“The Good Cholesterol” May Not be so Good After All

Remember when we used to tell patients that high-density lipoprotein cholesterol (HDL-C) was “healthy” of the “highly desirable lipoprotein”? Well, a number of research studies in recent years have caused cardiovascular and lipid experts to say that the information obtained about HDL via epidemiology led us in the wrong direction.

One pharmaceutical company lost almost a billion dollars when it’s trial of a cholesterol ester transfer protein (CETP) inhibitor more than doubled HDL-C but patients in the treatment group had a higher death rate, so the trial was halted early as raising HDL-C failed to provide benefit.  Other clinical trials that used niacin, which significantly increases HDL-C but doesn’t significantly increase HDL particle number, failed to improve cardiovascular clinical outcomes. This in turn led authors of the American College of Cardiology (ACC) not to recommend niacin in the March 2016 clinical guidelines regarding the role of non-statin therapies in the management of cardiovascular risk.

A more recent study by Sharif and colleagues published in the May issue of Diabetes Care sought to find out if low HDL-C was a risk factor for cardiovascular disease and mortality in subjects with type 2 diabetes mellitus. They also wanted to find out if low HDL-C would remain a residual risk factor in those on intensive lipid-lowering therapy and/or if LDL-C goals were met.

Data was obtained from a cohort (n=1829) of subjects with diabetes enrolled in the Second Manifestations of ARTerial Disease (SMART) trial.  LDL-C levels were stratified into three groups: <77 mg/dL, 77-97 mg/dL, and >97 mg/dL and the intensity of their lipid-lowering therapy. Adjustments were made relating to confounding variables such as BMI, gender, age, triglycerides, LDL-C, HbA1c, glucose, estimated glomerular filtration rate,  alcohol, and smoking.  During the (median) 7 years of follow-up, there were 335 new cardiovascular events and 385 deaths. The investigators found no relationship between HDL-C levels and cardiovascular events. In fact, in their conclusion they stated that they unexpectedly found that subjects with Diabetes and LDL-C levels <77 mg/dL and higher HDL-C at baseline had an increased risk of cardiovascular events and all-cause mortality.

So… gone are the days when we can simply say that HDL is “good”. Experts continue to marvel at the recent discoveries related to the complexity of the proteomics and lipidomics of HDL cholesterol.  In order to prevent events, we need to move beyond HDL-C measurements. Research is currently underway to help us understand how HDL functions and how we can better identify those who are at a higher cardiovascular risk based on HDL functionality rather than on the amount of cholesterol found in the HDL particle.

Stress in the Amygdala, Cardiovascular Risk, and Inflammation

Although psychological stress has been linked to cardiovascular disease risk for years, our understanding of the connection continues to grow.  Dr. Ahmad Tawakol and colleagues at Massachusetts General Hospital in Boston presented information at the 2016 American College of Cardiology sessions from a study they did in 293 patients who had PET/CT scans between 2005 and 2008.  Subjects who had evidence of cancer, established cardiovascular disease or who were younger than age 30 were excluded.  This first-of-kind study revealed a relationship between amygdala activity in the brain, associated with stress and fear, and arterial inflammation.  In addition to objective measurements of brain activity, the scans allowed for measurements in arteries and bone marrow.  Over approximately a 5 year study period and after correction for cardiovascular risk factors based on Framingham Risk and age and gender, investigators found that 35% of the subjects in the high amygdala activity group had a cardiovascular event, whereas only 5% in the low amygdala activity group suffered such.  Dr. Tawakol proposed that perhaps the activation of the amygdala, bone marrow, and arterial inflammation together contribute to a mechanism that may lead to cardiovascular events.  In his concluding remarks, Dr. Tawakol stated that the risk of heart disease linked to stress is on par with other major risk factors.   Further studies are needed, but perhaps those of us interested in the prevention of cardiovascular events might want to evaluate inflammatory biomarkers in our patients who are under stress in an effort to uncover hidden risk and/or subclinical cardiovascular disease.

See: Signs of Stress in the Brain May Signal Future Heart Trouble …

Should we add Migraine Headaches to the CV Risk Factor List?

A recent prospective study based on data from 115,541 women free of known cardiovascular disease (CVD) who were enrolled in the Nurses’ Health Study II was published in the British Medical Journal.  The researchers sought to determine if there was a link between migraine headaches and incident CVD and CVD mortality in women.  Of the subjects enrolled, 15.2% (n=17,531) had physician diagnosed migraine headaches.  Subjects with diagnosed migraines ranged in age from 25-42 years and were followed for over 20 years with a cumulative follow-up rate >90%.  Despite adjustment for potential confounders, migraine headaches were strongly associated with incident stroke (hazard ratio 1.62, 1.37 – 1.92), coronary revascularization procedures/angina (1.73, 1.20 – 2.32), myocardial infarction (1.39, 1.18 to 1.64) and CVD mortality (1.37, 1.02 – 2.32).  These associations held across various subgroups of women by age (<50/≥50 years) and whether or not they had hypertension or were on oral contraceptives or post-menopausal hormone replacement therapy.

The investigators concluded that there was a strong consistent link between CVD events, including CVD mortality, and migraine headaches and recommended that women with migraine headaches be more aggressively evaluated for vascular risk (and subclinical disease.)

Study Shows Colchicine Use in Patients with Gout May Reduce Cardiovascular Event Rates

It is well known that cardiovascular event rates are higher in patients with various inflammatory conditions. A recent study by Dr. Daniel Solomon and colleagues at Harvard revealed an apparent link between large reductions in cardiovascular events in 501 patients with gout who used colchicine over a 16.5 month period vs. 501 similar patients with gout who did not use colchicine. Read more Study Shows Colchicine Use in Patients with Gout May Reduce Cardiovascular Event Rates

Are Lipid Targets Back?

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Guidelines, based solely on a limited number of randomized controlled clinical trials with statin therapies, recommended reductions of LDL-cholesterol (LDL-C) by >50% or 30-50% for various populations based on trial data and clinical outcomes.  The authors of the document stated they were “not for or against targets” ….but not including guidelines with cholesterol targets or goals led to confusion and controversy amongst experts, clinicians, and patients. Read more Are Lipid Targets Back?

New Study Shows Portfolio Diet Lowers BP (in addition to LDL-C & hsCRP)

Dr. David Jenkins and colleagues have now shown that a variation of the Portfolio Diet (viscous fiber, soy protein, plant sterols, and almonds) proven to lower LDL-C and hsCRP in 2003, also lowers blood pressure (BP). Previous studies had alluded to this potential benefit, so Jenkins et al. looked at pooled data from a study that compared a DASH-type diet to intensive application of the portfolio diet in 241 hyperlipidemic subjects. Read more New Study Shows Portfolio Diet Lowers BP (in addition to LDL-C & hsCRP)

Recent Study Shows Nutraceuticals Improve Abnormal LDL-C

Since statins are often discontinued due to tolerability problems, a study of dyslipidemic patients (n=100) post percutaneous coronary intervention by Marazzi and colleagues published in the Journal of the American College of Cardiology sought to determine the value of a combination of nutraceuticals (policosanol, folic acid, red yeast rice, berberine, astaxanthin and coenzyme Q10) called Armolipid Plus, with or without ezetimibe in getting these patients’ low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. Read more Recent Study Shows Nutraceuticals Improve Abnormal LDL-C

New Research Reveals the Hazards of a Southern Dietary Pattern

According to recently published research in the journal Circulation, Shikany and colleagues sought to find out if the risk of acute coronary heart disease (CHD) was associated with dietary patterns. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) trial data base (n=17,418) was used.  Subjects were enrolled in this national, population-based trial that was conducted in both white and black adults between 2003 and 2007. Read more New Research Reveals the Hazards of a Southern Dietary Pattern

Nonobstructive CAD, Women, and Prevention of Cardiovascular Events

Cardiologists are acknowledging the need to better refine cardiovascular risk assessment in women.  According to information recently published in the Journal of the American College of Cardiology, women are more likely to have nonobstructive coronary artery disease (CAD) than men.  Since nonobstructive CAD, characterized by soft plaque, is known to precede plaque rupture that can lead to devastating cardiovascular events, there is reason for practitioners to pay attention to these gender differences. Read more Nonobstructive CAD, Women, and Prevention of Cardiovascular Events

Study Associates Chronic Dysglycemia (HbA1c ≥ 5.8%) with Inflammation, Endothelial Dysfunction, and Higher Cardiovascular Event Rates post STEMI

Many prevention specialists believe that we are not diagnosing diabetes early enough if we wait for hemoglobin A1c (HbA1c) levels to reach ≥ 6.5%.  Filepe Moura and colleagues sought to find out if there was a relationship between HbA1c  levels in non-diabetic ST-elevation myocardial infarction (STEMI) patients and recurrent cardiac events.  Read more Study Associates Chronic Dysglycemia (HbA1c ≥ 5.8%) with Inflammation, Endothelial Dysfunction, and Higher Cardiovascular Event Rates post STEMI

Does the Mediterranean Diet Also Reduce Risk of Heart Failure and Stroke?

Although the Mediterranean Diet is recommended to help reduce the incidence and mortality of cardiovascular disease in general, data on how it affects heart failure and stroke rates is lacking. In a population-based cohort in Sweden, investigators questioned 32,921 women via dietary questionnaires.  Read more Does the Mediterranean Diet Also Reduce Risk of Heart Failure and Stroke?

New Evidence about the Role of Inflammation in Promoting Coronary Atherosclerosis

A recent study published in the journal Atherosclerosis involved investigating epicardial adipose tissue (EAT) pathology, as determined by neoangiogenesis and inflammation, and atherosclerosis in the coronary arteries as determined by computed tomography (CT) imaging. Read more New Evidence about the Role of Inflammation in Promoting Coronary Atherosclerosis

Is Now the Time to Target Both LDL and Inflammation?

According to the Expert Opinion of Peter Libby, MD, internationally renowned for his work in cardiovascular disease research and just published in the journal Cardiology, “In an era of precision medicine, the ability to target either LDL or inflammation, or both, depending on an individual’s biomarker profile, should allow us to personalize therapy in the secondary prevention of coronary heart disease.” Read more Is Now the Time to Target Both LDL and Inflammation?

Analysis Reveals Lipoprotein “little a” [Lp(a)] Independently Predicts Stroke

According to a study published recently in the journal Atherosclerosis, Lipoprotein (a) is a risk factor for ischemic stroke.  The meta-analysis conducted by Alexander Nave, et. al., reviewed data from 20 articles (studies that did not differentiate between hemorrhagic and ischemic stroke were excluded) that included 90,904 subjects and 5029 stroke events. Read more Analysis Reveals Lipoprotein “little a” [Lp(a)] Independently Predicts Stroke

Study Shows Increased Systemic Inflammation Linked to Risk of Recurrent Heart Attack

It is well known that those who have just had a heart attack are at highest risk for future events.  The “culprit” lesion for the event, may not, however be the only one lurking in the near term, just the only one exposed at the moment.  A recent study published in the Journal of the American Heart Association was designed to investigate systemic atherosclerotic acceleration in relation to the acute inflammatory response surrounding acute myocardial infarction (MI).  Read more Study Shows Increased Systemic Inflammation Linked to Risk of Recurrent Heart Attack

“Treat to Target” BP Study Halted Early Due to Reductions in CV Event and Death Rates

According to officials at the National Institutes of Health (NIH), the Systolic Blood Pressure Intervention Trial (SPRINT) was stopped early due to a stunning improvement in cardiovascular outcomes in the group treated to a target systolic blood pressure (BP) of 120 mm Hg as compared to the “standard of care” control group treated to <140 mm Hg.  Read more “Treat to Target” BP Study Halted Early Due to Reductions in CV Event and Death Rates

Are Revolutionary New Drugs on the Horizon to Reduce CV Risks?

What you “need to know” about PCSK9 Inhibitors

Several new drugs that significantly reduce low density lipoprotein (LDL) cholesterol levels have recently been recommended by experts for approval by the Federal Drug Administration (FDA).  Many are optimistic about the approval of alirocumab (suggested trade name Praluent) on July 24th and evolocumab (suggested trade name Repatha) on August 27th.   Read more Are Revolutionary New Drugs on the Horizon to Reduce CV Risks?

Fasting Triglycerides Point to Risk After Acute Coronary Syndrome

A post-hoc analysis of data from two large studies that enrolled subjects post-acute coronary syndrome (ACS) was recently published in the Journal of the American College of Cardiology. Investigators sought to find out if there was a relationship between baseline fasting triglyceride (TG) levels, prior to randomization, and major cardiovascular events. Read more Fasting Triglycerides Point to Risk After Acute Coronary Syndrome

Can Circulating Vitamin D Levels Provide Useful Information about Coronary Artery Disease status?

Research published in Nutrition, Metabolism, and Cardiovascular Diseases examined data from 375 patients undergoing coronary angiography between November 2012 and September 2013. For this study, a diagnosis of coronary artery disease (CAD) was defined as the presence of ≥50% stenosis in at least one major coronary artery. Read more Can Circulating Vitamin D Levels Provide Useful Information about Coronary Artery Disease status?

Inflammatory Markers and Adiponectin Help Define Risk – Looking Beyond Traditional Risk Factors

A recent study published in the Journal of Clinical Endocrinology and Metabolism touts the value of looking at inflammatory biomarkers in determining risk in obese and non-obese adults.  The study included an almost equal number of men and women ages 45-74 (n = 2047). Read more Inflammatory Markers and Adiponectin Help Define Risk – Looking Beyond Traditional Risk Factors

Study Shows Pure EPA Reduces OxLDL, Lp-PLA2 and hsCRP

A review of data from both the MARINE and ANCHOR trials reveals that a new prescription omega-3 product available in the US significantly reduces inflammatory biomarkers.  This pure ethyl ester EPA product (trade name Vascepa) is approved for lowering triglycerides in patients with triglycerides >500mg/dL.  Read more Study Shows Pure EPA Reduces OxLDL, Lp-PLA2 and hsCRP

Newly Published Studies Point to Links between Low Vitamin D levels, Fatal Cardiovascular Events, and Inflammation

Authors of a study published in Diabetes and Endocrinology reviewed data from 172 randomized controlled trials and 290 prospective cohort studies to determine if low vitamin D levels [i.e., 25(OH)D] were causally related or consequentially related to ill health. Read more Newly Published Studies Point to Links between Low Vitamin D levels, Fatal Cardiovascular Events, and Inflammation

Recently Published Commentary on New Cholesterol Guideline from Cleveland Clinic Preventive Cardiology Section

Cleveland Clinic has been ranked #1 in Heart Care since 1995 and continues to do so. In response to the new ACC/AHA cholesterol guideline in an issue of the Cleveland Clinic Journal of Medicine, physician leaders in the Section of Preventive Cardiology presented a review of the recent ACC/AHA guideline on the treatment of blood cholesterol. Read more Recently Published Commentary on New Cholesterol Guideline from Cleveland Clinic Preventive Cardiology Section

High Omega-3 Serum Biomarker Levels Associated with Significantly Decreased Risk for Diabetes

Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to lower triglyceride levels, inflammatory biomarkers, and cardiovascular risk. Data related to PUFAs and risk for diabetes has been inconsistent, perhaps due to imprecise evaluations related to dietary self-reports. Read more High Omega-3 Serum Biomarker Levels Associated with Significantly Decreased Risk for Diabetes

Problems in Risk Estimates for Patients with Rheumatoid Arthritis

Investigators in the Netherlands looked at 4 tools for calculating cardiovascular risk in patients with rheumatoid arthritis (RA) and found that the Reynolds risk score, Systematic Coronary Risk Evaluation, and the Framingham risk score may underestimate risk in patients with RA. Read more Problems in Risk Estimates for Patients with Rheumatoid Arthritis

Study Reveals Value of Galectin-3 and NT-proBNP in Predicting Heart Failure and Death

Researchers for a study published in the February 1, 2014 issue of the American Journal of Cardiology investigated a combination of biomarkers and various other factors (e.g., hypertension, atrial fibrillation, etc.) in patients (n = 706) with known cardiovascular disease to determine their predictive value for cardiovascular events. Read more Study Reveals Value of Galectin-3 and NT-proBNP in Predicting Heart Failure and Death

Low Levels of Vitamin D Linked to Inflammation

Investigators from Ireland have published results of an observational study (n=957) conducted in hypertensive adults >60 years of age in the Journal of Clinical Endocrinology and Metabolism which clearly links low levels of 25-hydroxy vitamin D [25(OH)D] with several markers of inflammation, including high-sensitivity C-reactive protein (hsCRP). Read more Low Levels of Vitamin D Linked to Inflammation

Higher Serum Uric Acid Levels Can Predict CVD Progression

In a study (n=368) of post-menopausal women with no known cardiovascular disease (CVD), published in the April issue of the American Journal of Cardiology, R. Calvo and his colleagues compared baseline levels of Uric Acid with Coronary Artery Calcium (CAC) scores obtained via Electron Beam Computed Tomography (EBCT) at baseline and again after 5 years. Read more Higher Serum Uric Acid Levels Can Predict CVD Progression

High Blood Pressure and Low Vitamin D Levels

In a meta-analysis published in The Lancet Diabetes & Endocrinology, investigators examined gene variants known to be involved in vitamin D synthesis as well as the availability of the substrate for Vitamin D and found that “each 10% increase in vitamin D concentration was associated with lower systolic and diastolic blood pressure readings and a reduced odds of hypertension”. Read more High Blood Pressure and Low Vitamin D Levels

More Reasons to Know Your Vitamin D Level…Higher Levels May Promote Longer Life

A recent meta-analysis of 8 studies conducted in either the United States or Europe found that in men and women, ages 50-79 who did not smoke, those with “inadequate vitamin D levels” were at greater risk of dying early from cardiovascular and/or all-causes. Read more More Reasons to Know Your Vitamin D Level…Higher Levels May Promote Longer Life

Internationally Recognized Lipid Expert Critiques the 2013 ACC/AHA Cholesterol Guideline

In the field of cardiovascular risk reduction and Lipidology, Dr. Scott Grundy is one of the best renowned experts in the world. Dr. Grundy is past chair of the 2001 National Cholesterol Education Program Adult Treatment Panel III guidelines, recipient of numerous awards including the Distinguished Achievement Award in 2010 by the National Lipid Association, and lead author on the current Global Recommendations for the Management of Dyslipidemia published by the International Atherosclerosis Society. Read more Internationally Recognized Lipid Expert Critiques the 2013 ACC/AHA Cholesterol Guideline

Review of Study Data shows “Lower (LDL) is Better”

The July 28th issue of the Journal of the American College of Cardiology included a new meta-analysis of eight clinical trials of patients on statin therapy (n=38,153). Since no randomized clinical trials have been designed to look at clinical outcomes based on LDL targets, investigators looked at data from these clinical trials and decided that a mean LDL-cholesterol (LDL-C) level of 175 mg/dL would serve as the reference group. Read more Review of Study Data shows “Lower (LDL) is Better”

To Fast or Not to Fast? Interpretation of the Standard Lipid Profile

A headline in a recent issue of the New York Times suggested that “fasting before a lipid panel may offer no clinical value.” Indeed, non-HDL-cholesterol (now regarded as a better indicator of cardiovascular risk by the International Atherosclerosis Society and many other lipid experts) does NOT require fasting. Read more To Fast or Not to Fast? Interpretation of the Standard Lipid Profile

Is Infertility Related to Low Levels of Vitamin D?

According to research published in the August online issue of the Journal of Clinical Endocrinology and Metabolism, women (n=345) who were attempting to conceive via in vitro fertilization had significantly greater success rates of high quality embryo implantation and clinical pregnancy if vitamin D levels were 20ng/mL or more vs. those with levels less than 20ng/mL. Read more Is Infertility Related to Low Levels of Vitamin D?

Albumin/Creatinine Ratio Helps Predict Heart Attack Risk in Patients with Type 1 Diabetes

A model has been developed by researchers in the United States and Europe to predict the risk of major complications [stroke, coronary heart disease (CHD), end-stage renal disease, amputation, and death] in subjects (n=1973) with Type 1 Diabetes. Read more Albumin/Creatinine Ratio Helps Predict Heart Attack Risk in Patients with Type 1 Diabetes

United States Preventive Services Task Force Recommends Increased Testing for Diabetes

The US Preventive Services Task Force (USPSTF) has published new draft guidelines recommending all adults over the age of 45 years be screened for type 2 diabetes.  Previous guidelines for diabetes screening published in 2008, recommended that primary care physicians focus on screening patients with high blood pressure. Read more United States Preventive Services Task Force Recommends Increased Testing for Diabetes

NT-proBNP as a Predictor of Heart Failure in Patients with Chronic Kidney Disease

Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) can predict heart failure (HF) in the general population, investigators sought to find out if NT-proBNP could be used to predict HF in patients with mild to severe chronic kidney disease (CKD).  Read more NT-proBNP as a Predictor of Heart Failure in Patients with Chronic Kidney Disease

Elevated Urinary Microalbumin Creatine Ratio Associated with Worse Outcomes

In another recently published study, this one in the Journal of the American College of Cardiology: Heart Failure, investigators sought to see if there was a relationship between the urinary microalbumin creatinine ratio (UACR) and cardiac structure and/or function in patients with heart failure.  Read more Elevated Urinary Microalbumin Creatine Ratio Associated with Worse Outcomes

New National Guidelines Discuss Measuring Inflammatory Biomarkers to Identify Increased Stroke Risk

The American Heart Association/American Stroke Association (AHA/ASA) just published new guidelines for the primary prevention of stroke that acknowledge the relationship between inflammation and various stages of the atherogenic process including initiation, progression, and stability of atherosclerotic lesions.  Read more New National Guidelines Discuss Measuring Inflammatory Biomarkers to Identify Increased Stroke Risk

Patients with Nonalcoholic Fatty Liver Disease May Warrant Additional CV Risk Assessment

Researchers at Massachusetts General Hospital and Harvard Medical School in Boston reviewed data from the Rule Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT) II Trial to expand on the knowledge linking inflammation to atherosclerosis and see if there was an association between nonalcoholic fatty liver disease (NAFLD) and high-risk plaques.  Read more Patients with Nonalcoholic Fatty Liver Disease May Warrant Additional CV Risk Assessment

Currently Recommended Risk Models Fail to Identify Heart Risk in Patients with Rheumatoid Arthritis

New data published in the journal Arthritis and Rheumatology suggests that the cardiovascular risk (CV) prediction models recommended for use in the general population fail to identify over half of patients with rheumatoid arthritis (RA) who are at high cardiovascular risk.  Read more Currently Recommended Risk Models Fail to Identify Heart Risk in Patients with Rheumatoid Arthritis

Inflammatory Activity Linked to Increased Cardiovascular Risk in Subjects with Crohn’s or Ulcerative Colitis

A study released October 17, 2014 in the on-line version of Circulation: Cardiovascular Quality and Outcomes relates levels of activity (remission vs. activity vs. flares) of inflammatory bowel disease (IBD) in patients discharged after their first heart attack with risk of future cardiovascular events and death.  Read more Inflammatory Activity Linked to Increased Cardiovascular Risk in Subjects with Crohn’s or Ulcerative Colitis