | Bile Acid Sequestrant | Ezetimibe (Zetia) | Statins | Niacin | Fibrates | Combo Meds | Arteriosclerosis | Fredrickson Classification & Skin Findings | Ddx Lipid Components | Lipoprotein / Chol Sub-types & & Advanced Lipidology | Homocysteine | Metabolic Syndrome-X | Elderly pt’s | Children & Adolescents | Omega-3 fatty acids (Fish oil) |
High cholesterol generally means elevated LDL. High triglycerides means elevated chylomicrons, VLDL or IDL. Dyslipidemia is one of the leading treatable causes of lost healthy life world-wide (Lancet. 2002;360:1347–1360). The prevalence of hypercholesterolemia in the USA adult population is 27% (JAMA 1993;269:3009-14). National surveys indicate that 40% of the people in the US between ages 20-74 years have borderline or greater LDL cholesterol,8 and 17-19% of individuals have high LDL cholesterol (Circulation. 2006;113:e85–e151).The prevalence rate of hypercholesterolemia (total chol >240 mg/dL or >6.2 mmol/L) is 17% in the US and Canada (NEJM 2008;358:1842). Adjusting for baseline prevalence of dyslipidemia, the 30-year risks for a 50yo exceeded 80% for borderline-high LDL, 50% for high LDL, and 25% (women) to 65% (men) for low HDL (Am J Med 2007;120:623-630.e1), 20-50% had or developed a low HDL along with a high LDL level. Coronary heart disease is a leading cause of death in the US, accounting for more than one in five deaths each year, or ~ 500,000 fatalities. Of 6704 asymptomatic subjects aged 45 to 84 years in N. Carolina, the overall prevalence of dyslipidemia was 29.3%, and only 54% were taking lipid-lowering drugs, and of those receiving tx, only 40.6% were controlled to goal (Circulation 2006;113:647-656). ....based on the proven benefits of lipid-lowering therapy for primary prevention, dyslipidemia management should be considered among our highest national healthcare quality improvement priorities. A long-term study on 3277 healthy Finnish businessmen found that low cholesterol levels in middle age (30-45yo) predicted lower mortality and better physical quality of life 39 years later (Cardiol Rev 2006;23:13-19)(each mmol/L increase of baseline Tchol was associated with an increased total mortality risk of 11%). Cholesterol levels are closely linked to cardiovascular mortality, especially among middle-age pt’s, but not to stroke-related deaths (Lancet 2007;370:1829-39)...For every 1 mmol/L decrease in cholesterol, ischemic heart disease mortality dropped by half among pt’s ages 40 to 49, by a third among those 50 to 69, and by a sixth among those 70 to 89 according to a review of observational studies. An analysis of 61 prospective observational studies has failed to find any association of total cholesterol with stroke mortality (Lancet 2007;370:1829-1839). A 10-year analysis of offspring patients in the Framingham Heart Study suggests improvements in lipid profiles, particularly beneficial changes in triglyceride and HDL-cholesterol levels despite an overall increase in BMI (Arch Intern Med 2009;169:279-286).....The findings are counterintuitive....Researchers say they have no certain explanation for these beneficial changes in blood lipid levels....one theory might be based on changes in patterns of food consumption in the US. Recent dietary surveys suggest increased consumption of carbohydrates and a decrease in the consumption of fats, particularly saturated fats. The emergence of the summer sun after a long winter appears to have a positive effect on lipid levels an analysis of data from the PROVE IT-TIMI 22 Study has shown (Am J Cardiol 2009;103:1056-1060).....LDL-cholesterol levels are significantly lower (by 6 mg/d) in summer than in winter. A large, longitudinal cohort study demonstrated a convincing association between short sleep duration and hypercholesterolemia in young women (Sleep 2010;33:956).....Shorter self-reported sleep duration was significantly associated with subsequent hyperlipidemia diagnosis in young women (adjusted odds ratio, 0.85; 95% confidence interval, 0.75–0.96), with a similar but nonsignificant trend in men (AOR, 0.91; 95% CI, 0.79–1.05). Cholesterol levels fluctuate with a womens menstrual cycle, and thus readings should be done at the same time in woman's cycle (J Clin Endo and Metab 2010; online Aug. 10)......The researchers found that as estrogen levels rise, HDL rises (peaking at ovulation) and LDL and triglycerides drop.
ICD-9 Codes: 272.5 lipoprotein deficiencies, 272.0 pure hypercholesterolemia, 272.3 hyperchylomicronemia, 272.5 lipoprotein deficiencies, V77.91 screening for lipoid d/o’s.
How Often Do We Need to Check Cholesterol Levels: Adherent patients with well-controlled cholesterol levels could be monitored every 3 to 5 years (Ann Intern Med 2008;148:656) (average test variation = 7%)….many apparent increases in cholesterol level may be false positive…takes 3 yrs before plausible changes in true cholesterol values could be comparable with the short-term variation (before signal equals noise).
Note: all units in mg/dL to convert mg/dL to mmol/L, you multiply by 0.02586.
Lipids that can be measured without fasting: Total cholesterol and HDL cholesterol. LDL cholesterol is calculated from the fasting triglyceride level and total and HDL cholesterol levels are calculated. Either total and HDL cholesterol, or apolipoproteins (apo A1 and B), fasting or not, are equally accurate to assess vascular disease risk according to 6-year data on 300,000 patients (JAMA 2009;302:1993)....Risks for coronary disease and ischemic stroke were not associated with triglyceride levels, and risk for ischemic stroke was only weakly associated with HDL-C or non–HDL-C levels.....No difference in risk prediction was observed between fasting and nonfasting measurements......considerable effort will be required to change the current culture of lipid management, with its heavy emphasis on LDL-C.
Low Chol: Contrary to previous assertions, low total cholesterol is not a cause of cancer, two separate studies show (Cancer Epidemiol Biomarkers Prev 2009;18:2805-2821).....a lower total cholesterol level may actually reduce the risk of high-grade prostate cancer......Low total cholesterol levels were associated with an 18% higher risk of cancer overall, similar to the increases seen in previous studies.
Cholesterol Ratio: Ratio of total cholesterol to HDL cholesterol: TC/HDL. The goal is to keep the ratio <5:1; the optimum ratio is 3.5:1 (>3.5).
The AHA recommendation is to use the absolute numbers for total blood cholesterol and HDL cholesterol levels rather than the ratio in determining the appropriate tx for pt’s (http://www.americanheart.org/presenter.jhtml?identifier=4503). The total cholesterol/HDL cholesterol and apoB/apoA-1 ratios were also strong predictors of ischemic heart disease in all men, and these two lipid ratios were the strongest lipid predictors in men without cardiovascular disease (Arch Intern Med. 2007;167:1373-1378)…Blood lipid levels, other than total cholesterol, are associated with ischemic heart disease in older men…There was no association between total cholesterol and mortality in the overall cohort, total cholesterol levels were positively associated with IHD mortality in men without prior cardiovascular disease. See Apolipoproteins |
Triglyceride–HDL Ratio and Insulin Resistance: Trig/HDL: A good surrogate markers for identifying insulin resistance in overweight pt’s (Ann Intern Med. 2003;139:802-809)…..The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3 in traditional units) for the trig–HDL ratio. Trig / HDL >3 is consistent with insulin resistance. In African Americans, TG levels and TG-HDL-C ratio are not reliable markers of insulin resistance (Arch Intern Med 2005;165:1395-1400). According to an analysis of 9,500 data sets apo-B/HDL ratio emerged as the strongest correlate (odds ratio 1.177 per 1 mg/dl increment), followed by the total chol or non–HDL /HDL ratio (odds ratio for each 1.070 per 1 mg/dl increment), followed by the trig/HDL (odds ratio 1.033 per 1 mg/dl increment (A Population-Based, Cross-Sectional Comparison of Lipid-Related Indexes for Sx’s of Atherosclerotic Disease. Am J Card 2006;published online 29 August 2006)....neither LDL cholesterol nor the LDL/HDL cholesterol ratio correlated significantly.
LDL:HDL ratio: A study with 9,770 pt's found that those with the lowest LDL:HDL ratios (<1.33) experienced fewer than half as many CV events as those with the highest ratios (2.41) (NEJM 2007 Sep 27; 357:1301).
Formulas:
Total Chol (=TC) = HDL+LDL+VLDL.
Trig/5 =VLDL.
LDL = TC - (HDL+TG / 5). Aim for <130 mg/dL (3.36 mmol/L). For most pt’s, total cholesterol of 240 and 200 mg/dL correspond roughly to LDL of 160 and 130 mg/dL. A non-fasting sample may have higher trig’s and thus falsely lower LDL as well. If the triglyceride values are higher than 4.52 mm/L (> 400 mg/dL), the LDL-C value will be even less accurate. Direct measurement of LDL in a specialized lab, using ultracentrifugation, may be necessary when significant hypertriglyceridemia persists despite fasting.
Non-HDL cholesterol = Total Chol – HDL. Non-HDL-C = the sum of all the cholesterol in the proatherogenic lipoproteins, and apoB, the major apolipoprotein of very low-density lipoprotein, intermediate-density lipoprotein, and LDL particles. Requires no additional cost and is readily available for clinical use. For and LDL-C of <70 mg/dL, the corresponding non-HDL-C goal would be <100 mg/dL.This includes all cholesterol present in lipoprotein particles considered to be arthrogenic (LDL, lipoprotein(a), IDL and VLDL) and is a better predictor of CVD mortality, aim for <190mg/dL (Arch Int Med 2001;161:1413). Non HDL-C and the ratio of Total-C to HDL-C were as good or better than apoliporotein fractions in predictiong future cardiovascular events in 15,632 US women (JAMA 2005;294:326-33). Non-HDL cholesterol accounts for LDL cholesterol plus other atherogenic particles but does not require a fasting sample, suggests that non-HDL cholesterol may be at least as useful as LDL cholesterol to initially screen pt’s for risk of a first nonfatal MI (Am J card 2005;96:1129-1134). Triglycerides and non-HDL cholesterol correlated with large-artery atherosclerosis in a cohort of patients with stroke or TIA (Neurology 2008;70:841)....These new findings suggest that, for patients with stroke or TIA, we should consider other elements of the lipid profile, including triglycerides and non-HDL cholesterol; the latter encompasses all apolipoprotein-B–containing particles. Non-HDL-C should be considered the primary target of therapy in clinical practice and including these values in routine lab reports should be the standard (Mayo Clin Proc 2010;85:446-50)…efforts to use apo B should be put on hold. See below.
Combined hyperlipidemia: defined as increased LDL, decreased HDL, and increased triglyceride levels.
Major Cardiac risk Factors: M>45, F>55, HLD <35, current smoking, HTN, DM, FHx premature CAD (AMI/sudden death 1st Male relative <55 or 1st Female relative <65yo), homocystinemia.
Minor: Obese, sedentary lifestyle, incr Trig’s, Lp(a)-small dense LDL, passive smoking, depression, calcifications in the aortic arch. Anticardiolipin Ab’s, other (see Cardiology Chapter).
Pt Explanation of Cholesterol:
HDL= “Higher Degree of Living” as a protective “helmet” or “healthy chol”, removes cholesterol from the body by accepting cholesterol from the periphery and delivering it to the liver (reverse’s cholesterol transport).
<40 mg/dL = low HDL cholesterol. A major risk factor for heart disease.
40 to 59 mg/dL is better, the higher your HDL level, the better.
>60 mg/dL = optimal, considered protective against heart disease.
LDL= “Lower Degree of Living” as lethal / lousy cholesterol. Transports cholesterol from liver to all peripheral tissues.
A decrease of 6% give a decrease of 12% CAD risk.
<100 mg/dL = Optimal.
100-129 mg/dL = Near optimal / above optimal.
130-159 mg/dL = Borderline high.
160-189 mg/dL = High.
>190 mg/dL = Very high.
Triglyceride Level Category
<150 mg/dL = Normal.
150-199 mg/dL = Borderline high.
200-499 mg/dL = High.
>500 mg/dL = Very high. See Triglyceride |
Risk of Coronary Heart Disease and Total Cholesterol: (Arch Int Med 2003;163:1966-72).
<200 mg/dl (5.2 mmol/L): 31% lifetime (at age 40-80yo), 3% 10yr cumulative risk if male, 1% if female.
200-239 mg/dL (5.2-6.19 mmol/L): 43% lifetime, 5% 10yr risk if male, 2% if female.
>240 (6.2 mmol/L): 57% lifetime, 12% 10yr risk if male, 5% if female.
Other info: Only trig’s and calculated LDL require a pt to be fasting for 12hr. Elevated LDL, Trig, decr HDL, are all independent cardiac risk factors. 35% CAD still occurs in those with Chol <200, thus consider tx even if <200 but have risk factors. 70% of diabetics have incr chol & trig. Tx gives a 30% decr mortality, tx all DM with statin first. Low chol does not protect against smoking related CAD (JAMA 1999;282:2149). C-reactive protein better than LDL cholesterol in predicting first cardiovascular events (NEJM 2002;347:1557-1565,1615-1616). Total chol has a seasonal variation of 4-5 mg/dL (0.1-0.14 mmol/L), with a peak in the winter mo’s and greater amplitude in women and those with hypercholesterolemia (Arch Int Med 2004;164:863-70) (related to fat intake, physical activity, mood, light exposure). Analysis from the Women's Health Study confirms that high levels of non-HDL-C > total cholesterol > HDL-C, and LDL-C are significantly associated with an increased risk for ischemic stroke, even in women who are otherwise healthy (Neurology. 2007;68:556-562). An analysis of two studies (Treating to New Targets [TNT] and Incremental Decrease in End Points through Aggressive Lipid Lowering [IDEAL] trials) that contributed to reducing LDL-cholesterol levels to lower and lower targets has shown that on-treatment levels of non–HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcomes than levels of LDL cholesterol (Circulation. 2008;117:3002-3009)...."Demonstrating the superiority of non-HDL cholesterol or apoB over LDL cholesterol as a cardiovascular risk predictor during statin treatment"......"When you use LDL cholesterol, you don't take into account the intermediate-density particles, things that have more triglycerides in them but still have a lot of cholesterol"....Compared with individual lipoprotein cholesterol values, the total/HDL cholesterol ratio, and the apolipoprotein B/A-I ratio in particular, were each more closely associated with cardiovascular outcome. This was true when a composite endpoint of coronary death, nonfatal myocardial infarction, resuscitation after cardiac arrest, and fatal or nonfatal stroke, or an endpoint of myocardial infarction alone, was used.
Lipid Tx Goals: To convert mg/dL to mmol/L, you multiply by 0.02586. See Tx Strategies |
Risk factors: cigarette smoking, HTN (BP >140/90 mm Hg, even if treated), low HDL, FHx of premature CHD, and age (men >45 years, women >55 years).
Risk Calculator: http://hin.nhlbi.nih.gov/atpiii/calculator.asp
Lower risk:
Without CAD & <2 risk factors = people with zero or one risk factor.
LDL goal <160 mg/dL, TC <240.
Moderately risk:
Without CAD & >2 risk factors and a ten-year risk of CHD between 10-20% (www.nhlbi.nih.gov/guidlines/chol).
LDL goal is <130 (3.35 mmol / L)...but you're encouraged to get pt’s down to <100 mg/dL (2.6 mmol/L).
High risk:
+ h/o CAD or CAD risk equivalents (diabetes, AAA, PVD) or >20% 10-years risk equivalents of CAD for coronary events (www.nhlbi.nih.gov/guidlines/chol).
LDL goal is <100 (2.6 mmol/L)...with encouragement to go to <70 mg/dL. TC (total chol) <200 (2.25 mmol / L). HDL >40 mg/dL. Add 1mg folate qd. Non-HDL Chol <130 mg/dL if TGs >200 mg/dL (Circulation 2006;113:2363-72). Pharmacologic therapy is recommended for all people at high risk. Even if age >65yo, so long as in good health (Clinical Geriatrics 2002;10:9).
Very high risk:
Heart disease plus multiple or poorly controlled risk factors.
LDL goal of <70 mg/dL (1.80 mmol / L). For people at very high risk of MI or death. Very high risk individuals are those with CAD + diabetes, persistent cigarette smoking, poorly controlled HTN, or multiple risk factors of the metabolic syndrome (high trig, low HDL, obesity), and those who recently had an AMI (Circulation 2004;110:227-39). There is no high-quality clinical evidence supporting the recommended tx target of ultralow LDL levels (<70 mg/dL) in high-risk pt’s (Ann Intern Med 2006; 145:520-530). Dropping LDL from 100 to 70 in 100 pt’s for 5 years prevents 1.5 events. Statins used in pt’s with extremely low LDL cholesterol levels (<40 mg/dL) and those without documented CAD are safe and may lead to improved survival (Circulation 2007; 116:613-618). Researchers suggest, however, that treating to LDL-cholesterol levels to between 40 and 60 mg/dL confers even more benefit than <70 mg/dL (Circulation 2008;118:672-677)..... proponents of measuring apoB, as it is a surrogate of the number of atherogenic particles, including VLDL and LDL, rather than LDL, which is a surrogate for the cholesterol concentration of the LDL particle. HDL levels were not associated with residual cardiovascular risk in patients treated with potent statin therapy (rosuvastatin 20 mg daily) (Lancet 2010;376:333).....suggest that HDL levels do not predict cardiovascular events in patients who attain very low LDL levels (median on-treatment LDL level was 54 mg/dL = 1.4 mmol/L) with potent statin therapy for primary prevention.....At 2 years, the composite event rate was 44% lower (P<0.0001) in the rosuvastatin group than in the placebo group.
A simple risk-based approach (treating patients who have 5%–15% CAD risk with daily 40-mg simvastatin and patients who have >15% risk with daily 40-mg atorvastatin, with no dose adjustments) might be better than titrating to a specific cholesterol level ("treat-to-target" strategy based on NCEP guidelines) (Ann Intern Med 2010;152:69).....The analysis showed that about 70% of patients would receive similar treatment regardless of strategy, 14% would receive more-aggressive treatment with the risk-based approach, and 17% would receive more-aggressive treatment with the intensive treat-to-target approach.....However, more CAD events would be prevented with the risk-based approach than the intensive treat-to-target approach (62 vs. 15 per 1000 treated patients).
American Heart Association Guidelines for Women:
1) Initiate statin tx for high-risk women regardless of their LDL levels. Strongly consider if low risk women with LDL >190 mg/dL.
2) Maintain an optimal level HDL >50 mg/dL.
3) Initiate niacin or fibrate therapy for low HDL or elevated non-HDL chol levels in high-risk women.
*** High-risk women are those with a 20% risk of developing cardiac disease in 10 years. Intermediate-risk women have a 10-20% risk. Low-risk women have a <10%. (AACE 14th Annual Meeting and Clinical Congress: General Session. Presented May 19, 2005)
Stroke Prevention: In a large meta-analysis, non-HDL cholesterol was associated with risk for ischemic but not hemorrhagic stroke; levels of other lipid markers, including triglycerides, HDL, and apolipoproteins were not associated with stroke risk (JAMA 2009;302:1993)......These findings appear to validate the approach to stroke prevention of using statin therapy targeted at LDL levels, and they also help allay the concern that low LDL levels might be associated with increased risk for cerebral hemorrhage......They do not support use of niacin, an HDL-raising treatment, for stroke prevention......However, in stroke patients at high risk for cardiac disease (e.g., those with carotid disease), HDL-directed therapies may help reduce cardiac risk.
Intensive Therapy (Low LDL’s): Current recommendations are stillto begin statin therapy at a lower dose and titrate upward, as on average, doubling the dose only reduces LDL levels by an additional 6%.....Neither absolute LDL level nor percentage decrease in LDL appears to be linked with the risk of myopathy or rhabdomyolysis in statin treated pt’s (The safety of aggressive statin therapy. Mayo Clin Proc 2006;81:1225-31). Pt's hospitalized for an acute coronary syndrome who were treated with an intensive (80mg, high-dose atorvastatin for a median LDL <62 mg/dL), compared with a moderate (40 mg pravastatin), lipid-lowering statin, showed lower risk of major cardiac events or death from any cause (16% reduction in the hazard ratio) (NEJM 2004;350). Intensive lipid-lowering therapy (LDL goal <80 mg/dL) with atorvastatin (80mg) is more effective than conventional therapy (LDL average was 109) with pravastatin (40mg) at slowing the progression of coronary atherosclerosis (JAMA 2004;291:1071-1080,1132-1134), at 18-mo’s, 2.7% of pt’s in the pravastatin group had experienced atherosclerosis progression compared with none of the pt’s in the atorvastatin group as measured by intravascular U/S, according to the results of the Reversal of Atherosclerosis with Lipitor (REVERSAL) study (also had a 36.4% reduction in CRP compared to 5.2%). More aggressive lowering of LDL (<70 mg/dL) benefits pt's with stable coronary heart disease in terms of risk for stroke and MI (NEJM 2005;352:1425-35) (overall mortality did not significantly). In pt's with prior AMI, high-dose atorvastatin (80mg) was better than standard-dose simvastatin (20mg) as had an additional 20% reduction in stroke and fewer major cardiovascular events (HR, 0.87) without increased morbidity (The IDEAL study. JAMA. 2005;294:2292-2294) (average LDL 81 Vs 104 mg/dL)…..low dose statins prevent heart attacks and cardiac death, but one additional cardiovascular event is prevented for every 15 high-risk pt's treated for 5 years with high-dose statins. A retrospective analysis of 1800 pt's suggests that intensive lipid-lowering therapy to achieve very low LDL levels is safe and effective (lower-LDL pt's had fewer cardiac events with no difference in liver, muscle, or retinal abnormalities) (J Am Coll Cardiol 2005;46:1411-6) (30% had and LDL 40–60 mg/dL, and 11% had levels of <40 mg/dL). Even pt's with an ACS who have an LDL cholesterol level <80 mg/dL who are not on a statin at hospital admission benefit from initiating statin therapy at discharge based on a retrospective study with 155 pt's (Am J Cardiol 2005;96:1491-1493) (had a lower incidence of death, reinfarction, or stroke at six mo’s (29% vs 9.5%; p = 0.005) compared to those pt’s who were not discharged on statin therapy. In elderly pt's >65yo, a statistically significant decrease in positive affect (happiness, contentment, energy) emerged in the simvastatin group (if Tchol <148 mg/dL) compared with the placebo group (J Am Geriatr Soc 2006;54:70-6).....aggressive cholesterol lowering might result in subtle affective changes in older adults. Rosuvastatin (40 mg) can regress the atherosclerosis burden (IVUS-documented regression) when get LDL 60.8 ± 20.0 mg/dL (JAMA. 2006 Posted online March 13, 2006) (effect on hard cardiovascular end points pending). Intensive statin therapy (LDL <70 mg/dL) lowers the risk of heart failure hospitalizations by 45% (1.6% Vs 3.1%) in pt's after acute coronary syndrome more than moderate statin therapy does (J Am Coll Cardiol 2006;47:2326-2331). A meta-analysis of 12 RCT's of aggressive lipid lowering found that the relative risks for major adverse coronary events were reduced similarly, by 21% in diabetic pt’s and by 23% in nondiabetic pt’s (BMJ 2006;332:1115-8)....unfortunatley 70% of adverse cardiovascular events will still occur. A meta-analysis of these four studies showed high-dose statins provide a 16% odds reduction for coronary death or heart attack or any cardiovascular event (J Am Coll Cardiol 2006;48:438-45) (NNT to prevent one cardiovascular event was 29 pt’s for 2 yrs)….a trend toward decreased cardiovascular death.
5 Key Lipid Lowering Strategies:
The goal is to treat atherogenic dyslipidemia (ultimately prevent CAD and CVA’s), not simply to treat excursions from normative lipid subfraction levels.
#1. Exclude secondary causes (DM, thyroid, nephrotic, liver dz), see below.
#2. Therapeutic Lifestyle Changes: Links: Dietary | Functional Foods | Children and Elderly pt’s | The cumulative effect of multiple therapeutic lifestyle changes may yield up to a 30% reduction in LDL-C and result in a significant increase in HDL-C (J CMS 2006;1;5:308-312). This included engaging dietitians/ nutritionists and diabetes educators in combination with promoting physical exercise.
Exercise: frequency more important than intensity for increasing HDL (Am J Card 2001;87:942). The amount of exercise (total time) might be more important than the intensity of exercise in favorably influencing lipoprotein measures among overweight, sedentary adults (NEJM 2002;347:1483-92).
#3. If incr LDL>20-25% & Trig <500 or secondary prevention start with a Statin. Statin therapy is associated with regression of coronary atherosclerosis when LDL is reduced to <87.5 mg/dL (2.3mmol/L) combined with an HDL increase of >7.5% (JAMA 2007;297:499-508). Repeat lipids and check LFT’s 0, 6, 12wks, then q6-12mo, if profile not improved (<15% decr LDL or incr HDL) --> change drugs or if HDL still <35 and need a second agent--> add Niacin.
If HDL >35--> add bile sequestrant first, then niacin PRN as 3rd line. Aim for an HDL of 45mg/dL in men, 55 if women. Current guidelines for the prevention of coronary heart disease focus on lowering LDL-C as the primary target of lipid-modifying therapy (Low HDL-C: A secondary target of dyslipidemia therapy.Am J Med 2005;118:1067-1077).....statins are recommended as first-line drug therapy because of their LDL-C lowering efficacy.
#4. If incr LDL & Trig 200-400. Start a statin, may need to add nicotinic acid/ fibric acid. Or Nicotinic acid--> statin/ fibric acid.
#5. Primary Prevention (35-75yo) --> Niacin or Bile Acid sequestrant, Statin.
• Incr LDL, nl/dec HDL and nl TG: First choice: statin. Other choices: ezetimibe, nicotinic acid, bile acid resins.
• Incr LDL, dec HDL and inc TG: First choice: nicotinic acid. Other choices: Fibrates (but may raise LDL). Statin with fibrate (higher risk of myopathy). Ezetimibe.
• Incr TG, decr HDL, nl LDL: First choice: nicotinic acid or fibrate (remember: may increase LDL)
• Nl LDL, Nl HDL and incr TG: Need for treatment not well established unless TG > 500 mg/dL (risk of pancreatitis). Meta-analyses indicate TG are an independent risk factor for CHD. First choice: fibrates. Other choice: nicotinic acid.
Important Contraindications:
Statins: Active or chronic liver disease.
Ezetimibe: Active or chronic liver disease.
Bile acid resins: Dysbetalipoproteinemia or TG > 400 mg/dL
Fibrates: Severe kidney or liver disease.
Nicotinic acid: Chronic liver disease or Severe gout.
Compliance: Many pt's with high cholesterol don't take their statin medication as prescribed (Pharm J 2004:272:23-26). The risk of dying from a non-cardiovascular cause was nearly 4X higher in the non-compliant group. Compliance-enhancing initiatives such as regular cholesterol monitoring, is a statistically significant predictor of pt compliance. Simple ways of informing patients about their cardiovascular risk (concept of "cardiovascular age" = the gap between their actual age and "cardiovascular age") via sharing a personalized coronary risk profile with patients can make them more likely to adhere to medical advice and reach lipid goals, a study suggests (Arch Intern Med. 2007;167:2296-2303)……(http://www.myhealthcheckup.com/CVDAssessement/CVDTest.aspx).....This information may also assist physicians in treatment selection while improving pt adherence.
Elderly men and women who have higher LDL cholesterol levels are associated with decreasing total mortality risk in women and decreased risk of fatal heart failure in both genders (J Am Geriatr Soc 2005;53:2159-2164). Low total serum chol (<189 mg/dL without taking chol meds) is associated with incr mortality in the elderly and in risk of suicide (Epidemiology 2001;12:168) (J Am Geri Soc 2003;51:991-6), may possibly be a warning sign of occult dz or rapidly declining health. HDL cholesterol level is inversely associated to the risk of thromboembolic stroke in elderly men (Am J Epidemiol 2004;160:150-157), the risk declined consistently with increasing levels of HDL with desirable total cholesterol concentrations. Elevated level of Lp(a) lipoprotein is an independent predictor of stroke and of death from vascular disease or from any cause in elderly men, but not in elderly women (NEJM 2003;349:2108-15). Statin therapy is associated with improved clinical outcomes, reducing 1yr all-cause mortality and death/ hospitalization of frail elderly (J Am Ger Soc 2002;50:1389-95). Although statins lower mortality in AMI pt’s between 65 and 80 years old, they may not be as effective in older pt’s (J Am Geriatr Soc 2006;54:421-430).....pt's who had LDL cholesterol levels above 130 mg/dL were most likely to benefit from statin therapy, and pt’s who had LDL cholesterol levels below 100 mg/dL were least likely to benefit. Very hostile older white men were more likely than their less hostile peers to cope poorly with stress and have lower HDL cholesterol levels (data from 716 men with a mean age of 65yo) (American Psychological Association 115th Annual Meeting. August 17-20, 2007).
In general, save meds for when a genetic dyslipidemia is suspected...such as kids with an LDL over 190 mg/dL (Prescriber's Letter 2012;19:1)....If meds are needed, start with a low-dose statin, most are approved for kids as young as 10...and pravastatin for as young as 8. ...Statins are contraindicated during pregnancy because of possible harm to the fetus. Screening on the basis of family history missed many (29%) children with hyperlipidemia (Pediatrics 2010 Aug; 126:260). BMI may be a poor marker for hypercholesterolemia in children and adolescents according to the results of a cross-sectional analysis (Arch Pediatr Adolesc Med. 2009;163:716–722)...."ecommendations for targeted screening of obese children and adolescents may require further consideration." Roughly 20% of U.S. youths aged 12 to 19 have at least one abnormal lipid level, with overweight and obese teens being most at risk,according to an analysis of NHANES data (MMWR January 22, 2010 / 59(02);29-33).....abnormal lipid levels were noted in 14% of normal-weight, 22% of overweight, and 43% of obese adolescents. Children who are overweight run a greater risk of having lipid profiles that signal a high risk for cardiovascular disease, and risk gets progressively higher with age (Pediatric Academic Societies (PAS) 2010 Annual Meeting: Platform session 4140.3. Presented May 4, 2010).....a precipitous rise in overweight children beginning at about 4 years of age, levels were maintained, producing "much, much higher values" in adolescence, levels exceeded 200 mg/dL in overweight children by the time they were about 8 years of age, and consistently increased with age, hitting 250 mg/dL by age 16.
AAP Lipid Screening in Childhood Recommendations from the AAP:
Cholesterol screening of high-risk children should be done before age 10 and fasting lipids should be re-checked every three to five years (Pediatrics 2008;122:198).
1) Autopsy data indicate that the atherosclerotic process begins in childhood and that elevated cholesterol levels in childhood are associated with increased risk for cardiovascular disease (CVD) in adulthood;
2) Lipid and lipoprotein levels rise rapidly early in life and stabilize by age 5 to levels similar to those of adolescents; and
3) Currently, 35% to 45% of children are screened because of positive family history of CVD.
-- Screening is recommended every 3 to 5 years, optimally beginning at age 2 years and certainly no later than age 10 for children with positive family histories of dyslipidemia or premature CVD (i.e., CVD diagnosed before age 55 for men and 65 for women); unknown family history; or other CVD risk factors (overweight or obesity, hypertension, cigarette smoking, or diabetes).
-- A fasting lipid profile is the recommended screening approach, and interpretation should be based on reference charts provided in the report.
-- Weight management is the primary treatment strategy for overweight or obese children with high triglyceride levels or low high-density lipoprotein levels.
-- For patients 8 years and older with an LDL concentration of 190 mg/dL (or 160 mg/dL with a family history of early heart disease or 2 additional risk factors present or 130 mg/dL if diabetes mellitus is present), pharmacologic intervention should be considered. The initial goal is to lower LDL concentration to <160 mg/dL. However, targets as low as 130 mg/dL or even 110 mg/dL may be warranted when there is a strong family history of CVD, especially with other risk factors including obesity, diabetes mellitus, the metabolic syndrome and other higher-risk situations.
-- No specific drugs were recommended, but the committee wrote that statins have been tested in children and adolescents and appear to be well tolerated. The FDA has approved pravastatin (Pravachol) for familial hypercholesterolemia in children ages eight or older.
-- Cholesterol-absorption inhibitors (currently ezetimibe [Zetia]) is the only approved drug in this class) have not been extensively studied in children.
-- Fibrates should be used "cautiously and under the supervision of a pediatric lipid specialist."
-- In pediatric trials, niacin was associated with flushing in 76% of children and elevation of liver enzymes in 26% of children studied. As a result, the committee concluded that niacin could not be recommended for routine use in treatment of pediatric dyslipidemia.
-- Bile acid-binding resins are also a poor choice because gastrointestinal complaints limit their use for young patients.
-- For children who have either high triglycerides or low HDLs, weight management, including diet and nutrition counselling as well as an exercise program, should be the primary treatment.
-- The academy recommended the use of reduced-fat milk for children ages 12 months to two years who are overweight or obese or who have a positive family history of premature heart disease. The academy defined premature heart disease as affecting men 55 or younger and women 65 or younger.
Pediatric dyslipidemia:
Total cholesterol (TC) >200 mg/dL (5.18 mmol/L).
LDL-C >130 mg/dL (3.36 mmol/L).
HDL-C <40 to 45 mg/dL (1.0 mmol/L).
Triglycerides >150 mg/dL (1.7 mmol/L) in adolescents and >130 mg/dL (1.47 mmol/L) in younger children. If elevated triglycerides, a diet that is low in carbohydrate intake is recommended, and in patients with hyperchylomicronemia related to rare genetic disorders such as lipoprotein lipase deficiency (Frederickson's Type I), fat restriction may be necessary.
Nonpharmacologic Therapy: lifestyle modification such as dietary interventions and increased activity. Always consider at least a six-month trial before starting pharmacologic therapy.
Activity: daily vigorous activity decreases the risk of CVD and improves fasting lipid profiles. Recommend 30 to 60 minutes of exercise, 4 to 6 times a week. An adequate degree of exertion is indicated by breathlessness, fatigue and sweating.
Diet: a low-saturated-fat, low-cholesterol diet that has the appropriate number of calories to support growth and development (based upon the age, sex, and activity level). Full of fruit and vegetables, whole grains, low-fat and nonfat dairy products, beans, fish, and lean meat. Saturated fat to <10% and total fat to <30% of the total calories consumed, and the daily intake of dietary cholesterol to <300 mg/day. If LDL-C >130 mg/dL (3.36 mmol/L), will need a reduction of saturated fat to <7% of total calories and cholesterol to less than 200 mg/day. If severe dyslipidemia (LDL-C >190 mg/dL [4.9 mmol/L]), diet modification alone is rarely sufficient to reach target levels and pharmacologic therapy should be considered.
Failure of nonpharmacologic therapy:
A. LDL-C >190 mg/dL (4.9 mmol/L) without other CVD risk factors. OR
B. LDL-C >160 mg/dL (4.1 mmol/L) but <190 mg/dL (4.9 mmol/L) and one of the following 3 conditions:
1) FHx of premature CVD.
2) two or more other CVD risk factors after vigorous attempts to control CVD risk factors (overweight, hypertension, insulin resistance, or smoke exposure).
3) a primary disease associated with a moderate or mild increased risk of CVD such as Kawasaki's and Diabetes. OR
C. LDL-C >130 mg/dL and the pt has moderate risk underlying disease, such as heterozygous familial hypercholesterolemia, or type II diabetes mellitus. OR
D. LDL-C >100 mg/dL and the pt has high risk underlying disease, such as homozygous FH, or diabetes mellitus type I.
Starting Rx: initiated at the lowest dose, usually at bedtime because most LDL-C synthesis occurs during the night.
Pearls: Repeat lipids and ALT 6-8 weeks after you adjust or initiate dose and then q6mo's with growth monitoring if all is stable. If there are lab abnormalities, the drug is stopped for 2 weeks and the lab testing is repeated. When the abnormalities resolve, the drug may be restarted with close monitoring. Most will Rx a statin drug, other options include fibric acid derivatives, bile acid sequestrants, nicotinic acid, and cholesterol absorption inhibitors (ezetimibe). Fasting blood samples were obtained and LDL cholesterol levels were available for 2724 children, of which, only 26 adolescents (0.8%) potentially qualified for pharmacologic treatment per the AAP guidelines (Circulation 2009 Feb 16;e-pub ahead of print)....11 had LDL concentrations >190 mg/dL, and 15 had LDL concentrations >160 mg/dL plus at least one risk factor (obesity, diabetes, hypertension, cigarette smoking, or a positive family history of premature cardiovascular disease)......treatment is recommended only if abnormal values persist after diet and weight management.
Targeted values of LDL-C:
Minimal risks: <130 mg/dL (3.35 mmol/L), Optimal is <110 mg/dL (2.85 mmol/L).
High risks due to co-existing disease: <100 mg/dL.
Cholesterol testing of toddlers or young children proved an effective screening method for familial hypercholesterolemia according to a meta-analysis (BMJ 2007;doi:10.1136/bmj.39300.616076.55)....It identified about 96% of affected parents and provided the opportunity to prevent the disorder in two generations at once....15 months is a good age at which to test a child for cholesterol, although tx should wait until adulthood. All should be screened if have a parent with a total chol >240mg/dL or if parent/grandparent with premature CAD/CVA. Lovastatin, simvastatin (Zocor), pravastatin, and atorvastatin (Lipitor) are FDA approved for pediatric use as of 8/07. The USPSTF states it can make no recommendations for or against routinely screening for lipid disorders in children, adolescents based on currently available evidence (Pediatrics. 2007;102:e189-e219)....screening per family history could miss as many as 60% of dyslipidemia cases. Early long-term statin therapy can help prevent arterial damage in familial hypercholesterolemia according to a study of children as young as age eight (Circulation 2007;116:664-668).
If child is >170 mg/dL need diet and exercise with re-check in 2yrs. In child age 2-19yo aim for a TC <170mg/dL, LDL <110 mg/dL, Trig <120 and HDL >40 mg/dL. Daily pravastatin (20-40 mg) appears safe in children with LDL >155 mg/dL, no changes in height and weight, liver function tests, pubertal status, and levels of various hormones compared to placebo (Efficacy and safety of statin therapy in children with familial hypercholesterolemia: A randomized controlled trial. JAMA 2004;292:331-7). Starting statin therapy early in children with familial hypercholesterolemia appears to delay the progression of carotid intima-media thickness (IMT) (Circulation 2007;116;Aug 08).
The American Heart Association (AHA) scientific statement highlighting evidence supporting drug therapy for the tx of high-risk lipid abnormalities in children and adolescents such as familial hypercholesterolemia, diabetes, or a family history of cardiovascular disease (Circulation. 2007;115:000-000, online March 22, 2007).....with lipid abnormalities associated with childhood obesity, weight loss remains the cornerstone of therapy, but in certain individuals, drug therapy may be required.
Other highlights from the AHA statement include: Obesity and overweight, in addition to family history, should trigger cholesterol screening in children and adolescents. Obese and overweight children and adolescents should be screened for other aspects of the metabolic syndrome (BP, elevated triglycerides, low HDL, and high fasting glucose levels). Lifestyle modification should be implemented for most children, but statins, for children who meet the criteria, are the first-line lipid-lowering therapy if there are no contraindications. Based solely on LDL levels, children eligible for drug therapy include those with LDL levels of 190 mg/dL or greater or LDL levels of 160 mg/dL or greater with a positive family history of premature cardiovascular disease or at least 2 other significant cardiovascular risk factors. Risk factors to consider include male sex, other lipid abnormalities, overweight and obesity, and the presence of the metabolic syndrome, hypertension, HIV infection, or systemic lupus erythematosus. The minimal LDL tx goal should be a reduction to levels < 130 mg/dL. Ideally, levels should fall below 110 mg/dL. Bile acid-binding resins were previously recommended as first-line therapy for the tx of hyperlipidemia in children, in part because they are not systemically absorbed. However, these medications are poorly tolerated and may increase triglyceride levels.
Dosing Recommendations for HMG CoA Reductase Inhibitors in Children: Approved U.S. Daily Dosing
Atorvastatin (Lipitor): 10 to 17 years old. 10 mg (starting). 20 mg (maximum).
Fluvastatin (Lescol, Lescol XL): 10 to 16 years old. 20 mg (starting). 80 mg (maximum).
Lovastatin (Mevacor): 10 to 17 years old. 10 to 40 mg (range). 40 mg (maximum).
Pravastatin (Pravachol): 8 to 13 years old. 20 mg (starting). 20 mg (maximum).
14 to 18 years old: 40 mg (starting). 40 mg (maximum).
Rosuvastatin (Crestor): 10 to 17 years old. 5 mg to 20 mg (starting). 20 mg (maximum).
Simvastatin (Zocor): 10 to 17 years old. 10 mg (starting). 40 mg (maximum).
High levels of triglycerides may also warrant pharmacological treatment. Levels at which to treat high triglycerides in children haven't been established. However, drug therapy can be considered in children with persistent fasting triglyceride levels greater than 350 mg/dL (4 mmol/L) or random triglyceride levels greater than 700 mg/dL (7.9 mmol/L) to decrease the risk of pancreatitis.17 In these children, fibric acid derivatives (gemfibrozil [Lopid] or fenofibrate [Tricor]) or niacin can be used for their triglyceride-lowering effects. However, niacin may be poorly tolerated due to flushing. In addition, some clinicians recommend fish oil capsules to reduce high serum triglycerides. (Pharmacist's Letter/Prescriber's Letter 2008;24(6):240612)
Age & Sex-specific Lipoprotein Threshold Concentrations for Adolescents: Rreflect the natural fluctuations in cholesterol levels that occur with growth and maturation (Circulation. Posted online August 28, 2006). The current NCEP definitions of hyperlipidemia in children are limited because they do not adjust for age and sex, they use cutoff points that may not have clinical significance, and they were developed when children's lipid profiles were different from today's children. The current study's results suggest that total cholesterol levels > 5.5 mmol/L are abnormally high in adolescents. Cutoff points for abnormally high lipid values do not necessarily rise with age in adolescents.
Links: Diet & wt loss | Triglyceride | Functional Foods (Stanols, Garlic, Psyllium etc) | Omega-3 fatty acids (Fish oil) |
A 2-6mo trial of diet therapy / lifestyle modification (wt loss/ exercise) is always reasonable for most patients. Expect decr 5-10% on average, can decr 35% if “diet sensitive” and compliant. A diet low in saturated fat, but rich in monounsaturated fat (Mediterranean Diet) improves endothelial function (Ann Intern Med 2001;134:1115). Multiple small meals (5-6X/d) gives a 5% reduction in T-chol & LDL by possibly stimulating metabolism (BJM 2001;323:1286). Cholesterol that is oxidized in foods by frying or other high-heat cooking methods may be substantially worse for the arteries according to results of an animal study (Chen Z-Y, et al "Oxidized cholesterol is more hypercholesterolemic and atherogenic than nonoxidized cholesterol in hamster" ACS 2009; AGFD 23).....In hamsters, an otherwise identical diet produced 12% to 22% higher total blood lipid levels if the cholesterol was oxidized.
Dietary Factors in Cholesterol Reduction:
Factor: Modification Required: --> Decr in LDL-C.
Cholesterol intake: <200 mg/d intake--> 5%.
Weight reduction: 10# (5kg) loss--> 5 %.
Soluble fiber intake: 5-10 g/d--> 5%.
Soy protein: 25 g/d--> 5%.
Plant Sterols: 1-3 g/d--> 5%.
Saturated Fat + trans- Fatty Acid intake: <7% of total daily cals--> 10%.
Total Reduction- All factors (if additive) --> ~35% (Am J Clin Nutr 2000;71:401-02) If fail to reach goal, consider niacin or bile acid sequester. If not improved with age >45yo male or >55yo female and has one additional risk factor for CAD proceed to a statin. A traditional low-saturated-fat diet (low-saturated-fat dairy and whole-grain diet) has only modest cholesterol-lowering effects, as this diet gives a 8% decrease in LDL, adding lovastatin 20 mg/d gives a 31% decrease in LDL. But a very low-fat diet based on the National Cholesterol Education Program Step II diet plus plant sterols (in enriched margarine), soy protein, viscous fiber (milled whole-wheat cereals such as oats, barley, psyllium, eggplant, and okra), and almonds gave a 29% decrease in LDL (Effects of a dietary portfolio of cholesterol-lowering foods Vs lovastatin on serum lipids and C-reactive protein. JAMA 2003;290:502-10). Reductions in CRP were 10%, 33.3% and 28.2% respectively. Viscous fibers increase bile acid losses, plant sterols reduce cholesterol absorption, and soy proteins reduce hepatic cholesterol synthesis and increase LDL receptor messenger RNA and so potentially increase uptake of cholesterol. Adding walnuts to a low-fat diet improves lipid profile for pt's with type 2 diabetes (Diabetes Care. 2004;27:2777-2783) (a-linolenic acid [ALA], a polyunsaturated fatty acid, 30g/d gave a 10% reduction in LDL with an incr in HDL).
National Cholesterol Education Program (NCEP) Step 1 Diet:
Lowers Tchol -10%, LDL -12%, HDL -1.5% and Trig -8% (Am J Clin Nutr 1999;69:632-46).
Saturated fat (and trans-esterified fatty acids) <30% of total calories.
Polyunsaturated fat up to 10% of total calories.
Monounsaturated (olive > peanut > canola oil all decr LDL) fat up to 20% of total calories.
Total fat 25-35% of total calories.
Carbohydrates (predominantly complex) 50-60% of total calories.
Fiber 20-30 g/d.
Protein 15% of total calories.
Cholesterol <300 mg/dL.
Consider plant stanols/sterols (2 g/d).
Total calories aimed solely to achieve/ maintain desired weight (BMI 21-25). Incr viscous (soluble) fiber to 10-25g/d.
Step 2 Diet: same as Step 1 except: decr sat fat to <7% and chol to <200mg/d (5.2 mmol/L) (JAMA 2001; 285:2486-97).
Lowers Tchol -17%, LDL -25%, HDL -15% and Trig -16% (J Fam Prac 2007;56:46-9).
Restricting total fat intake to <25% of calories doesn't work well as below a certain threshold, the body will manufacture its own saturated fat (AACE 16th Annual Meeting and Clinical Congress: General Session. Presented April 15, 2007)….A high carbohydrate diet raises triglyceride levels and fails to show any weight-loss advantage….The high-fat, Atkins-type diet is similarly ineffective… physicians should emphasize moderate diet and aerobic exercise for pt’s with combined hyperlipidemia.
Portfolio Diet: combines the fat intake of NCEP Step 2 diet with the cholesterolol-lowering of functional foods such as plant sterols, nuts, soluble fibers and soy protein. Lowers Tchol -22.3%, LDL -29.7%, HDL -6.5% and Trig -9.3% (J Fam Prac 2007;56:46-9).
Mediterranean diet: Lowers Tchol -6%, LDL -11.4%, HDL -12.5% and Trig -0% (Am J Clin Nutr 2005;82:964-71).
Omega-3 fatty acids: Fish oil: 4g/d. Decr Trig (28%, mostly VLDL) & decr platelet aggregation, may incr LDL (7.5), incr HDL (2%). See ICU - Nutrition Module (Omega-3 fatty acids).
Cholesterol and Saturated Fat Content in Some Common Foods:
Food--> Cholesterol (mg/100 g) / Saturated Fat (g/100 g).
Eggs--> 500 / 3.
Organ meats (liver, kidney) --> >300 / 2.
Butter--> 230 / 50.
Shrimp, crab, lobster--> 110 / 1.
Cheese--> 110 / 21.
Meat (beef, pork, lamb) --> 90-100 / 513.
Poultry (no skin) --> 90 / 1.
Fish--> 70 / 1.
Ice cream (10% fat) --> 40 / 7.
Sherbet; frozen yogurt--> 4 / <1.
Milk, whole (3.5%)--> 14 / 2.
Milk, skim --> 2 / 0.
Cottage cheese--> 6 / <1.
Margarine, soft--> 0 / 16.
Vegetable oil--> 0 / 13.
Coconut oil, cocoa butter--> 0 / 75.
• A study found that people who ate daily servings of cheese for six-week intervals had lower LDL cholesterol than when they ate a comparable amount of butter (Am J Clin Nutr 2011;online October 26).....The cheese-eaters also did not have higher LDL during the experiment than when the same subjects ate a normal diet......Researchers gave each person cheese or butter, both made from cows milk, equal to 13% of their daily energy consumption from fat.....cheese has a lot of calcium, which has been shown to increase the amount of fat excreted by the digestive tract.
Topics: Phytosterols | Soluable Fiber (Oats, Psyllium) | Other (Garlic, Soy, Gugulipid, RYR) | Dietary |
Nutriceuticals. Foods being advertised as "heart healthy" will continue to rise due to a FDA program implemented September 1, 2003. This program allows certain foods to make "qualified health claims" without the strict standards previously in place. Along with intensive lifestyle modification (exercise, smoking cessation, stress management) can reduce frequency angina by 90% in 1yr (The Ornish diet. JAMA 1998;280).
Plant Sterols & Stanols (Phytosterols): National guidelines recommend 2 g/day of phytosterols as an option for high cholesterol….this offers a modest reduction in LDL cholesterol (~15%). Works by competing with cholesterol for absorption. Neither is well absorbed, but both are believed to have beneficial effects on cholesterol levels. They prevent cholesterol from being incorporated into a fat micelle that’s needed for absorption. Benefits are seen at about 1.3 grams daily of sterol esters. The maximum effective dose is believed to be ~ 2 grams daily. A typical American diet provides ~ 0.25 g of plant sterol per day. If you are a strict vegetarian, you are likely to consume between 600 and 800mg of plant sterols/stanols. A stanol-enriched diet can lower LDL cholesterol levels 15.6% in pt’s already receiving optimal doses of statins (J Am Diet Assoc 2006;106:1564-1569). Plant sterols in foods and supplements come mainly from soybeans and pine tree oil. Stanols are hydrogenated sterols.
Supplements: FDA says that supplements or fortified foods that provide at least 400 mg BID can lower LDL about 5% and reduce cardiac risk. Centrum Cardio has 400 mg/tab and is to be taken BID. Bayer with Heart Advantage has 400 mg phytosterols plus 81 mg aspirin per pill, which is not enough phytosterols.
Plant Sterols: They exert their effect on total and LDL cholesterol levels, with little or no impact on HDL or triglycerides. Found in OTC “Take Control: and Minute Maid Premium Heart Wise Orange Juice, and supplements such as Cholox.
Take Control: A natural unsaturated sterols from soybean oil. Inhibits cholesterol absorption (dietary & biliary) as structurally similar and compete with micelle formation. No systemic effects. Can be enriched into margarine or mayonnaise: 2-3 servings/day--> decr LDL 12% alone, but 20% if on low cholesterol diet (decr total chol 13%). Cost $4-5/wk. Canola (rapeseed oil) has sitosterol, an ingredient from the mustard family of plants, but not the same a “rape oil” used in animal feed.
Found Naturally In: Fruits, Vegetables, Nuts (almonds, pecans), Seeds, Cereals, Legumes, Vegetable Oils (particularly Soybean Oil). Also available in higher quantities in commercially prepared table spreads and plant stanol ester dietary supplements. Plant sterols and stanols are thought to reduce the absorption of cholesterol by our intestine. Plant sterols, also known as "phytosterols", are natural substances found in wood pulp, leaves, nuts, vegetable oils, corn, rice, and some other plants. The most abundant plant sterol is beta-sitosterol, while others present in the diet include campesterol, stigmasterol, and brassicasterol.
SE: Minor side effects are mild GI discomfort including gas, diarrhea and constipation. May decr serum beta-carotene. Plant sterols get absorbed into arterial plaque, but the role they play, if any, in the atheromatous process remains unclear (J Am Coll Cardiol 2005;45:1794-1801), the finding raises questions about the benefits of foods high in plant sterols for cardiovascular health. Consuming a diet high in plant sterols (1.8 g/d x 3wks) reduces LDL and non-HDL cholesterol levels in both diabetics (26.8%) and nondiabetics (15%) (Am J Clin Nutr 2005;81:1351-1358).
Plant Stanols: exert their effect in a similar manner as sterols, by stopping absorption of cholesterol. The benefits of stanols are believed to be dose related, with significant benefits beginning at 3.4 grams daily. They seem to impact primarily total cholesterol VLDL, and LDL levels, with little impact on either HDL or triglycerides. Total cholesterol levels decrease by ~5%, while LDL levels decrease 8% to 10%. One study did indicate an increase in HDLs by about ~5%.8 Plant stanols are found in several foods such as Benecol.
Can get them in pill forms (Cholesterol Success by Twinlab or Cholestatin by KAL) or with “cholesterol lowering margarines”. Studies have shown sterols reduced LDL by 9% to 20% and total cholesterol levels ~5%. Plant sterols are found in products such as Minute Maid Premium Heart Wise orange juice and Take Control. 1.5 tablespoons of Benecol contains 120 kcal, 13.5 g fat, and 1.5 g saturated fat, whereas 1.5 tablespoons of Take Control contains 75 kcal, 9 g fat, and 1.5 g saturated fat. OTC brands include “Cholest-Off”, using 450mg TID. There is abundant evidence (41 trials) that consuming 2g/d of sterols & stanols lowers LDL by 10% (additive to diets & drug interventions) and long-term use with lower CHD risk by 12-20% in 5yrs (Mayo Clin Proc 2003;78:965-78) (J Nutr 2000;130:767-7).
One (Benacol Spread): hydrogenated pine tree wood pulp forming sitostanol, which inhibits absorption of dietary and biliary cholesterol. 3 times daily (3 pats) costs ~$25/mo. Calorically similar to other spreads, comes in “light” as well. Decr T-chol 17% & LDL 20%. Cost 5X regular margarine, same calories. (Mayo Clin 1999;74:1198-1206) (Am J Clin Nutr 1999;69).
Soluble Fibers: The use of soluble fibers such as oats has been shown to modestly reduce total cholesterol and LDL by acting to prevent cholesterol absorption.
Psyllium (Metamucil): Blond psyllium husks are a source of natural soluble fiber. Patients who consume 10-12 grams of blond psyllium per day can decrease total cholesterol by 3% to 14% and LDL by 5% to 10% (Meta-analysis of 8 controlled trials. Am J Clin Nutr 2000;71:472-9). 5 g psyllium TID with 1 glass of water + simvastatin 10 mg qd was a effective as simvastatin 20 mg qd for lowering LDL cholesterol (29%) and ApoB (Arch Intern Med. 2005;165:1161-11669)…..safe, effective, and well-tolerated add-on therapy (no effects on lowering triglycerides or Apo A1 or increasing HDL-C levels). Psyllium husks are a source of natural soluble fiber, it is often used as a bulk laxative in product. A meta-analysis of 8 RCT’s concluded that when used in conjunction with a low-fat diet, psyllium supplements significantly reduce total cholesterol of 4% (ranges of 3% to 14%) compared to placebo, 9% reduction in LDL with no changes in HDL or in triglycerides (Am J Clin Nutr 2000;71:472-9). ~10 grams/d divided into 2 or 3 doses appear equally as effective.
Oats & Barley: Three servings of oatmeal or Cheerios provide 3 grams/day of soluble fiber can lower LDL about 5%. Shown to modestly reduce total cholesterol and LDL by acting to prevent cholesterol absorption. The reduction of total cholesterol ranges are generally between zero and 18%. It may be difficult to get the required amount of oats in dietary intake.
• The soluble fiber beta-glucan (from oats, 5g) added to a fruit drink lowers serum concentrations of total and LDL cholesterol (-4.8% & -7.7%) (Am J Clin Nutr 2006;83:601-605). Beta-glucan binds bile acids or increases intestinal viscosity resulting in a decreased reabsorption of bile acids and increased fecal bile acid excretion. The routine use of soluble fibers (barley beta-glucan) may be indicated in the diets of adult patients with and without hypercholesterolemia according to a meta-analysis (Ann Fam Med. 2009;7:157-163)......The use of barley was associated with significant reduction in levels of total cholesterol (weighted mean difference, –13.38 mg/dL), LDL cholesterol (weighted mean difference, –10.02 mg/dL), and triglycerides (weighted mean difference, –11.83 mg/dL).....there did not appear to be any significant effect on HDL cholesterol levels.
Ensemble: made by Kellogg, has soluble fiber from oats and psyllium husks for cakes, pasta, cookies. Minute Maid Heart Wise orange juice no contains sterols.
Cholesterol Free Spreads:
Smart Balance Buttery Spread: made from palm, soybean, olive and cannola, calories are 100% fat, but can be used for cooking, baking and table use. No hydrogenated oil, no trans fatty acids and provides a favorable ratio of Omega-6 to Omega 3 fatty acids.
I Can't Believe It's Not Butter Spray: butter taste that comes in a pump spray bottle. Zero fat or calories per serving .....If you look at the spray can, it refers to a serving as .25 grams. If use 1.25 pumps as the FDA allows a product to call it's self fat free if the serving size has < 0.5grams of fat. It's complete and total deception that allows pure fat to be labeled "Fat-Free" as most will use 4-5 pumps (1+g of fat). It is however primarily made up of soybean oil which is relatively healthy.
Other (Less Well Proven) Agents:
Garlic powder (Lipo guard): 1200mg cap qd. Garlic is thought to inhibit cholesterol biosynthesis and is an antioxidant with Vit-C/selenium/germanium, fish alters VLDL metab. Both are additive and synergistic. A meta-analysis of 13 RCT’s showed a reduction of 4% to 6% in cholesterol level with garlic as compared to placebo (Ann Intern Med 2000;133:420-9). Garlic Oil does not lower cholesterol (JAMA 1998;279) (Arch Intern Med. 2007;167:346-353). See Garlic | as other beneficial qualities.
Whole Grain Barley Products: 0.75 g of soluble fiber per serving, such as flakes, grits, flour, meal, and barley meal FDA approval of a qualified health claim for foods containing whole grain barley that reflects their potential for reducing the risk for coronary heart disease. A meta-analysis reviewing the effect of whole-grain foods or diets on CHD has shown that whole-grain cereals can reduce CHD risk factors, with specific reductions in total- and LDL levels (absolute reduction = 7 mg/L) (Cochrane Database Syst Rev 2007; DOI: 10.1002/14651858.CD005051.pub2).
Nuts: many nuts contain "good" unsaturated fats, including peanuts, almonds, walnuts, pecans, hazelnuts and pistachios. A handful daily can lower LDL 5% to 10%. Cashews & macadamia nuts have too much saturated fat, and pecan pie and Payday bars don't count. Cholesterol levels declined with mean daily consumption of 2.4 ounces according to a pooled analysis of 25 trials with 583 participants in seven countries (Arch Intern Med 2010;170:821).....estimated mean reductions from baseline in total cholesterol (TC) level (–10.9 mg/dL), LDL-cholesterol level (–10.2 mg/dL), and TC/HDL-cholesterol ratio (–0.24). Triglyceride levels declined (–20.6 mg/dL) among people with baseline levels 150 mg/dL. No change was noted for HDL-cholesterol levels. This relation was seen for all nuts, including peanuts.......Importantly, the authors note that moderate consumption of nuts is not associated with weight gain.
• The consumption of nuts of nearly any type improves blood lipid levels, lowering total- and LDL-cholesterol levels, and improves important lipid ratios, according to the results of a meta-analysis (Arch Intern Med 2010;170:821-827)......Consuming 67 g of nuts per day, the mean daily consumption across the 25 studies, reduced total- and LDL-cholesterol levels 10.9 mg/dL and 10.2 mg/dL, respectively.
Soy (Glycine soja): 25g/d. Studies have shown decreases in LDL of 6-18% and 6-10% in total cholesterol when between 20-47 grams of soy are consumed daily in conjunction with a diet low in saturated fat and cholesterol (Prescriber's Letter 2003;19:191205) (no impact on HDL or triglycerides). Purified soy isoflavone supplements alone do not seem to decrease LDL cholesterol (Prescriber's Letter. 2008;15:9)….The FDA has approved labeling soy products for heart disease risk reduction when used in combination with a diet low in saturated fat and cholesterol. To be eligible for this labeling, soy products must provide at least 6.25 grams of soy protein per serving, which is 25% of the effective amount of 25 grams per day. SE: stomach pain, loose stools/ diarrhea. Soy-protein-containing isoflavones decreased total cholesterol, LDL cholesterol, and LDL particle number in postmenopausal women (Menopause. 2007;14:106-114) (20 g of soy protein, containing 160 mg of total isoflavones, in a powder to be mixed with beverages. It contained 63 mg total diadzein, 64 mg total genistein, and 34 mg total glycitein).