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The Impact of Genetics in Cardiovascular Disease

Claude-K-LardinoisIn part 1 of this exclusive interview from AACE 2016, Dr. Claude Lardinois discusses amputations and SGLT-2s, and genetic risk factors for cardiovascular issues in diabetes patients.

Joy Pape: Hi this is Joy Pape. I am at the AACE convention 2016 in Orlando, Florida. We have with us today?

Dr. Lardinois: My name is Claude Lardinois.

Joy Pape: So tell us, what brings you to AACE for this convention?

Dr. Lardinois:  Well, actually, I came to AACE this year because I’m getting an award. I’m getting the Fellow of the American College of Endocrinology, the FACE award, and many of my colleagues have reminded me that I do need a new face. So I’m picking it up. But I actually got the award two years ago, but you’re required to attend the meeting and I take my wife to Hawaii in May. We had already booked the last two years so if I would have told her I have to come to an AACE meeting instead of going to Hawaii, I probably wouldn’t have any reason to come home anymore. So this year we cut our vacation a week short. We were supposed to come home today; we came home on Sunday, so that I could get the award Saturday night.

Joy Pape: So we asked you a question earlier in this talk about the SGLT-2s and amputations. What’s your take on this?

Dr. Lardinois: Well, unfortunately, there’s been a lot of hype. What was reported was, they do these interim analyses and the monitoring board is very careful in reporting this. They just noticed that there seem to be more toe amputations or amputations in the patients taking the Invokana, the SGLT-2 Invokana, than the placebo. Now, the numbers were very, very small. I don’t know exactly but 4 and 5 and 3 and maybe 2 or 6, 4, 2 or something, but it wasn’t a huge difference and it’s occurred more in the patients who were on the 100 mg than were on the 300 mg Invokana. And there were some thoughts maybe why that may be, because of the volume changes that occur with the drug. The safety monitoring board did not feel that the studies should be terminated for that reason. Now, I asked a question, because I think smoking is a huge factor in amputations. In fact, I personally think that in my practice anyway, 90% of the patients that have amputations are the ones that continue to smoke. So, I asked that question, but because the study is an ongoing blinded study, they can’t give us that information. But I will make a hypothesis that the patients that had the amputations were probably smokers.

Joy Pape: So, how do you teach your patients about foot care and preventing amputations?

Dr. Lardinois: We have a policy that you have to get your shoes and socks off immediately when you get in the room. I’ve shown this, I’ve worked in the University of Nevada for many years and took emeritus status recently. I would tell the patients, when you go see your primary care doctor, you take your shoes and socks off and if he ignores you then you have my right to put your feet on his desk. Put them up on his desk and say inspect my feet. So we inspect the feet every time we see the patients. When I have patients that are smokers, I look at their leg and I’m checking for sensory and that and I say, do you like your legs? Well of course, Dr. Lardinois, I like my legs. Well if you keep smoking, you’re not going to have your legs. I say, do you know what a black and decker is? Well yeah. We might as well do a black and decker right now. Because that’s what’s going to end up happening if you keep smoking. I’m amazed because I’ve actually had patients that have quit smoking. I just saw one of my patients not too long ago, and the nurse said your black and decker’s here today. She laughed, she said you got me to quit smoking, because you emphasized to me the importance of my legs.

Joy Pape: This could be very interesting. You might come up with some very interesting ways of getting people motivated to manage their diabetes better. Something else we were talking about earlier [was] about cardiovascular disease. Or just managing diabetes and the topic of genetics. Tell me more.

Dr. Lardinois: Let’s talk about diabetes and cardiovascular disease, because if you look at patients with diabetes and patients without diabetes, the only difference is one has an elevated blood sugar, the other does not. So, intuitively, the thought process was, particularly from the ADA, is if you lower the glucose to normal, your heart disease will go away. Doesn’t happen. You still have heart disease, because it turns out it’s not the glucose, it’s that you have insulin resistance. I’ve been accused by my colleagues that I’m really not an endocrinologist, I’m a cardiologist disguised as an endocrinologist, because I really don’t get too hung up about the blood sugar. I don’t have to have it 6.5 or 7. I tell my patients, you are going to die of heart disease. So my important things for you are: what are the things that are going to drive your heart disease? Blood pressure. I’m a very big believer in blood pressure control. Lower is better. Again, you have to be careful in some elderly patients. But cholesterol is very important, measuring albumin in your urine is very important. So these are all factors, but even after we do that, we’re still evaluating people as a group, not as an individual. That’s where the genetics come in. There are certain genetic tests that everybody should have done, whether you have diabetes or not. Some of those are Apo-E [tests]. Apo-E is a very important gene that really determines what type of nutritional recommendations you’re going to make for your patient. If you’re a 2-2 or a 2-3, or if you’re a 3-3 or a 3-4, it’s going to vary on what the nutritional recommendations are. Another thing is, we always talk about alcohol as being good for you — modest alcohol consumption. If you’re an Apo-E 4 and 25% of the population has either 3-4 or 4-4, alcohol actually makes your cholesterol worse and it increases cancer, particularly breast cancer in women. Some of my colleagues say I’m not going to measure my Apo-E 4, because I like alcohol. You’re going to tell me I can’t drink anymore. But we have to explain to those patients that they really have to limit their alcohol to one drink a day. So that’s very important nutritional information, right from the start, that you would never get by just following the standard guidelines.

There’s other genetic markers. There’s actually a statin marker — a lot of controversy behind it. But I stand firm that there’s a certain gene that we have called KIF6, and if you don’t have the variant, the studies with two of the cholesterol drugs weren’t very compelling, that they lowered LDL, but they didn’t reduce heart disease. So I tell a lot, if you don’t know what your KIF6 variant is, which most doctors don’t (I know mine), you have to be very discretionary in which statin you prescribe. Then there’s other genes that you could also look at. One is haptoglobin; haptoglobin is how we carry our oxygen around. It turns out that there’s three different haptoglobins, 1-1, 1-2, and 2-2. Well, patients with type 2 diabetes who have 2-2, have a 45 percent increased cardiovascular event rate. So again, that’s why I think with cardiology, we have these studies, even if we aggressively treat their lipids, we still have this 30% residual. Well, I don’t think that residual is cholesterol. I think it’s haptoglobin, APO-E, maybe the statin that you’re prescribing; other factors, albumin in the urine. I think albumin in the urine is a powerful risk factor for heart disease. But unfortunately the FDA doesn’t see it as a good primary endpoint. I think until they do that, and actually establish a primary endpoint for that, we will never get a valuable answer. There’s no question about albumin in the urine. People think it’s just the kidney, albumin in the urine is the kidney telling you, you have endothelial disease. That you are leaking albumin throughout your entire body. That albumin drives cardiovascular disease. Big time.

Joy Pape: So, do you refer your patients for genetic counseling? If this is the way you practice, how do you learn more about their profile?

Dr. Lardinois: Right now it’s been kind of challenging. The diabetes [practice] I was in, they were not all that receptive. Change is always hard to do. So I actually worked with two of my former medical students, who are now practicing physicians in Reno. There’s a concierge service. I helped them set-up a genetic thing, so if patients do want to come in, they pay cash now. It’s only $1000 for the genetic testing. You do a treadmill which is $1100, and that doesn’t tell me anything. I think treadmills are kind of useless. I went 16 minutes on the treadmill, and I’ve got heart disease. I went 16 minutes. Well they’d tell me I’m just fine. Well, I’d be dead now. That’s what happened to the guy on Meet the Press. He had a treadmill [test] and three days later he was dead. What was his name? I’ll think of it in a second. [ed. note: Tim Russert.] Right now, it’s been hard to get it implemented, and I’m moving to a different position in a different hospital and maybe I can get involved with a cardiologist and get this up and running. I do think there’s basic genetic testing that should be implemented in the management of everybody with any disease, and it’s not that expensive.

Joy Pape: So we talk about patient education and people making changes. Behavior change. So how did it work? How does it work if your patients find they have this certain gene and they need to cut down on their drinking? Have you had any experience with that?

Dr. Lardinois: Oh yeah, some of them aren’t really happy with that. But I say, I provide you a service. I’m not your mom or your dad and I provide you a service and I say based on this information, you should reduce your alcohol consumption to one drink a week.

Joy Pape: Is it effective?

Dr. Lardinois: In some people it is. I think 70% of patients will follow along with you, but I think 30% no matter what you do [won’t]. There’s patients that I say [to], I feel sorry, I feel bad today. They say why? You came in, I gave you these recommendations three months ago, you didn’t do any of them. Your A1C, your blood pressure, your cholesterol, your kidney test is all the same. I’m going to have to charge you $75 for this. We live in Nevada, you could go to a nice big buffet with your whole family for $75. So I feel kind of bad, I’m taking their money away because why did they even bother to come? They didn’t do anything.

Joy Pape: Well, I’m sure glad you came today. I think it’s obvious why you got this award that you’ll be getting tonight. So congratulations and thank you.

Dr. Lardinois: Just one other point I’d like to share that I think is important. One of the things I try to do is, I work with the VA to try to set up ways to get doctors to better manage their [patients’] diabetes. I actually came up with this thing called PENTAD. I published it in Archives of Family Medicine. It was very short. Just a little card, a pocket card. The P stood for Proteinuria, which would be albumin. The E stood for Eyes. Make sure you have your patients get their eye exam. N was necklace or bracelet. Make sure they have a bracelet. T was toes, check the toes. The A was A1C. And then you say well it’s PENTAD, you have the D, so what’s the D? I said that you Document in the chart that you did the PENTA. I was very successful. It worked very well. I was going through some old papers of mine and I came up and had a few of my PENTAD cards left that I did. I did camps for kids with diabetes for 18 years and I think Lilly or somebody nicely made these PENTAD cards, so we just gave them out to everybody.

Joy Pape: It’s great to have those memory tags, something to remember.

Dr. Lardinois: We actually had a stamp. We had a stamp at the VA where we just stamped the PENTAD in and you could just write it in. That improved compliance tremendously, because it’s a reminder.

Joy Pape: I know it’s something I’ll use. Thank you so much.

Read part 2.