Life is Full of Sweet Choices: Diabetes and the Heart

Diabetes Mellitus (DM) is a very common condition with wide ranging and severe complications. DM leads to metabolic and vascular diseases including coronary artery disease (CAD), cerebrovascular disease, peripheral artery disease, eye disease and kidney disease. This can progress to heart attacks, strokes, amputations, dialysis and blindness. What is DM, how does it affect the vascular system and how do we treat it?

 

DM is common and the eighth leading cause of death in the United States (US). In 2021, 38 million Americans (16%) had diabetes and 38% of the US had prediabetes. Those numbers continue to rise. Patients with DM are five times more likely to develop heart disease then those who do not have DM. 

 

DM is diagnosed by the following criteria: a hemoglobin A1c level > 6.5 % (hemoglobin A1c is a blood test that assesses the average blood sugar over the course of a month) or a fasting blood sugar level > 126 md/dl or any random blood sugar > 200 mg/dl. Prediabetes is a hemoglobin A1c between 5.7 and 6.4% or fasting blood sugar between 100 and 125 mg/dl.

 

The pathogenesis of DM is related to the actions of insulin, which is secreted by the pancreas and regulates the body’s blood sugar. Insulin lowers sugar (glucose) level in the blood and promotes increased uptake of sugar by the muscles for energy. There are two types of DM. Type 1 DM (5.7% of all DM) is caused by destruction of the cells used by the pancreas to make insulin.  In Type 2 DM, the body is resistant to the effects of insulin. If insulin is impaired by either mechanism, the blood sugar goes up. Longstanding high levels of blood sugar leads to inflammation of the blood vessels and impaired function of the blood vessels. Two types of vascular complications ensue: microvascular and macrovascular. Microvascular complications include retinopathy (eye disease), neuropathy (nerve pain) and nephropathy (kidney damage).   Macrovascular complications refer to inflammation and blockage in the heart, brain and peripheral arteries. 

 

The goal of management of DM is to achieve a hemoglobin A1c under 7%. This can be done through diet, exercise and weight loss. Working with a dietician can help find foods that are low in sugar. Weight loss of 5 to 10% improves hemoglobin A1c and lowers cardiac risk. Other risk factors should be controlled as well. Blood pressure should be lowered to less than 130/80 mmHg. If there is concomitant kidney disease or protein in the urine, an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin-receptor blocker (ARB) should be used as first line to delay the DM related progression of kidney disease.  Cholesterol should be lowered with a statin with a goal of LDL (low density lipoprotein, the “bad” cholesterol) under 70 mg/dl. High triglycerides often accompany DM. If the triglyceride level is above 150 mg/dl, then high dose fish oil (icosapent ethyl) can reduce cardiac risk.

 

There are many medications available for control of blood sugar. Insulin injection is used to treat Type 1 DM. For Type 2 DM, especially for those with heart disease, three classes of medications are preferred.  Treatment is usually begun with metformin. Metformin decreases glucose production by the liver, reduces the uptake of sugar in the gastrointestinal system and improves insulin sensitivity by increasing glucose uptake in the muscles. Metformin can help with weight loss and improve vascular function. Sodium glucose cotransporter-2 inhibitors (SGLT2) include Jardiance and Farxiga. These agents increase the excretion of glucose by the kidneys. SGLT2 agents have been shown to reduce cardiac events, cardiac mortality, heart failure hospitalizations and slow the progression of kidney disease. Glucagon-like peptide-1 receptor agonists (GLP1) also treat Type 2 DM and have similar beneficial effects on the heart as the SGLT2 agents, lowering major cardiac events. These agents also help with congestive heart failure and delay progression of disease in chronic kidney patients. Of course, GLP1 agonists are used to treat obesity, even in patients without DM. GLP1 agents include semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). They act by having the pancreas release insulin only when the blood sugar is high, stopping secretion of glucagon (which tells the liver to release sugar into the blood), slowing the movement of food from the stomach (preventing spikes in blood sugar) and controlling hunger and food craving to help lose weight.  GLP1 agents improve multiple risk factors for atherosclerosis including lowering weight, improving fat distribution (for example, decreasing waist circumference), lowering blood pressure, improving lipids and decreasing inflammation. Because of these factors, GLP1 agonists can lower the risk for major cardiac events by 20%.

 

Type 2 DM is preventable with lifestyle modifications. Effective lifestyle management includes watching calorie, carbohydrate and fat intake in the diet, maintaining a good body weight and exercising.  In patients with obesity and high risk for DM, these lifestyle changes lowered the risk for DM by 34% over a ten-year period. If lifestyle isn’t working, the use of the GLP1 agonist semaglutide lowered the risk for DM by 73% in obese patients.

 

Life is full of sweet choices. One choice you should make is to try to avoid Type 2 DM and its myriad complications. So, choose to exercise regularly, watch your weight and keep the sweets to a minimum.

What Can a Reverend Who Lived in the 1700’s Teach Us About Heart Artery Disease Today?

 

 

“It’s tough to make predictions, especially about the future”

 

The quote about predictions is from noted philosopher (and Yankees Hall of Famer) Yogi Berra. One person who can help us make predictions, Thomas Bayes, was a Presbyterian minister.  He was born in 1701 in England and studied theology and logic at the University of Edinburgh. He worked as a minister but continued to dabble in questions of logic until he died in 1761. After he passed away, his family found a paper that he wrote and brought it to the attention of the Royal Society. The paper described what came to be known as Bayes Theorem. Bayes Theorem launched a new way of thinking and Bayesian probability has become the core of modern statistics. In 2018, the University of Edinburgh dedicated their informatics department to Reverend Thomas Bayes. Bayes Theorem gives a way to work out conditional probabilities. A conditional probably is the probability of an event A, given that condition B is true; what is the probability of A given B.  In other words, it takes a belief, evaluates new evidence and gives a new, improved belief.  Scientists believe that human brains use a type of Bayesian thinking to deliberate and decide. Bayesian reasoning has exploded with uses in many diverse areas including physics, ecology, psychology, artificial intelligence and even self-driving cars. One of the fields where Bayes Theorem is most useful is in medicine. 

 

Consider the case of a 50-year-old man who comes to his doctor’s office for evaluation. What is the probability of coronary artery disease (CAD) for this man? In 1979, the New England Journal of Medicine published a landmark study introducing Bayes Theorem to the medical community. The article asked exactly this question; how can the probability of CAD be calculated in a 50-year-old male patient? From population studies and autopsies, the probability of CAD for a 50-year-old male is 7% (for comparison the probability of CAD in a 50-year-old woman is 1.6%, for a 65-year-old man it is 12%). Next, we learn of a new finding, our 50-year-old man has been having chest pain. Suppose he is having symptoms that are typical of angina pectoris. We know that being 50 years old and a male he has a probability of CAD of 7%. Now we have new information, he has chest pain, typical angina.  We can evaluate with Bayes equation and find that his probability of CAD is now 90%. If his symptoms are more atypical, then his probability of CAD is only 53%. If he has atypical chest pain, but has a positive stress test, then his probability goes back up to 70%. Contrast that with a 30-year-old man who has a low baseline probability (0.03%). Even if the 30-year-old has typical chest pain, his probability of CAD is only 26%.  This is the power of Bayes, the probability of a disease can be revised up and down based on each piece of new information. 

 

The most important factor in determining the risk for CAD is baseline characteristics (pre-test probability). Age and sex give a crude estimate. More sophisticated calculators have been developed that incorporate more variables (for example diabetes, blood pressure, cholesterol, smoking, family history). These include the Framingham risk score, the American College of Cardiology (ACC) risk calculator, the Pooled Cohort equations and the most recent iteration, the PREVENT equations. These tools are accurate but they have drawbacks. They give a 10-year estimate for the risk for a heart attack (rather than providing a risk for CAD right now) and are not useful in all populations (for example, they are less accurate in lower socioeconomic groups). In addition, they may not be able to predict a first heart attack.  A study analyzed 465 patients under 65 years old without known CAD who presented with a heart attack. The patients’ information was entered into the ACC risk estimator and the PREVENT calculator. The researchers found that 45% of the patients would have classified as low risk with ACC calculator, meaning no further testing or statin advised. For the PREVENT calculator, 61% would have been classified as low risk. Predicting the future is hard.

The next most important factor is symptoms (for example, chest pain).  Remember that our 50-year-old man (baseline 7%) having typical chest pain, has a probability of CAD of 90%.  The characterization of the chest pain is vitally important as it will shift the probability (and therefore the work up and treatment) of CAD significantly. Typical angina pectoris (chest pain) is exertional, described as a tightness or squeezing or pressure or heaviness or dull aching located in the area of the breast bone. The pain can radiate to the left arm, neck, jaw or back. It will usually last a few minutes and be relieved by rest. Atypical pain is sharp or stabbing, located on the right side and brought on by deep breathing or change in position.  There is a substantial population of patients who continue to have typical angina despite having no severe blockage on heart catheterization. This problem has vexed clinicians for more than 40 years. After years of research, we now have a better understanding of this syndrome (microvascular dysfunction) and a catchy moniker, ANOCA (Angina, NOrmal Coronary Arteries). Catheterization will evaluate for blockage in the main heart arteries, but catheterization only shows about 10% of the total heart circulation. The rest consists of small vessels, the microvasculature. The small vessels are the primary site of regulation of blood flow to the heart muscle. When the heart needs more oxygen (for example while running) the microvasculature dilates and the flow increases. With ANOCA, that regulation is abnormal and patients will have classic chest pain when the demand is greater than the supply. ANOCA patients have predictable triggers of chest pain such as exertion or emotional stress. It is more common in women, in smokers, and people with hypertension or high cholesterol. ANOCA is common, occurring in about 25% of all heart catheterizations and affecting about 3 to 4 million Americans. It is diagnosed after the large heart arteries are found to be normal. A stress test with PET imaging or heart catheterization with specialized testing will diagnose ANOCA. 

 

So, if you have chest pain, you can calculate your probability of CAD by entering your variables into Bayes equation, or enter the data into a Bayes app (it does exist!) or checking a table. However, the prudent course would be to call your doctor and ask what tests are necessary. If you continue to have classic angina despite normal arteries on heart catheterization, then seek out a cardiologist specializing in ANOCA (they do exist!).