Question on a fashionable topic in recent years: dyslipidemia; I would answer it by rule out. The treatment for hypercholesterolemia is statins so we rule out answers 2 and 4. The statin in a patient with cardiovascular disease (such as an AMI) is a lifelong treatment (we discard 1) since it is not taken until LDL levels are normalized. Between 3 and 5, 5 is more complete as it includes treatment and control of other risk factors. Ruling out secondary dyslipidemia is easy with the patient's clinical history and a blood test with thyroid function.

Question on a fashionable topic in recent years: dyslipidemia; I would answer it by rule out. The treatment for hypercholesterolemia is statins so we [HIDDEN]. The statin in a patient with cardiovascular disease (such as an AMI) is a lifelong treatment [HIDDEN] since it is not taken until LDL levels are normalized. Between 3 and 5, [HIDDEN] as it includes treatment and control of other risk factors. [HIDDEN] is easy with the patient's clinical history and a blood test with thyroid function.

A 57-year-old patient had an acute myocardial infarction and has a blood test with cholesterol 312 mg/dl, LDL 241 mg/dl, HDL 29 and normal TG. He smoked 30 cig/day, was not obese, his blood pressure was 145/90 mm Hg and he did not have diabetes. When asked about family history, he mentioned that an uncle on his mother's side died suddenly at 53 years of age. Which answer do you agree with the most?

Treat with statins until cholesterol is normalized and recommend healthy lifestyle (diet, exercise and no smoking).

Rule out hypothyroidism or other systemic disease, recommend a healthy lifestyle and treat with fibrates to normalize cholesterol.

It is not necessary to rule out secondary dyslipidemia because it is infrequent. A family lipid profile should be performed.

Rule out secondary dyslipidemia, treat with resins (resincholestyramine) and fibrates and re-commend a healthy lifestyle. Prohibit alcohol.

Rule out secondary dyslipidemia, request a family study and treat with statins to maintain a good lipid profile. Control of other risk factors.

Hypercholesterolemia

Treatment Treatment recommendations have been based on four risk levels for heart disease. For each risk level, LDL cholesterol levels representing goals and thresholds for treatment and other action are made. The higher the risk category, the lower the cholesterol thresholds. For those at high risk, a combination of lifestyle modification and statins has been shown to decrease mortality. Lifestyle Lifestyle changes recommended for those with high cholesterol include: smoking cessation, limiting alcohol consumption, increasing physical activity, and maintaining a healthy weight. Overweight or obese individuals can lower blood cholesterol by losing weight – on average a kilogram of weight loss can reduce LDL cholesterol by 0.8 mg/dl. Diet Eating a diet with a high proportion of vegetables, fruit, dietary fibre, and low in fats results in a modest decrease in total cholesterol.

Statin

The National Institute for Health and Clinical Excellence (NICE) recommends statin treatment for adults with an estimated 10 year risk of developing cardiovascular disease that is greater than 10%. Guidelines by the American College of Cardiology and the American Heart Association recommend statin treatment for primary prevention of cardiovascular disease in adults with LDL cholesterol ≥ 190 mg/dL or those with diabetes, age 40–75 with LDL-C 70–190 mg/dl; or in those with a 10-year risk of developing heart attack or stroke of 7.5% or more. In this latter group, statin assignment was not automatic, but was recommended to occur only after a clinician-patient risk discussion with shared decision making where other risk factors and lifestyle are addressed, the potential for benefit from a statin is weighed against the potential for adverse effects or drug interactions and informed patient preference is elicited. Moreover, if a risk decision was uncertain, factors such as family history,

Hypertriglyceridemia.

Hypertriglyceridemia is a commonly encountered lipid abnormality frequently associated with other lipid and metabolic derangements. The National Cholesterol Education Program recommends obtaining a fasting lipid panel in adults over the age of 20. The discovery of hypertriglyceridemia should prompt an investigation for secondary causes such as high fat diet, excessive alcohol intake, certain medications, and medical conditions (eg, diabetes mellitus, hypothyroidism). In addition, patients should be evaluated for other components of the metabolic syndrome. These include abdominal obesity, insulin resistance, low high-density lipoprotein (HDL), high triglyceride, and hypertension. Hypertriglyceridemia is classified as primary hypertriglyceridemia when there are no secondary causes identified. Primary hypertriglyceridemia is the result of various genetic defects leading to disordered triglyceride metabolism. It is important to treat hypertriglyceridemia to prevent pancreatitis by reducing triglyceride levels to <500 mg/dL. Furthermore, lowering triglycerides while treating other dyslipidemias and components of the metabolic syndrome will reduce coronary events. However, it is controversial how much isolated hypertriglyceridemia correlates directly with coronary artery disease and further studies are needed to clarify whether treatment for this condition leads to meaningful clinical outcomes. Therapeutic lifestyle changes (TLC) are the first line of treatment for hypertriglyceridemia. These changes include a low saturated fat, carbohydrate-controlled diet, combined with alcohol reduction, smoking cessation, and regular aerobic exercise. High doses of omega-3 fatty acids from fish and fish oil supplements will lower triglyceride levels significantly. When patients do not reach their goals by TLC, drug therapy should be started. In cases of isolated hypertriglyceridemia, fibrates are initially considered. When elevated low-density lipoprotein levels accompany hypertriglyceridemia, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are preferred. In patients with low HDL levels and hypertriglyceridemia, extended release niacin can be considered. A combination of the medicines may be necessary in recalcitrant cases.

Hyperlipidemia

Screening frequency Adults 20 years and older should have the cholesterol checked every four to six years, and most screening guidelines recommends testing every 5 years. USPSTF recommends increased frequency for people with elevated risk of CHD, which may be determined using cardiovascular disease risk scores. Management Management of hyperlipidemia includes maintenance of a normal body weight, increased physical activity, and decreased consumption of refined carbohydrates and simple sugars. Prescription drugs may be used to treat some people having significant risk factors, such as cardiovascular disease, LDL cholesterol greater than 190 mg/dl or diabetes. Common medication therapy is a statin. HMG-CoA reductase inhibitors

[Diabetes and lipids].

Dyslipidemia is one of the major cardiovascular risk factors especially for patients with type 2 diabetes mellitus. As a feature of the metabolic syndrome insulin resistance is also associated with an atherogenic lipoprotein phenotype. In type 1 diabetes inadequate glycemic control results in an increase of plasma triglyceride levels. The treatment of diabetic dyslipidemia is based on an improvement of glycemic control, in type 1 and type 2 diabetes, as well as in lifestyle recommendations, including dietary advice and physical exercise. The achievement of strict target levels, especially LDL-cholesterol values below 100 mg/dL, requires lipid lowering drug therapy. This LDL-cholesterol target level is based on the fact that diabetic patients reveal the same risk for myocardial infarction as non-diabetics after their first cardiovascular event. Thus the diagnosis of diabetes is regarded as an equivalent for manifest cardiovascular disease. The re-evaluation of large lipid intervention trials (4 S, CARE, LIPID, VA-HIT, Heart Protection Study) could clearly demonstrate also for the diabetic subpopulation that statin and fibrate therapy results in a significant reduction of the cardiovascular risk.

Pharmacology_Katzung

A 42-year-old woman has heterozygous familial hyper-cholesterolemia (HeFH) but is otherwise well and has no symptoms of coronary or peripheral vascular disease. A carotid ultrasound was normal. Her mother had a myo-cardial infarction at age 51 and had no known risk factors other than her presumed HeFH. The patient also has ele-vated lipoprotein (a) at 2.5 times normal and low HDL-C (43 mg/dL). She developed muscle symptoms with each of 3 statins (atorvastatin, rosuvastatin, and simvastatin) so they were discontinued although she did not develop elevated levels of creatine kinase. Her untreated LDL-C is 235 mg/dL and triglycerides 125 mg/dL. Her LDL-C goal for primary prevention of arteriosclerotic vascular disease is in the 70-mg/dL range because of her multiple lipopro-tein risk factors and her mother’s history of premature coronary artery disease. She has no other risk factors and her diet and exercise habits are excellent. How would you manage this patient?

Cholesterol

The 1987 report of National Cholesterol Education Program, Adult Treatment Panels suggests the total blood cholesterol level should be: < 200 mg/dL normal blood cholesterol, 200–239 mg/dL borderline-high, > 240 mg/dL high cholesterol. The American Heart Association provides a similar set of guidelines for total (fasting) blood cholesterol levels and risk for heart disease: Statins are effective in lowering LDL cholesterol and widely used for primary prevention in people at high risk of cardiovascular disease, as well as in secondary prevention for those who have developed cardiovascular disease.

[From prevention to cardiovascular rehabilitation: statins and evidence-based medicine].

The recent "Lipobay affair" prompted us to review the biomedical literature focusing on statins, in a prevention and rehabilitation perspective, and to prepare a pertinent evidence-based report. A number of randomized controlled clinical trials have assessed the efficacy and the safety of statins in cardiovascular prevention; these drugs have proved to be effective (number needed to treat values between 20 and 40) and safe (number needed to harm value for myopathy even when in association with fibrates around 833, as deduced from literature data). Fatal rhabdomyolysis is virtually not detectable in current scientific literature when statin therapy is administered in an appropriate fashion and when the patient undergoes periodical check-ups. In the individual patient, the benefits and risks related to his treatment have to be precisely tailored, evaluating his individual risk profile, the strength of the indication to statin therapy, the concomitant presence of other treatments and/or habits and the potential and actual adverse events foreseeable (to an extent) if established risk factors which predispose to myopathy are taken into consideration. The hematological lipids management strategy including a correct diet, physical exercise and statin therapy represents a key component of every evidence-based rehabilitation program too. Cardiovascular prevention and rehabilitation are major priorities at an individual as well as at a public health level. Both these strategies are based on a careful management of known risk factors, among them hypercholesterolemia, that today can be effectively and safely treated with statins.

Aseem Malhotra

The UK National Health Service website on healthy eating states that "Too much fat in your diet, especially saturated fats, can raise your cholesterol, which increases the risk of heart disease". This advice is part of a medical and dietary mainstream consensus about saturated fat shared with the World Health Organization and the health authorities of many other nations. Current guidelines for doctors from the UK National Institute for Health and Care Excellence for reduction of the risk of cardiovascular disease include giving advice on lifestyle changes before prescribing statins. The UK National Health Service website explains to patients that the lifestyle changes that doctors will recommend before prescribing statins include eating a healthy diet, exercising, stopping smoking, limiting alcohol and maintaining a healthy weight. Prof Mark Baker, Director of the Centre for Guidelines at NICE, stated that the use of statins in people with established heart disease was not

Hypertriglyceridemia: a case report from diagnostic laboratory, Barasat, West Bengal, India.

Hypertriglyceridemia is defined as an abnormal concentration of triglyceride in the blood and has been associated with atherosclerosis, even in the absence of hypercholesterolemia. This case report is of 40-year-old man diagnosed to have hypertriglyceridemia who attended for routine screening in our diagnostic laboratory at Barasat. He was nonsmoker, non-alcoholic, had a reasonable diet with abundant fruits and vegetables, and was on regular exercise. He was not taking any lipid lowering medications. He hailed from Barasat, and was employed in Government sector in Barasat and policeman by profession. His father died at the age of 57 years in a heart attack; but his mother is healthy and now almost 62 years of age, and he has two brothers one elder and another younger to him, both are healthy. His blood pressure was normal, his body-mass index was 27, and his waist circumference was 96 cm and hip circumference was 103. His waist/hip ratio was 0.932. The Biochemical analyses were as follows- Fasting Glucose: 186 mg/dL, Total Cholesterol: 90 mg/dL, Triglycerides: 372 mg/dL, High-density cholesterol: 3.80 mg/dL, Low-density cholesterol: 2.90 mg/dL, VLDL: 83.20 mg/dL, Cholesterol/HDL-C ratio: 23.6:1, LDL-C/HDL-C: 0.07:1. This study revealed the increased prevalence of dyslipidemia to be more prevalent in 31-40 year males, suggesting that this group is at an increased risk of developing CAD leading to young infarcts. Combination lifestyle therapies i.e., enhanced physical activity and dietary modification and therapeutic intervention would help us in the treatment and management of dyslipidemia.

[Results of studies of cardiovascular risk factors in 1875 visitors to the Frankfurt Health Days 1990].

In 1990 the Public Health Department of Frankfurt organised the third "Frankfurter Gesundheitstage" (Frankfurt Days for Health). Informations on healthy life style and prevention of diseases were available, as well as a screening programme for cardiovascular diseases. 1875 persons (1207 women and 668 men) had their total cholesterol, blood pressure and weight measured. They were asked about their age and body height, activities in sports, smoking behaviour, medications and their personal and family history for cardiovascular diseases. Mean age of the persons tested was 60 years (33% 40-59 yrs; 55% greater than 60 yrs). 13% of them smoked, 16% were obese. In 19% we found elevated blood pressure values, 5% of these values were not known before. 85% of the screened persons exhibited hypercholesterolaemia (greater than 200 mg/dl), and in 46% cholesterol exceeded 250 mg/dl. More than 25% of the hypercholesterolaemic values were not known before. Our data are not representative. Nevertheless, the results demonstrate that persons at risk can be reached by voluntary public screening programmes.

2017 Taiwan lipid guidelines for high risk patients.

In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG) levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, nicotinic acids (niacin), fibric acids derivatives (fibrates), and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS) and stable CAD, LDL-C < 70 mg/dL is the major target. A lower target of LDL-C <55 mg/dL can be considered in ACS patients with DM. After treating LDL-C to target, non-HDL-C can be considered as a secondary target for patients with TG ≥ 200 mg/dL. The suggested non-HDL-C target is < 100 mg/dL in ACS and CAD patients. For patients with ischemic stroke or transient ischemic attack presumed to be of atherosclerotic origin, statin therapy is beneficial and LDL-C < 100 mg/dL is the suggested target. For patients with symptomatic carotid stenosis or intracranial arterial stenosis, in addition to antiplatelets and blood pressure control, LDL-C should be lowered to < 100 mg/dL. Statin is necessary for DM patients with CV disease and the LDL-C target is < 70 mg/dL. For diabetic patients who are ≥ 40 years of age, or who are < 40 years of age but have additional CV risk factors, the LDL-C target should be < 100 mg/dL. After achieving LDL-C target, combination of other lipid-lowering agents with statin is reasonable to attain TG < 150 mg/dL and HDL-C >40 in men and >50 mg/dL in women in DM. LDL-C increased CV risk in patients with CKD. In adults with glomerular filtration rate (GFR) < 60 mL/min/1.73m<sup2</sup without chronic dialysis (CKD stage 3-5), statin therapy should be initiated if LDL-C ≥ 100 mg/dL. Ezetimibe can be added to statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia.

Dyslipidemia -- History and Physical

History is essential in identifying high-risk individuals. Most importantly, social history would include tobacco use or specific details about diet. Past medical history is vital in identifying patients who will need primary prevention versus secondary prevention if statin therapy requires initiation. Lastly, family history is important to identify familial hypercholesterolemia.

[Arterial hypertension and dyslipidemia in patients with chronic kidney disease (CKD). Anti-platelet aggregation. Goal oriented treatment].

TREATMENT OF ARTERIAL HYPERTENSION - Blood pressure (BP) should be regularly measured in all patients with CKD (Strength of Recommendation C). - BP control and proteinuria reduction delay progression of CKD (Strength of Recommendation A) and reduce cardiovascular risk (Strength of Recommendation C). Thus, control of both factors should be the treatment objective. - The BP target in patients with CKD should be < 130/80 mmHg, and 125/75 mmHg if proteinuria is > 1 g/24 hours (Strength of Recommendation A). - Lifestyle changes should be made: low-sodium diet (less than 100 mEq/day of sodium or 2.4 g/day of salt); weight reduction if patient is overweight (body mass index 20-25 kg/m2); regular aerobic physical exercise and moderate alcohol intake for BP control and prevention of cardiovascular risk (Strength of Recommendation A). - The choice of the antihypertensive drug in patients with CKD depends on the etiology of CKD, cardiovascular risk, or presence of clinical or subclinical cardiovascular disease (Strength of Recommendation A). - Two or more antihypertensive drugs are usually required to control blood pressure in patients with CKD (Strength of Recommendation B), and will frequently include a diuretic, which in stages 4-5 should be a loop diuretic (Strength of Recommendation B). - Renin-angiotensin-aldosterone system (RAAS) inhibitors are first choice drugs in patients with diabetic nephropathy, patients with non-diabetic nephropathy with a protein/creatinine ratio higher than 200 mg/g, and patients with heart failure (Strength of Recommendation A). The combination of ACEIs and ARBs is indicated for reducing proteinuria that remains high despite treatment with a RAAS inhibitor, provided potassium levels do not exceed 5.5 mEq/L (Strength of Recommendation B). - When RAAS blockers are started or their dose is changed in patients with advanced CKD, kidney function and serum potassium levels should be monitored at least after 1-2 weeks. DIAGNOSIS AND TREATMENT OF DYSLIPIDEMIA - A complete evaluation of the lipid profile including total cholesterol, LDL-C, HDL-C, and triglycerides should be performed in any patient with CKD at baseline and at least annually (Strength of Recommendation B). - In patients with stage 4-5 CKD and LDL-C >or= 100 mg/dL, treatment to decrease levels to < 100 mg/dL should be considered because of their high CV risk. This reduction is recommended in secondary prevention and in primary prevention in diabetic patients. Lipid-lowering treatment is recommended in all other patients, although no evidence showing its benefits is available yet (Strength of Recommendation C). - In patients with stage 4-5 CKD and triglyceride levels >or= 500 mg/dL which are not corrected by treating the underlying cases, treatment with triglyceride-lowering drugs may be considered to reduce the risk of pancreatitis. However, treatment with fibrates should be used with caution, and these drugs should not be associated to statins due to the risk of rhabdomyolysis (Strength of Recommendation C). There is little experience on the efficacy and safety of omega-3 fatty acids for the treatment of hypertriglyceridemia in patients with grade 4-5 CRF, but they may be considered a possibly safer alternative to fibrates (Strength of Recommendation C). SMOKING - Smoking is a cardiovascular risk factor and a risk factor for progression of kidney disease in patients with CRF (Strength of Recommendation B). - Use of active measures to achieve smoking cessation is recommended in patients with CRF (Strength of Recommendation C). HOMOCYSTEINE - Hyperhomocysteinemia has been postulated as a cardiovascular risk factor in the general population and in kidney patients, but the available evidence is not consistent. - There is no evidence that vitamin therapy decreases cardiovascular risk in patients with CRF, and recommendation of routine vitamin measurement and start of vitamin therapy to reduce cardiovascular risk in these patients is therefore questionable (Strength of Recommendation B). LEFT VENTRICULAR HYPERTROPHY - Left ventricular hypertrophy (LVH) is a cardiovascular risk factor in patients with CRF (Strength of Recommendation B). - It is advisable to perform an echocardiogram at baseline and every 12-24 months and to consider treatments allowing for LVH regression (Strength of Recommendation C). The approach to LVH should be early and multifactorial because its reversibility is limited once established (Strength of Recommendation C). - RAAS blockade with ACEIs or ARBs partially reverts LVH in patients with CRF (Strength of Recommendation B). ANTI-PLATELET AGGREGATION - Because of the high cardiovascular risk in patients with CKD, anti-platelet aggregant therapy, especially low-dose aspirin, would be indicated in patients with type 2 diabetes as primary prevention, and in all patients with CKD as secondary prevention. There is however no evidence of the benefits of anti-platelet aggregant therapy in primary prevention in patients with CKD, particularly in stages 4-5; indication for treatment in this situation should therefore be individualised because of its greater risk of bleeding. - Adequate good blood pressure control should previously be achieved to minimise the risk of haemorrhagic stroke (Strength of Recommendation C).

What do we gain by modifying risk factors for coronary disease?

There is no doubt about the association between coronary heart disease (CHD) and smoking, high serum cholesterol and high blood pressure, but association does not mean causation. To prove causation we must mount intervention trials and show that changing a risk marker changes total mortality: a) Trials of dietary reduction of serum lipids: The US Veterans dietary study and the North Karelia project showed no significant reduction in total mortality, nor did the Multiple Risk Factor Intervention Trial (MRFIT) or the WHO "paired-factories" Collaborative Group Study, where other risk factors were also being corrected. In the latter study there was a barely significant reduction in non-fatal CHD but fatal CHD, like total mortality was unchanged. b) Trials of lipid-lowering drugs: The first large-scale study, using clofibrate, showed an increase in total mortality; the screening of 500,000 men and the comparison of cholestyramine with placebo for the top 5% of lipid levels resulted in 68 deaths on the active resin and 71 on placebo. Less expensive measures (alcohol testing; safer roads) could surely do more good to half a million men? These 3 lives "saved" were "lost" in the Helsinki gemfibrozil study where there were 45 deaths in the active group and 42 in the placebo group. c) Effect of blood-pressure reduction. The assumption that reducing a risk marker will reduce CHD was challenged by the massive MRC Mild-to-Moderate Hypertension trial which showed no significant effect of treatment on CHD, CHD death or total mortality, even though stroke mortality was modestly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertriglyceridemia and residual dyslipidemia in statin-treated, patients with diabetes at the highest risk for cardiovascular disease and achieving very-low low-density lipoprotein-cholesterol levels.

As the result of the high prevalence of comorbidities and conventional risk factors among patients with type 2 diabetes (T2DM), most patients belong to the highest cardiovascular disease risk category, and have a target low-density lipoprotein cholesterol (LDL-C) of <70 mg/dL. Because substantial residual risk persists at LDL-C <70 mg/dL, a more comprehensive control of non-LDL-C and particles was recommended in the joint 2008 American Diabetes Association/American College of Cardiology Consensus. To ascertain, in statin-treated T2DM patients belonging to this greatest-risk group, with on-statin LDL-C <70 mg/dL, (1) the proportion of patients meeting all three critical levels (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol [HDL-C] <100 mg/dL, apoB <80 mg/dL) and (2) the variables associated with target attainment versus nonattainment. Among 675 unselected patients with T2DM, 367 were both at very high cardiometabolic risk and taking statins; 118 of these patient had LDL-C levels <70 mg/dL. Patients meeting all three criteria (LDL-C, non-HDL-C, and apoB; n = 79; all three at goal group) were compared with those only reaching LDL-C (n = 49; only LDL-C at goal group). LDL-C was 54 (12) for the all three at goal group versus 57 (10) mg/dL for the only LDL-C at goal group (NS). The two groups were similar regarding age, gender, diabetes duration, body mass index, waist circumference, blood pressure, renal function and micro-/macroangiopathy prevalence. A statin plus fibrate was given to 16% of patients in the all three at goal group and 32% in the only LDL-C at goal group. The two groups did not differ in baseline (prestatin) LDL-C, HDL-C, and non-HDL-C, except for pre-/post-lipid-lowering drug(s) triglycerides (TG): 177 (95)/118 (56) for all three at goal versus 279 (134)/ 241 (103) mg/dL for only LDL-C at goal (P = .0230 and P = .0001). The only LDL-C at goal group had lower HDL-C (vs. all three at goal): 41 (12) vs. 47 (14) mg/dL (P = .0237), with atherogenic dyslipidemia [hypo-HDL-C + hyper-TG] prevalence of 35% in the all three at goal versus 56% in the only LDL-C at goal group (P < .0001). log(TG)/HDL-C was 0.049 (0.021) for all three at goal versus 0.063 (0.021) for only LDL-C at goal (P < .0001). The LDL-C/apoB ratio was 0.92 (0.24) for all three at goal vs. 0.67 (0.18) for only LDL-C at goal (P < .0001), suggestive of smaller/denser LDL. The presence of atherogenic dyslipidemia was associated with a failure to meet all three critical modifiable targets for hypercholesterolemia, such a nonachievement being found in a large proportion (one-third) of very-high risk T2DM patients with very-low on-statin LDL-C. Attainment of all three targets will require (1) titration/permutation of statins, (2) lifestyle (re)inforcement; and/or (3) statin-fibrate bitherapy.

[When and how do we treat our hypercholesterolemic patients?].

To compare patients with hypercholesterolaemia (HC) for factors relating to the decision to treat a patient with medication or not; and to assess the suitability of a previously established protocol of HC diagnosis and treatment. Retrospective, descriptive study. Primary care centre. 331 patients diagnosed with HC in the register of risk factors at our centre. 175 patients treated with medication (TM) and 156 not treated with medication. Mean age was 61.2 and 191 were women. 68.8% of the population under study had 2 or more factors of cardiovascular risk (FCVR). 56 patients were in secondary prevention (71.4% TM). 275 patients (83.08%) were in primary prevention. 135 of these received TM, which was indicated only in 45 (37.5%). Mean plasma concentrations (PC) of cholesterol (total and LDL) were greater in the patients treated. 99.3% of non-treated patients and 96.9% of treated patients received dietary counselling. This was maintained in 95% of non-treated patients. The reduction of cholesterol in the PC reached 8% in diet-treated patients by the end of the study. Initially 42.8% were treated with fibrates, 38.9% with statins and 18.3% with resins. By the end of the study 53.6% were treated with statins. The association of HC and other FCVR is common. In primary prevention, a high proportion of patients treated present cardiovascular risk which does not justify medical prescription. In secondary prevention we are closer to the current guidelines.

Dyslipidemia

The three main blood levels collected to assess for dyslipidemia is triglycerides(TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C). High triglyceride levels (>1.7 mmol/L fasting) can indicate dyslipidemia. Triglycerides are transported through the blood by using very low density lipoproteins (VLDL) as a carrier. One thing to note when measuring triglyceride levels is that fasting for 8-12 hours is required to get an accurate result as non-fasting TG results may be falsely elevated. If TG results are greater than 10 mmol/L, then this needs to be addressed since severe hypertriglceridemia is a risk factor for acute pancreatitis. Another blood level collected to assess dyslipidemia is HDL-C. HDL cholesterol is made up of very little lipids and a high amount of protein. It is beneficial in the body because it functions by going to the tissues and picking up extra cholestrol and fat. Due to the positive effects of HDL-C, it is named "good

Pharmacologic treatment of type 2 diabetic dyslipidemia.

Patients with diabetes mellitus have a higher risk for cardiovascular heart disease (CHD) than does the general population, and once they develop CHD, mortality is higher. Good glycemic control will reduce CHD only modestly in patients with diabetes. Therefore, reduction in all cardiovascular risks such as dyslipidemia, hypertension, and smoking is warranted. The focus of this article is on therapy for dyslipidemia in patients with type 2 diabetes. Patients with the metabolic syndrome (insulin resistance) share similarities with patients with type 2 diabetes and may have a comparable cardiovascular risk profile. Diabetic patients tend to have higher triglyceride, lower high-density lipoprotein cholesterol (HDL), and similar low-density lipoprotein cholesterol (LDL) levels compared with those levels in nondiabetic patients. However, diabetic patients tend to have a higher concentration of small dense LDL particles, which are associated with higher CHD risk. Current recommendations are for an LDL goal of less than 100 mg/dl (an option of < 70 mg/dl in very high-risk patients), an HDL goal greater than 40 mg/dl for men and greater than 50 mg/dl for women, and a triglyceride goal less than 150 mg/dl. Nonpharmacologic interventions (diet and exercise) are first-line therapies and are used with pharmacologic therapy when necessary. Lowering LDL levels is the first priority in treating diabetic dyslipidemia. Statins are the first drug choice, followed by resins or ezetimibe, then fenofibrate or niacin. If a single agent is inadequate to achieve lipid goals, combinations of the preceding Drugs may be used. For elevated triglyceride levels, hyperglycemia must be controlled first. If triglyceride or HDL levels remain uncontrolled, pharmacologic agents should be considered. Fibrates are slightly more effective than niacin in lowering triglyceride levels, but niacin increases HDL levels appreciably more than do fibrates. Unlike gemfibrozil, niacin selectively increases subfraction Lp A-I, a cardioprotective HDL. Niacin is distinct in that it has a broad spectrum of beneficial effects on lipids and atherogenic lipoprotein subfraction levels. Niacin produces additive results when used in combination therapy. Recent data suggest that lower dosages and newer formulations of niacin can be used safely in diabetic patients with good glycemic control. Current evidence and guidelines mandate that diabetic dyslipidemia be treated aggressively, and lipid goals can be achieved in most patients with diabetes when all available products are considered and, if necessary, used in combination.

[Secondary prevention of coronary artery disease with lipid-lowering drugs].

Before the statins era, this was one of the most debated questions in the field of cardiology: although hypolipidemic drugs (mainly fibrates) decreased the cardiovascular morbidity and mortality, their influence on total mortality was not significant. The 4S study demonstrated the efficacy of a statin on cardiovascular morbidity and mortality and on total mortality. This was confirmed by the CARE and the LIPID trials. Statins should be prescribed to all coronary patients, whatever the type of coronary disease, the age (we do not know yet for people older than 80), the gender, the basal cholesterol level (maybe statins are not efficacious when it is<2g/l); cholesterol level has to be lowered below 2g/l. Two trials of drugs increasing the HDL cholesterol level were recently published. Unfortunately their results are contradictory. Statins should be the first level drugs. Maybe it is useful to decrease the triglycerides level and to increase the HDL cholesterol level. The association of a statin and a fibrate is reserved to specialized centers. We should not forget the usefulness of diet. We must also take the other risk factors into account.

Metabolic syndrome

EGIR The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following: Central obesity: waist circumference ≥ 94 cm or 37 inches (male), ≥ 80 cm or 31.5 inches (female) Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia Blood pressure ≥ 140/90 mmHg or antihypertensive medication Fasting plasma glucose ≥ 6.1 mmol/L NCEP The U.S. National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following: Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female) Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dl) Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female) Blood pressure ≥ 130/85 mmHg (or treated for hypertension) Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl)

[Guidelines for the treatment of hypercholesterolemia].

The prevalence of mild and moderate hypercholesterolemia among the middle-aged population of the G.D.R. is about 30%. Thus, this is the most important risk factor for coronary heart diseases. Primary therapeutic techniques are elimination of overweight, low-fat diet, rich in monoenic and polyenic acids, and increase of physical activity. When by these measures a decrease of cholesterol to 5.2-5.5 mmol/l is not achieved the introduction of lipid drugs is to be considered in dependence on the individual risk (associated risk factors like smoking, hypertension, diabetes, low HDL-cholesterol). In case of mild to moderate polygenic hypercholesterolemia cholestyramine, nicotinic acid and modern fibrates have the priority. Familial hypercholesterolemia demands as a rule the introduction of statins (e.g. lovastatin) or combinations of the above mentioned lipid drugs or the combination of cholestyramine and lovastatin, resp. In this way the prognosis even of patients with severe familial hypercholesterolemia can be improved decisively. Considering the fact that this would be a life-accompanying therapy a thorough consideration of the risk/benefit ratio and an adequate medical supervision are necessary.

Pharmacology_Katzung

Neal L. Benowitz, MD A 35-year-old man presents with a blood pressure of 150/95 mm Hg. He has been generally healthy, is sedentary, drinks several cocktails per day, and does not smoke cigarettes. He has a family history of hypertension, and his father died of a myocardial infarction at age 55. Physical examination is remarkable only for moderate obesity. Total cholesterol is 220, and high-density lipoprotein (HDL) cholesterol level is 40 mg/dL. Fasting glucose is 105 mg/dL. Chest X-ray is normal. Electrocardiogram shows left ven-tricular enlargement. How would you treat this patient?

First_Aid_Step2

■LDL > 130 mg/dL or HDL < 40 mg/dL, even if total serum cholesterol is < 200 mg/dL, is diagnostic of dyslipidemia. Based on risk stratification (see Table 2.1-11). Risk factors include diabetes (considered a CAD risk equivalent), smoking, hypertension, HDL < 40 mg/dL, age > 45 (males), age > 55 (females), and early CAD in first-degree relatives (males < 55 and females < 65). The first intervention should be a 12-week trial of diet and exercise in a patient with no known atherosclerotic vascular disease. Commonly used lipid-lowering agents are listed in Table 2.1-12. The BP goal in uncomplicated hypertension is < 140/< 90. For diabetics or patients with renal disease, the goal is < 130/< 80. Defined as a systolic BP > 140 mmHg and/or a diastolic BP > 90 based on three measurements separated in time (see Table 2.1-13). Classified as 1° or 2°.

Prevention of coronary heart disease. Part I. Primary prevention.

The first concern in primary prevention is the physician's belief that primary prevention is important for all adults and that intervention can significantly affect risk. Given the coronary plaque burden over many years and the importance of the development of healthy lifestyles early in adulthood to decrease coronary plaque burden, there are excellent reasons to begin prevention even with young adults. At the very least, a patient seen for any reason should provide a smoking history, have knowledge of the presence of early CHD in first-degree relatives and measurements of blood pressure, height, and weight, provide evidence for a cholesterol level within 5 years (after age 20 according to NCEP guidelines or in middle age according to ACP guidelines), and be given an assessment of glucose tolerance or diabetes. Information about alcohol intake and physical activity status are also of some importance. Other than height, weight, and blood pressure, during the physical examination, the physician should initially assess the strength of pulses in the lower extremities, evidence for carotid or femoral bruits, and eyegrounds for retinal arterial changes, and the skin and subcutaneous tissue should be examined for xanthomas and the eyes should be examined for corneal arcus and xanthelesma. These elements should be part of any initial examination by a primary care physician and are not extraordinary. In addition to lipid and blood sugar analyses, other evaluations may include blood urea nitrogen and creatinine and electrolytes in patients with hypertension or diabetes or in patients who are on antihypertensive agents. It may be prudent to obtain an ECG for patients who are older than 40 years. The elements mentioned above are the elements of the history, physical examination, and laboratory examination in subjects without a past history of CHD and with no clinical evidence for CHD. Primary prevention management begins with a discussion of risk factors with the patient. The key interventions aim at the lowering of blood pressure to at least less than 140/90 mm Hg, the complete cessation of smoking, the lowering of lipid levels to less than 130 mg/dL, the lowering of triglycerides to less than 200 mg/dL (or, some would argue, < 150 mg/dL), and the attempt to keep HDL cholesterol above 35 mg/dL (more than 40 to 45 mg/dL is a better goal) with the use of lifestyle modification. For patients with diabetes, strict control of glucose levels is essential to minimize disease of the microvasculature and possibly to minimize progressive renal disease. There are several lifestyle modifications for lipids. For patients with elevated LDL cholesterol, modifications include a less than 30% fat calorie diet and less than 300 mg of cholesterol intake daily, with fat calories approximately equally distributed among saturated fats, polyunsaturated fats, and monounsaturated fats (1/3, 1/3, 1/3; rule of 3s). The assistance of a dietician is extremely helpful in this regard. For patients with a low HDL cholesterol, weight reduction (for overweight patients) by calorie control and increased physical activity and smoking cessation will have some modest effect. For patients with elevated triglycerides, a diet similar to that for lowering of LDL cholesterol with the addition of stricter calorie limitation, avoidance of refined sugars, increase in complex carbohydrates, and avoidance of alcohol will be helpful. A decrease in the percent of fat calories to 20% to 25% will be of assistance to those patients with particularly high triglycerides. The treatment of underlying conditions such as diabetes mellitus, hypothyroidism, liver disease, and some renal conditions may also significantly modify high triglycerides. For patients with hypertension, limitation of sodium to 2 gm/d (6 gm sodium chloride), limitation of alcohol to 1 to 2 drinks a day, increased physical activity, and weight reduction are the key lifestyle modifications. (ABSTRACT TRUNCATED)

Management of hypertriglyceridemia.

Hypertriglyceridemia is associated with an increased risk of cardiovascular events and acute pancreatitis. Along with lowering low-density lipoprotein cholesterol levels and raising high-density lipoprotein cholesterol levels, lowering triglyceride levels in high-risk patients (e.g., those with cardiovascular disease or diabetes) has been associated with decreased cardiovascular morbidity and mortality. Although the management of mixed dyslipidemia is controversial, treatment should focus primarily on lowering low-density lipoprotein cholesterol levels. Secondary goals should include lowering non-high-density lipoprotein cholesterol levels (calculated by subtracting high-density lipoprotein cholesterol from total cholesterol). If serum triglyceride levels are high, lowering these levels can be effective at reaching non-high-density lipoprotein cholesterol goals. Initially, patients with hypertriglyceridemia should be counseled about therapeutic lifestyle changes (e.g., healthy diet, regular exercise, tobacco-use cessation). Patients also should be screened for metabolic syndrome and other acquired or secondary causes. Patients with borderline-high serum triglyceride levels (i.e., 150 to 199 mg per dL [1.70 to 2.25 mmol per L]) and high serum triglyceride levels (i.e., 200 to 499 mg per dL [2.26 to 5.64 mmol per L]) require an overall cardiac risk assessment. Treatment of very high triglyceride levels (i.e., 500 mg per dL [5.65 mmol per L] or higher) is aimed at reducing the risk of acute pancreatitis. Statins, fibrates, niacin, and fish oil (alone or in various combinations) are effective when pharmacotherapy is indicated.

Familial Hypercholesterolemia -- Treatment / Management -- Approach to Therapy

All patients with familial hypercholesterolemia and their families should receive education regarding lifestyle management. This includes a healthy diet, quitting smoking, and physical therapy/activity. Dietitians or nutritionists should advise patients and family members to reduce the amount of food with high cholesterol and encourage them to lose weight. [29] A holistic approach should be sought in the treatment of FH. Besides lowering LDL levels, controlling the patient’s lifestyle risk, and other modifiable risk factors of coronary heart disease is essential in reducing CV morbidity and mortality in these patients. Setting a suitable target LDL level is difficult, as patients with FH present with varying degrees of elevated LDL levels. Most guidelines recommend a reduction of 50% or more from the initial untreated LDL level in patients with FH. [30] [31] Some guidelines consider patients with prior coronary heart disease or concomitant diabetes are considered high risk, and the recommendation is to have an LDL level below 70 mg/dL, while patients without prior coronary heart disease or diabetes are considered the low-moderate risk and have recommended target LDL level below 100 mg/dL. LDL levels should be checked every 2 to 3 months while on treatment to adjust drug therapies accordingly. [32]

Management of dyslipidemia in the metabolic syndrome: recommendations of the Spanish HDL-Forum.

In order to characterize the metabolic syndrome it becomes necessary to establish a number of diagnostic criteria. Because of its impact on cardiovascular morbidity/mortality, considerable attention has been focussed on the dyslipidemia accompanying the metabolic syndrome. The aim of this review is to highlight the fundamental aspects of the pathophysiology, diagnosis, and the treatment of the metabolic syndrome dyslipidemia with recommendations to clinicians. The clinical expression of the metabolic syndrome dyslipidemia is characterized by hypertriglyceridemia and low levels of high-density lipoprotein-cholesterol (HDL-C). In addition, metabolic syndrome dyslipidemia is associated with high levels of apolipoprotein (apo) B-100-rich particles of a particularly atherogenic phenotype (small dense low-density lipoprotein-cholesterol [LDL-C]. High levels of triglyceride-rich particles (very low-density lipoprotein) are also evident both at baseline and in overload situations (postprandial hyperlipidemia). Overall, the 'quantitative' dyslipidemia characterized by hypertriglyceridemia and low levels of HDL-C and the 'qualitative' dyslipidemia characterized by high levels of apo B-100- and triglyceride-rich particles, together with insulin resistance, constitute an atherogenic triad in patients with the metabolic syndrome. The therapeutic management of the metabolic syndrome, regardless of the control of the bodyweight, BP, hyperglycemia or overt diabetes mellitus, aims at maintaining optimum plasma lipid levels. Therapeutic goals are similar to those for high-risk situations because of the coexistence of multiple risk factors. The primary goal in treatment should be achieving an LDL-C level of <100 mg/dL (or <70 mg/dL in cases with established ischemic heart disease or risk equivalents). A further goal is increasing the HDL-C level to >or=40 mg/dL in men or 50 mg/dL in women. A non-HDL-C goal of 130 mg/dL should also be aimed at in cases of hypertriglyceridemia. Lifestyle interventions, such as maintaining an adequate diet, and a physical activity program, constitute an essential part of management. Nevertheless, when pharmacologic therapy becomes necessary, fibrates and HMG-CoA reductase inhibitors (statins) are the most effective drugs in controlling the metabolic syndrome hyperlipidemia, and are thus the drugs of first choice. Fibrates are effective in lowering triglycerides and increasing HDL-C levels, the two most frequent abnormalities associated with the metabolic syndrome, and statins are effective in lowering LDL-C levels, even though hypercholesterolemia occurs less frequently. In addition, the combination of fibrates and statins is highly effective in controlling abnormalities of the lipid profile in patients with the metabolic syndrome.

[The influence of targeted intervention on the incidence of risk factors of cardiovascular diseases at medical staff].

The work addresses the targeted intervention of cardiovascular diseases at medical staff. SET AND METHODICS: During 2002-2004 years, within the scope of preventive examination, there was made targeted prevention of risk factors of cardiovascular diseases (CVD) at the big hospital employees at the Centre of preventive care of employees and in the department of preventive cardiology of Ist Internal Clinic of LF UP and FN Olomouc. According to the effective tables, there was stated a CVD risk of these employees. The employees received a personal individual letter which informed them of the level of CVD risk and proposed a targeted intervention of risk factors. The part of the set--427 employees of the average age of 38.93 years (SD 11.39), 69 men (M) of the average age of 40 years (SD 12.47) and 358 women (F) of the average age of 38.7 years (SD 11.18) was examined another time during 2004-2005 years. The methodics of second examination was the same as at the first examination, only the questionnaire was complemented by the questions related to the knowledge of the CVD risk stated at previous examination. There occurred statistically significant decrease of LDL cholesterol in the set (from 2.87 mmol/l to 1.23 mmol/l, p < 0.0001) and BMI decrease (from 24.35 to 24.16, p < 0.05) and at the same time statistically significant increase of total cholesterol (from 5.09 mmol/l to 5.27 mmol/l, p < 0.05) and triglycerides (from 1.27 mmol/l to 3.01 mmol/l, p < 0.0001). There was no significant change in other RFs (BP, WHR, HDL cholesterol, moving activity). The influence on RF of smoking was statistically significant (23 employees quitted smoking, 10 employees started, p < 0.05). 53 F (14.80%) and 3 M (4.34%) know their cardiovascular risk, 235 F (65.64%) and 53 M (76.81%) do not know their cardiovascular risk. The work approved the influence of targeted intervention on the incidence of cardiovascular diseases risk factors and at the same time low level of knowledge of one's own individual risk, despite of targeted intervention.

InternalMed_Harrison

1588 DYSLIPIDEMIA The treatment of dyslipidemia is central in aiming for long-term relief from angina, reduced need for revascularization, and reduction in myocardial infarction and death. The control of lipids can be achieved by the combination of a diet low in saturated and trans-unsaturated fatty acids, exercise, and weight loss. Nearly always, HMG-CoA reductase inhibitors (statins) are required and can lower LDL cholesterol (25–50%), raise HDL cholesterol (5–9%), and lower triglycerides (5–30%). A powerful treatment effect of statins on atherosclerosis, IHD, and outcomes is seen regardless of the pretreatment LDL cholesterol level. Fibrates or niacin can be used to raise HDL cholesterol and lower triglycerides (Chaps. 291e and 421). Controlled trials with lipid-regulating regimens have shown equal proportional benefit for men, women, the elderly, diabetic patients, and smokers. Compliance with the health-promoting behaviors listed above is generally very poor, and a conscientious

Metabolic Syndrome -- Treatment / Management

Patients with hypertriglyceridemia defined as triglycerides more than 150 mg/dL should be evaluated and further workup should include checking full lipid analysis, thyroid-stimulating hormone level, urinalysis, and liver function tests. After a comprehensive analysis, patients should first be counseled for lifestyle changes including abstinence from smoking, weight loss, and diet and exercise modification. Physicians will start treating hypertriglyceridemia once the level is above 500 mg/dL, and usually, patients have mixed dyslipidemia disorder by that point. Patients are usually on a moderate to high-intensity statin therapy first; however, fibrates, niacin, and omega acids are also available for treating hypertriglyceridemia. Elevated LDL should also be aggressively managed in these patients especially if the atherosclerotic cardiovascular disease (ASCVD) risk score if more than 7.5%, which establishes a patient’s 10-year ASCVD risk. These patients should be placed on high-intensity statin therapy with a goal of dropping the LDL by 50%.

New treatment options for lipid-lowering therapy in subjects with type 2 diabetes.

Dyslipidemias represent a variety of quantitative and/or qualitative lipoprotein abnormalities. According to etiology, we distinguish primary dyslipidemias with strictly genetic background and secondary ones with their origin in other disease or pathological states. Diabetic dyslipidemia is a type of secondary dyslipidemia and plays an important role in determining the cardiovascular risk of subjects with type 2 diabetes. In these patients, insulin resistance is responsible for overproduction and secretion of atherogenic very low density lipoprotein. In addition, insulin resistance promotes the production of small dense low-density lipoprotein (LDL) and reduces high-density lipoprotein (HDL) production. Cardiovascular disease remains a leading cause of morbidity and mortality in diabetic patients. Previous results support the role for small, dense LDL particles in the etiology of atherosclerosis and their association with coronary artery disease. Moreover, lowering LDL cholesterol reduces the risk of cardiovascular death. Therefore, the European guidelines for the management of dyslipidemias recommend an LDL cholesterol goal < 100 mg/dL in diabetic subjects without cardiovascular events. Moreover, if triglycerides (TG) are elevated (> 400 mg/dL), they recommend a non-HDL cholesterol goal < 130 mg/dL in diabetic individuals without cardiovascular events. Statins are the first line of LDL-lowering therapy in diabetic patients and combined therapy with ezetimibe and statins could be useful in very high cardiovascular risk diabetic subjects. Furthermore, the effect of a fibrate as an add-on treatment to a statin could improve the lipid profile in diabetic individuals with high TG and low HDL cholesterol. Regarding new therapies, recent data from phase III trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors considerably decrease LDL cholesterol. Thus, they may be useful in diabetic patients with concomitant diseases such as familial dyslipidemia, recurrent cardiovascular events, and elevated LDL cholesterol after second drug administration in addition to maximal statin dose or statin intolerance.