Lipids

Vascepa (fish oil) reduces ischemic cardiovascular events in high risk patients

Vascepa (fish oil) reduces ischemic cardiovascular events in high risk patients

The current study is of a major clinical significance as it shows that EPA lowers ischemic cardiovascular events by 25% in high rick CVD patients who are already receiving statin therapy. The EPA treated patients, however, experienced more hospitalizations for atrial fibrillation and a higher propensity for serious bleeding than placebo. Findings are remarkable as they come from a major randomized clinical trial (IMPROVE IT). About 8,000 patients were followed for 5 years.

This outcome data is in accordance with established observation and notion that hypertriglyceridemia is an independent risk factor for cardiovascular disease, mainly via increased inflammation and concentration of the non-HDL cholesterol. Prior clinical studies have also shown that EPA lowers non-HDL cholesterol more than DHA.

Omega-3s, EPA and DHA, are two key ingredients of fish oil. A stable and pure form of EPA has been FDA approved for very high serum triglyceride >500 mg/dL since 2012. It is marketed under the brand-name vascepa. Lovaza, a mixture of EPA and DHA, has also been approved by FDA since 2004 for severe hypertriglyceridemia.

I anticipate that in the future NLA, ACC/AHA, AACE and ADA guidelines will reflect and incorporate the current findings of IMPROVE IT.

GT

Lipoprotein(a), Familial Hypercholesterolemia and CVD

Lipoprotein(a), Familial Hypercholesterolemia and CVD

Familial hypercholesterolemia (FH) has a high prevalence of cardiovascular morbidity and mortality, due to the lifelong cumulative exposure of high serum cholesterol levels.

The study finds that only a minority of patients are capable of achieving LDLc targets set by the European guidelines. About 25% of FH patients reach LDLc ≤100 mg/dL and only 8% of very high-risk CVD patients reach LDLc ≤70 mg/dL.

Importantly, those with high Lp(a) experienced twice as much CHD events than those with low Lp(a) levels. Specific drug development toward Lp(a) would be a breakthrough in helping patients with familial hypercholesterolemia.

A group of 714 FH adults were followed for about 11 years.

GT

2018 Cholesterol Guidelines: Diabetes Mellitus

2018 Cholesterol Guidelines: Diabetes Mellitus

For diabetes patients, practical recommendations would be:

  • Start moderate-intensity statin therapy if:

    • Young, age 20-39, with microvascular complications or long-standing DM.

    • Older, age 40-75, without major risk factors.

  • Start high-intensity statin ± ezetimibe if the following factors are present with the goal of reducing LDLc ≥50%:

    • Multiple risk factors

    • ASCVD 10YR ≥20%

  • For adults >75, clinician-patient discussion is needed if statin were to be started or continued.

GT

2018 Cholesterol Guidelines: Severe Hypercholesterolemia

2018 Cholesterol Guidelines: Severe Hypercholesterolemia

An approximate solidifying recommendation:

  • For patients with severe hypercholesterolemia defined by baseline LDLc ≥190 mg/dL; target LDLc is <100 mg/dL. To achieve this target, patients could receive the following medications in the following order: max statin ± ezetimibe ± BAS ± PCSK9 inhibitor.

    • If baseline TGs >300 mg/dL, do not use BAS

    • If baseline LDLc is very high, >220 mg/dL, then target LDLc could be <130 mg/dL

GT

Familial Hypercholesterolemia and CVD risk factors

Familial Hypercholesterolemia and CVD risk factors

Genetic inability to clear LDL-particles leads to familial hypercholesterolemia. Persistent high serum LDLc and total-cholesterol are major cumulative risk factors for premature cardiovascular disease.

The article identifies other independent risk factors contributing to CVD in these patients. Such factors are male sex, smoking, hypertension, diabetes, elevated Lp(a), and family history of CVD.

Obviously, the modifiable contributors; hypertension, smoking and diabetes need to be managed aggressively.

GT

Statins improve diabetic retinopathy?

Statins improve diabetic retinopathy?

This major observational study suggests that statins reduce the risk of diabetic neuropathy, diabetic foot ulcers, and more importantly the risk of diabetic retinopathy. Risk reduction ranges from 10% to 45%. This could be due to statin-induced decreased microvascular inflammation. About 38,000 patients were followed for 7.5 years.

GT

2018 Cholesterol Guidelines: Secondary ASCVD Prevention

2018 Cholesterol Guidelines: Secondary ASCVD Prevention

Although current guidelines are an honest attempt in reflecting complex medical evidence from clinical trials, they may not be very practical or user-friendly to general practitioners.

A simplified but reasonable approach to lipid management for secondary ASCVD prevention would be:

  • Patients with established clinical ASCVD should achieve LDL-cholesterol <70 mg/dL by using statins ± ezetimibe ± PCSK9 inhibitors.

GT

LCAT, key to HDL particle formation

LCAT, key to HDL particle formation

Lecithin-cholesterol acyltransferase (LCAT) is a critical enzyme in cholesterol metabolism. It helps transport the cholesterol from the periphery, including diseased coronary arteries, back to the liver via formation of mature HDL particles (“good cholesterol”).

LCAT deficiency due to genetic mutations is rare. It leads to a profound low HDL-cholesterol level <10 mg/dL, in turn causing corneal opacities, target cell hemolytic anemia, and renal failure. Treatment is mainly supportive.

Authors have identified here an acquired immune-mediated form of LCAT deficiency. It is the 7th case worldwide. It caused nephrotic syndrome, but the patient responded well to the anti-inflammatory agent, prednisolone.

Although these are rare illnesses, they help us understand lipid physiology deeper, and more importantly to provide quick and efficient treatment.

GT

Certified Lipidologist

Certified Lipidologist

I am pleased to announce that, as of October 2018, I am a certified clinical lipidologist, accredited by the American Board of Clinical Lipidology (ABCL). The role of the lipidologist is to diagnose, treat, and manage patients with elevated cholesterol or triglyceride levels. Currently, there are approximately 700 certified lipidologists in the U.S.

Dyslipidemia is a major public health concern. Elevated cholesterol levels, particularly what’s called the “bad” cholesterol (LDLc) or non-HDL cholesterol are major risk factors for atherosclerotic cardiovascular disease leading to heart attack and stroke. World Health Organization estimates that globally, 45% of people have elevated total cholesterol.

Dyslipidemia could be monogenic, polygenic or due to comorbidities such as metabolic syndrome, insulin resistance, diabetes mellitus, chronic kidney disease, nephrotic syndrome, weight gain, lack of exercise, or use of other medications.

According to ABCL, I am 1 of 3 physicians in the U.S. who is certified in all three specialties; endocrinology/diabetes, hypertension and dyslipidemia. This allows me to provide comprehensive and detailed care to endocrine patients, particularly those with diabetes.

GT

2018 Cholesterol Guidelines: Key Points

2018 Cholesterol Guidelines: Key Points

Cardiovascular disease is the leading cause of death in the United States. Cholesterol anomaly, or dyslipidemia, is a major contributor to atherosclerosis morbidity and mortality. Multi-society new cholesterol guidelines were recently published. They were contributed and endorsed by ACC, AHA, ADA, and NLA, among other national associations. You can find below the key recommendations published in the journal of Circulation, November 2018.

GT

Leptin improves brain insulin resistance

Leptin improves brain insulin resistance

Leptin deficiency leads to weight gain, obesity, and insulin resistance. Leptin replacement in the form of metreleptin has been approved by the FDA for congenital or acquired generalized lipodystrophy. The current analysis reveals that metreleptin also improves central insulin sensitivity primarily via hypothalamus and to a lesser extent prefrontal cortex.

GT

Review of 2018 ADA guidelines: dyslipidemia in the context of diabetes

Review of 2018 ADA guidelines: dyslipidemia in the context of diabetes

ADA recommendations are released each January. Below is a succinct ACP review of guidelines in screening, treatment goals, lifestyle intervention, and drug approach to dyslipidemia in the setting of diabetes mellitus. LDL-cholesterol is still a main target. Charts depict indications and doses of statins, the mainstay therapy to diabetic lipid disorders.

GT

Benefits of zetia + zocor are enhanced in patients with diabetes

Benefits of zetia + zocor are enhanced in patients with diabetes

About 18,000 participants with acute coronary syndrome and LDL 50-125 received either zetia plus zocor, or zocor alone. After seven years of follow up, authors found that addition of zetia improved cardiovascular outcomes more in patients with diabetes then those without diabetes. Findings are consistent with the notion that diabetics are at higher baseline CVD risk.

GT

2017 ADA guidelines: dyslipidemia and diabetes

2017 ADA guidelines: dyslipidemia and diabetes

Below you can find ADA recommendations on screening, cardiovascular risks, and treatment of dyslipidemia in the context of diabetes. As always improve lifestyle choices first. If ASCVD likelihood is still high then add medications. Statins are first-line, either of moderate or high intensity. Statin selection would depend on age, CVD status, and contributing factors.

Statin plus PCSK9 inhibitor or statin plus zetia could be used in adults with residual ASCVD risk. Statin plus fenofibrate is no longer advised unless special circumstances are present; severe hypertriglyceridemia or in men with profound metabolic syndrome. Statin plus niacin is also not recommended due to stroke concerns.

For more details, ADA standards are listed below with a slightly modified wording for easier and succinct reading:

GT

New paradigm: how to treat diabetes in the context of cardiovascular illness

New paradigm: how to treat diabetes in the context of cardiovascular illness

Based on EMPAREG, LEADER, SUSTAIN, CANVAS and IRIS trials, authors propose a new treatment model for persons with type 2 diabetes and cardiovascular disease. The algorithm is listed below.

Metformin is still first-line therapy for those with A1c > 7.0%. SGLT2-inhibitors; jardiance or invokana should be prescribed next for adults with heart failure or cardiac atherosclerosis. However, patients with history of stroke or TIA should receive pioglitazone after metformin. GLP-1 agonists; victoza, saxenda or semaglutide are listed as third-line agents in this protocol.

The proposed paradigm is reasonable; however, cost, health insurance decree, side effects, added benefits, kidney function, route of administration, drug frequency and patient's preference also need to be considered.

GT

2017 NLA guidelines: PCSK9 inhibition and cholesterol

2017 NLA guidelines: PCSK9 inhibition and cholesterol

PCSK9 inhibitors are a relatively new class of medications. They lower atherogenic cholesterol and cardiovascular disease significantly. Although effective, cost limits their use to persons at high risk for CVD in spite of being optimally manged with statins (mainly crestor or lipitor).

National Lipid Association recently published the updated guidelines on the use of PCSK9 inhibitors in patients with residual CVD risk, very high LDL-cholesterol and those with intolerance to statin therapy. Recommendations are listed below with slightly modified wording for easier and succinct reading:

GT

Fish oil and cardiovascular mortality

Fish oil and cardiovascular mortality

Omega 3 fatty acids, mainly eicosapentaenoic and docosahexaenoic acids, seem to lower cardiac death by 8%. This meta-analysis includes 14 randomized clinical trials with a total of 72,000 subjects. 

Further benefits (13-29% death reduction) were seen in adults utilizing higher doses of omega 3 (> 1 gram per day) and in those with higher baseline cardiovascular risk; elevated triglycerides (>150 mg/dL), LDL-cholesterol (>130 mg/dL) and non-statin users.

Important to note that these results are to some degree in accordance with the recent Science Advisory from the American Heart Association published in March 2017, suggesting the use of omega three for secondary prevention of coronary heart disease, heart failure and sudden cardiac death.

GT

Coffee extends longevity

Coffee extends longevity

This major prospective study finds that coffee consumption reduces all cause mortality by 12% in men and 7% in women. About 500,000 participants were followed for 16 years.

More specifically, coffee intake seems to lower gastrointestinal death in men by 60%. In women however, the digestive, circulatory, and cerebrovascular disease mortality are reduced by 40%, 22% and 30% respectively, while raising the risk death by 30% from an ovarian cancer.

The study also uncovers the antiinflammatory effect of coffee on hepatic-insulin resistance axis, as documented by lower levels of AlkPhos, ALT, AST, GGT, CRP, Lp(a) and A1c in high consumers.

Unless side effects are present, coffee consumption promotes a good anti-inflammatory health.

GT

A massive trial on a new cholesterol medication: CETP inhibitor

A massive trial on a new cholesterol medication: CETP inhibitor

Cholesteryl ester transfer protein (CETP) is an important component of lipid metabolism. It helps exchange triglycerides and cholesterol between HDL and atherogenic particles (LDL, IDL and VLDL). Reduction or inhibition of CETP leads directly to both higher HDL-cholesterol and lower atherogenic particle concetrations. In principle, these lipid profile modifications are expected to reduce cardiovascular outcomes. 

To date, three CETP inhibitors (torcetrapib, dalcetrapib, evacetrapib) tested in clinical trials were either not effective in reducing CV outcomes or caused major adverse events. The current study published in NEJM September 2107 paints a different picture: anacetrapib 100 mg once daily lowered coronary events by 10% in patients with established CVD being treated with high intensity statin (atorvastatin/lipitor). Authors attribute these benefits primarily to non-HDL reduction of 17 mg/dL. Although HDL increased by 43 mg/dL, it is not considered causative or therapeutic.

Some unforeseen outcomes with anacetrapib were the subtle increase in systolic blood pressure of 0.7 mmHg, slight decrease in kidney function and lower incidence of new-onset type 2 diabetes. 

Study results are of major significance for several reasons. Some adults with very high baseline CVD risk (ex. prior myocardial infarction) still have residual chance for more coronary events even when receiving a high intensity statin such as atrovastatin or rosuvastatin. Thus an add-on medication like  anacetrapib could be useful. Importantly, results were derived from a massive amount of data involving ~30,000 participants over a 4 year period. Participants' baseline LDL-cholesterol (~60) and non-HDL-cholesterol (~90) were well controlled and balanced across study groups.

Given poor outcomes from other sister medications, I suspect more research is needed to fully elucidate the benefit/harm ratio for CETP inhibitors, and particularly for anacetrapib.

GT