On Monday 5 November 2018, whilst attending a routine screening appointment with my practice nurse at the local GP surgery, I had a heart attack. The pain started between my shoulder blades, and at first I thought it was indigestion, no pain down my left arm, no sweating, no shortness of breath. But it soon became clear that this pain was more than indigestion when it became so severe it hurt to move.
Five days later, following an angioplasty and stent to a blocked left anterior descending artery (LAD) often called the ‘widow maker infarction’ due to a high death risk, I embarked on trying to find out why this has happened (FIG 1).
At 65 years old, 5ft 1’ in height, 51kgs weight, non-smoker, non-drinker and married to a chef that insists on healthy eating and home cooked foods, my ‘cardiac risk’ profile would appear to be extremely low. So, what triggered my heart attack?
Risk factor one. In the maternal branch of my family, my mother and grandmother experienced heart issues; a pulmonary embolism and heart attack in their 60s and both died of a stroke following a life spanning 93 years and 80 years respectively. There is significant evidence to confirm inherited genetic cardiac risk factors do run in families.[i]
Risk factor two. Could my cholesterol level be an issue, which is a waxy substance that’s found in the fats (lipids) in the blood? The body needs cholesterol to continue building healthy cells but having high cholesterol can increase the risk of heart disease.[ii] Lipids include various types of cholesterol, phospholipids, and triglycerides and are carried in the blood as lipoproteins. High lipids increase the risk of blood clots, heart disease and heart attack, stroke, and pancreatitis. [iii] A phone call to my HIV specialist nurse, confirmed that my low-density lipoproteins (LDL) or “bad” cholesterol recorded a result of 8mmol/L in January 2018. The recommended level should be LDL-cholesterol of 2mmol/L or less for those at high risk[iv]. A high LDL leads to a buildup of cholesterol in the arteries. However, there is another important measurement of cholesterol which looks at the high-density lipoproteins (HDL) or good cholesterol, which removes excess cholesterol via the liver. My records showed an HDL of 2.3mmol/L, which is good in comparison to the recommended level of 3mmol/L or less for those at high risk. Finally, I needed to know my overall cholesterol level through dividing the LDL by the HDL to achieve an overall cholesterol level of 3.48mmol/L, which is below the recommended 4mmol/L or less for those at high risk. It would appear then my HDL is making a significant difference to my overall cholesterol level but I remained concerned about why my LDL is so high. Is there another reason for such a high profile?
Risk factor 3. Could my antiretroviral medication (ART) prescribed to keep my HIV viral levels low and undetectable be an issue? I have been on Darunavir 800mgs and Ritonavir 100mgs since 2010. This ‘monotherapy’ combination has suited my lifestyle through its once a day low pill burden which improved adherence and tolerability due to its lack of side effects. Darunavir is always used in combination with the HIV medicine ritonavir (brand name: Norvir) and other HIV medicines. Darunavir belongs to a class of HIV drugs called protease inhibitors (PIs). PIs block an HIV enzyme called protease. By blocking protease, PIs prevent HIV from multiplying and can reduce the amount of HIV in the body.[v]
Ritonavir inhibits the activity of the gut and liver enzymes that break down protease inhibitors and clear them from the body. Taking a low dose of ritonavir alongside another protease inhibitor therefore increases the concentration of the other protease inhibitor in the blood and maintains it at effective levels in the blood for longer.[vi]
There is a growing body of evidence that reports ritonavir is associated with various drug interactions and side effects, including lipid abnormalities, which clearly doesn’t help those living with dyslipidemia (abnormal amount of lipids.)[vii] Darunavir /Ritonavir also include side effects of: diabetes and high blood sugar (hyperglycemia), changes in body fat (including gain or loss of fat).
Research seeking to compare the efficacy, safety, and impact on lipid fractions of switching from a ritonavir-boosted protease inhibitor (PI/r) to a dolutegravir (DTG) regimen in virologically suppressed HIV type 1 patients with high cardiovascular disease risk was non-inferior and significantly improved lipid profiles. [viii]
The D:A:D study, a large prospective cohort study designed to look for serious non-AIDS events including cardiovascular risk of HIV drugs, examined data from 35,711 HIV positive people with follow-up data from 2009 (approximately 70% of the original D:A:D cohort). The current analysis looked at the currently used protease inhibitors atazanavir and darunavir. The study found cardio vascular disease (CVD) impact of darunavir/ritonavir was cumulative with longer duration of use, particularly people who used darunavir/ritonavir for more than six years. [ix]
Risk factor 4. Am I doing all I can to improve my Quality of life (QOL)? What are the risk factors of ageing and CVD? Evidence suggests that as you age the risk of developing heart disease increases with about four out of five people dying of coronary heart disease being 65 or older.[x] It makes sense when you age that your internal mechanisms for the circulation of blood also age and become harder to flow the blood around the body, resulting in fatty deposits developing along the artery walls. How then do I assess my risk of developing CVD as a 65-year old woman?[xi]
The Framingham Risk score is one gender-specific algorithm used to estimate the CVD risk of an individual. A quick on line assessment that looked at my age, gender, non-smoker, total cholesterol & HDL, systolic blood pressure and non-medication treatment of B/P suggests that my risk of developing heart disease in the next ten years is less than 1 - 5%.[xii] [xiii]
Another assessment tool is to check my Body Mass Index (BMI) scale by dividing my weight in kilograms by height in metres, therefore 51.2kgs divided by 1.549 metres and then divided again by height resulted in a BMI of 21.3. [xiv] Double checking with the NHS UK online tool that asked for my age, height, weight, fitness level confirmed that my BMI suggests I am a healthy weight for my height. The next measurement is my waist circumference to check if I am carrying too much fat on my stomach which can raise my risk of heart disease and stroke. According to the NHS website, regardless of your height or BMI, you should try to lose weight if your waist is: 94cm (37ins) or more for men, 80cm (31.5ins) or more for women and you are at very high risk if your weight is: 102cm (40ins) or more for men, 88cm (34ins) or more for women. Fortunately, my waist is 26 ins or 66cms so I am not depositing fat on my waist.
According to the NHS guidelines for older adults over 65 with no health issues that limit mobility should try do:
- at least 150 minutes of moderate aerobic activity such as cycling or walking every week and
- strength exercises on 2 or more days a week that work all the major muscles (legs, hips, back, abdomen, chest, shoulders and arms)
- 75 minutes of vigorous aerobic activity such as running or a game of singles tennis every week and
- strength exercises on 2 or more days a week that work all the major muscles (legs, hips, back, abdomen, chest, shoulders and arms)
- a mix of moderate and vigorous aerobic activity every week (for example, two 30-minute runs plus 30 minutes of brisk walking equates to 150 minutes of moderate aerobic activity) and
- strength exercises on 2 or more days a week that work all the major muscles (legs, hips, back, abdomen, chest, shoulders and arms)[xv]
My fitness level has diminished this year from a daily routine 3-mile walk that I religiously undertook but stopped when my neighbour moved to a new house, who used to accompany me. Yet, I still meet at least 150 minutes of moderate aerobic activity walking each week but probably could do more with strength exercises.
My next analysis is my dietary intake and saturated fats. We use vegetable oils lightly in cooking and occasionally on salad dressing. A small amount of fat is an essential part of a healthy, balanced diet. Fat is a source of essential fatty acids, which the body can’t make itself. Fat helps the body absorb vitamins A, D and E. These vitamins are fat-soluble, meaning they can only be absorbed with the help of fats.[xvi] I am not a lover of saturated fatty food, sausages, red meats, pies, lard, cream, cakes and pastries, crisps, popcorns but I do like boiled sweets, cheese and Thai food that contains coconut cream. I eat at least one Thai meal a week using light coconut milk, buy fish and chips once a month and sometimes a chicken wrap from McDonalds and eat a biscuit in a morning with a cup of tea with green top milk but I do try to eat healthily and I do not drink any alcohol.
Risk factor 5.
Sleep and stress can affect the heart. According to the British Heart Foundation stress is not a direct risk factor for coronary heart disease or heart attacks.[xvii] Fortunately, I sleep well having on average 8 hours per night. There is evidence from research that has demonstrated an association between psychological factors such as stress and the development of coronary heart disease. [xviii] Mental health and HIV infection are closely intertwined with a body of evidence associating high levels of mental ill health within key populations such as men who have sex with men (MSM), injecting drug users (IDUs), sex workers and trans population.[xix] But what about my own health as a woman? I do not see myself as having any mental ill-health but I do associate with occasional stress, particularly following the birth of my one and only nearly two-year old grandson who I care for 2 to 3 days each week. He has been in and out of hospital over the winter months with very worrying chest infections and has an intense allergy to dogs. Alongside my grandson, my two sons also invested in a dog each, Daisy, a pug and Eddie, a Boston Terrier who come to stay with us through the day. On their own they are no bother, but when the three of them come for a day, it is constant stress, trying to keep the dogs away from my grandson, on top of the constant mess and disruption to our home. Has this added to my heart condition?
Risk factor 6.
A study conducted from 2001 to 2009 at Zuckerberg San Francisco General Hospital found that sudden cardiac death among people living with HIV was more than 4.5 times higher than among people in a similarly-matched HIV-negative population. Chronic inflammation is a symptom of HIV infection, that persists even when a person is on treatment with a suppressed viral load. And inflammation predicts cardiovascular problems in people living with HIV, although Priscilla Hsue shared that the underlying cause is still not known.[xx] So should PLHIV be prescribed statins as a preventative method, like people with diabetes? A retrospective study of older people outlined results that do not support the widespread use of statins in old and very old populations, but they do support treatment in those with type 2 diabetes younger than 85 years. [xxi] However, older generations of protease inhibitors, may contribute to CVD risk. Dyslipidemia is a well-known complication of HIV infection and ART. Typically, HIV-infected patients have a lipid profile characterized by elevated levels of triglycerides, low-density lipoprotein cholesterol (LDL-C), total cholesterol and reduced levels of high-density lipoprotein cholesterol (HDL-C)[xxii] [xxiii] Is there now a case for preventive statins in those people with HIV at risk through the side effects of ART, genetic risk profile of CVD, age or lifestyle?
My recent and life threatening heart attack has catapulted my health into another dimension that will impact on my future for ever. I will be on statins for life and other cardiac medication. Polypharmacy is another educative tool that I now explore to ensure acute, primary and community clinicians are informed of my complicated health needs. My search for answers to find the cause of my sudden and almost final life episode has identified many potential risk factors that need recognition as I age. My journey now begins in seeking to educate and inform others of the multiple risk factors, the screening tools for health disease that exist and how CVD can be prevented for many others living with HIV.
This review of my heart attack is multifactorial and could have occurred from several reasons. The ‘widow-making’ severe blockage to my heart goes beyond my seemingly fit and healthy lifestyle and could have been caused through maternal genetics, my current ART treatment, to some extent increasing age and changes in my mental health/stress levels. What is clear that when a person living with HIV presents following a heart attack in a clinical environment, it is vital to have joined up care services with the person at the centre of the care pathway to gain a full picture of their health, social, physical and mental care needs. And is there a need to seek to address the potential risk of CVD in PLHIV and use statins as a preventative method?
[i] The University of Ottawa, Heart Institute, Diseases and Conditions; Inherited Cardiac Conditions (Genetic Disorders), 2018. https://www.ottawaheart.ca/heart-condition/inherited-cardiac-conditions-genetic-disorders
[ii] Mayo Clinic, Patient Care and Health Information; Diseases and Conditions; High Cholesterol, symptoms and causes. Aug 15, 2017. https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/symptoms-causes/syc-20350800.
iv British Heart Foundation, Information and Support, Heart Matters Magazine, Medical, Tests, Why should you have your cholesterol levels tested? Mike Knapton MD, Senior Cardiac Nurse Emily Reeve, 2018. https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/tests/blood-cholesterol?gclid=EAIaIQobChMI_uSd4PLQ3gIV7b3tCh2DawTiEAAYASAAEgLjdfD_BwE&gclsrc=aw.ds
[iv] British Heart Foundation, Information and Support, Heart Matters Magazine, Medical, Tests, Why should you have your cholesterol levels tested? Mike Knapton MD, Senior Cardiac Nurse Emily Reeve, 2018. https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/tests/blood-cholesterol?gclid=EAIaIQobChMI_uSd4PLQ3gIV7b3tCh2DawTiEAAYASAAEgLjdfD_BwE&gclsrc=aw.ds
[v] AIDS info, US department of health and science, Drug Information; Darunavir/ Brand name Prestiva ; Protease Inhibitor, last reviewed August 2018. https://aidsinfo.nih.gov/drugs/397/darunavir/0/patient.
[vi] NAM AIDSMAP Taking low-dose ritonavir with other protease inhibitors http://www.aidsmap.com/Taking-it/page/1731172/ Resources NAM publications 2018.
[vii] Echeverría P et al. Significant improvement in triglyceride levels after switching from ritonavir to cobicistat in suppressed HIV-1-infected subjects with dyslipidaemia. HIV Med. Online edition. DOI: 10.1111/hiv.12530 (2017).
[viii] Gatell, José M.et al Switching from a ritonavir-boosted protease inhibitor to a dolutegravir-based regimen for maintenance of HIV viral suppression in patients with high cardiovascular risk: CLINICAL SCIENCE: AIDS: November 28, 2017 - Volume 31 - Issue 18 - p 2503–2514 doi: 10.1097/QAD.0000000000001675
[x] Art Resnick MD, 2014, Kaiser Permanente Washington DC Website, 2018. https://wa.kaiserpermanente.org/healthAndWellness/index.jhtml?item=%2Fcommon%2FhealthAndWellness%2Fconditions%2FheartDisease%2FageAndGender.html
[xii] Pain, Rupert, MD, The University of Edinburgh, Cardiovascular Risk Calculator,2005, on line tool. http://cvrisk.mvm.ed.ac.uk/calculator/framingham.htm
[xiii] Wilson, Peter MD, Framingham Coronary Heart Disease Risk Score, 2005- 2018. MD+CAL https://www.mdcalc.com/framingham-coronary-heart-disease-risk-score
[xiv] NHS UK, BMI Healthy Weight Calculator, waist measurements 5/11/2018. https://www.nhs.uk/live-well/healthy-weight/bmi-calculator/
[xv] NHS UK, Physical activity guidelines for older people. 2018. https://www.nhs.uk/live-well/exercise/physical-activity-guidelines-older-adults/
[xvi] NHS UK, Eat well, Food Facts, Fat the facts.
[xvii] British Heart Foundation website 2018, Information and Support, Health and Emotional Support, Stress, Does Stress affect the heart. https://www.bhf.org.uk/informationsupport/support/health-and-emotional-support/stress
[xviii] D.J. Brotman, S.H. Golden, I.S. WittsteinThe cardiovascular toll of stress Lancet, 370 (2007), pp. 1089-1100
[xx] Are serious heart problems inevitable for people with HIV? A conversation with cardiologist Priscilla Hsue,
March 15, 2017, by San Francisco AIDS Foundation. https://betablog.org/heart-problems-hiv-cardiologist-priscilla-hsue/
[xxii] Islam FM, Wu J, Jansson J, Wilson DP. Relative risk of cardiovascular disease among people living with HIV: a systematic review and meta-analysis. HIV Med 2012;13:453-68.
[xxiii] Wiggins BS, Lamprecht DG, Page RL, Saseen JJ. Recommendations for managing drug-drug interactions with statins and HIV medications. Am J Cardiovasc Drugs 2017;17:375-89.