CV Risk in the Young. Dr. Susan Connolly Consultant Cardiologist Western Health and Social Care Trust

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1 CV Risk in the Young Dr. Susan Connolly Consultant Cardiologist Western Health and Social Care Trust

2 Hypertension Clinics Cardiology Clinics CV Risk Clinic Lipid Clinics Vascular Clinics Endocrinology Clinics Renal Clinics

hypertension Presented with NSTEMI and underwent PCI

3 Case 1 BC - 42 yo premenopausal female Non smoker, BMI 24 kg/m2 FHx premature CVD (father MI 39) No history hypertension Presented with NSTEMI and underwent PCI RCA Residual non obstructive atheroma in LAD and LCx Good LV

4 Follow up Attends clinic 4 weeks later Attending cardiac rehabilitation elsewhere Well but anxious Mother of 3 children 8, 11, 13 On rosuvastatin 40, DAPT, ramipril 1.25, bisoprolol 1.25 BP 125/75 mm Hg TC 4.2, HDL-c 1, Tg 1.1, LDL-c 2.7 mmol/l Hba1c 38

5 Question 1 What is the next test I order? Bubble echo Thrombophilia screen Lipoprotein (a) DNA sequencing for mutations in her LDL-R, ApoB and PCSK9 genes

6 Total cholesterol level greater than 7.5 mmol/l and/or a personal or family history of premature coronary heart disease (an event before 60 years in an index individual or first-degree relative) Total cholesterol >7.5 mmol/l and <30 years or Total cholesterol >9 mmol/l and >30 years Refer the person to an FH specialist service for DNA testing if they meet the Simon Broome criteria for possible or definite FH, or they have a DLCN score greater than 5 9

7 DNA diagnosis in relation to criteria score 2/3 children had mutation Now started on statins Haralambos et al. Atherosclerosis (1):190-6

8 Why is FH detection so important? Common and lethal 1:250 50% of men by 50 and 30% women by 60 will have developed CVD Putative prevalence of 20% in patients <50 with CHD Importance genetic testing Those with pathogenic variant higher CHD risk irrespective of LDL-c level Type of pathogenic variant predicts disease severity and attainment of LDL-c goals Autosomal dominant 1 st deg relatives 50% likelihood. LDL-c alone does not discriminate between carriers and non carriers. Cascade testing with DNA yields unambiguous results. Improves adherence with therapy Effective intervention and cost effective Recommended that statins started early in life ~ age 10 years. For every 1000 detected 100 MIs prevented. Estimated ICER 2,700 (well below NICE threshold 20,000)

8 million Why are detection rates in NI so high Regional FH Network in place Designated referral

9 Identification of FH in Northern Ireland (based on prevalence 1:500 and positive mutation detected) Population NI 1.8 million Why are detection rates in NI so high Regional FH Network in place Designated referral pathways from primary and secondary care 31% Specialist Lipid Clinics with Consultants and Lipid Nurses Active cascade screening Dedicated genetics laboratory (Belfast) <5%

10 Case 2 37 yo woman CM Previously well with no significant past medical history apart from asthma No family history of concern, current smoker, BMI 23 kg/m2 One week after NVD of a healthy boy (2nd pregnancy) and uneventful pregnancy) she developed recurrent episodes of right sided upper limb weakness, slurring of speech and right facial numbness. These episodes were transient lasting about 20 minutes each She was admitted to local obstetric hospital examination normal Normal FBC, U&E, LFT, CRP, TFTs, glucose, total cholesterol of 7.7, triglycerides of 8.08 and HDL of 0.89 mmol/l Normal ECG, ECHO and CT Brain

11 Investigations Duplex carotids MRI brain showed a left occipital cortex infarct and multiple small areas of ischaemic infarcts in her left frontal, parietal and occipital lobes Management Left carotid endarterectomy was performed Referred to CV Risk Clinic Lipo (a) normal Apo E genotyping performed E3/E3 Lifestyle modification Dual NRT High intensity statin therapy, ezetimibe, APT, Achieved non HDLc 2.4 mmol/l (originally 6.8) Duplex scan left internal carotid artery had a 50 to 69% plaque

12 Lipids in Pregnancy Supraphysiological dyslipidaemia association with Preclampsia Macrosomia Preterm birth IUGR Increased CVD risk mother and offspring Hong Shen et al. BMJ Open 2016;6:e013509

13 Secondary Dyslipidaemias

14 Question 2: Advice on further pregnancies 1. Yes 2. No

15 Case 3 A 17 yo South Asian girl referred by endocrinology for investigation of hypertension confirmed ABPM 164/89 mm Hg daytime average. Presented with a year s history of headaches, fatigue and significant weight loss No significant medical or family history. She did not smoke, drink alcohol, on no medication (including OCP and OTC). She had normal menses. She denied illicit drug use and excessive liquorice consumption. Examination: BMI 26/kg/m2, otherwise unremarkable

16 Case 3 Continued Normal FBC, U&E, LFTs, TFTs, bone, 24 urinary metanephrines normal Urine toxicology screen negative, negative pregnancy test Plasma aldosterone level 590 pmol/l ( pmol/l) Plasma renin activity 20 nmol/l/hr (0.3 to 3.1 pmol/ml/hr) and remained elevated on repeat Urine microscopy normal. Normal ACR 12 lead ECG normal ECHO normal (No LVH. Normal arch view) Renal US normal MRA renal arteries normal MR renal with mass protocol normal

17 What is most likely diagnosis? 1. Renal artery stenosis 2. Liddle s syndrome 3. Reninoma 4. Conn s syndrome

18 Renal angiography At outpatient follow up 6 weeks following the procedure her blood pressure was 102/72 mm Hg. Her plasma renin level now within the normal range at 0.6 nmol/l/h. Further MRA of head, neck chest vessels NAD

19 Fibromuscular dysplasia Idiopathic, non-inflammatory and non-atheroslerotic vascular disease (most commonly the renal, carotid and vertebral arteries) Typical beading appearance but it can present as a focal lesion. Causes not just stenosis but tortuousity, aneurysm and dissection Prevalence ~2.5%, higher in females, familial link, smoking, commonly multisite (1:2) Increasing appreciation of strong association of SCAD with FMD(25-86% cases) so head to pelvis screening recommend in both conditions

20 Case 4 AD: 47 yo premenopausal woman Referred by GP Dec 2018 with newly detected hypertension BP average 171/92 mm Hg in clinic (repeated measurement) Had presented with cellulitis toe Past Med Hx: investigated 2011 for palpitations on diltiazem since then No history UTIs No alcohol, no smoking, no drugs/liquorice/otc Runs regularly No FHx, No headaches, flushing, pallor, palpitations had mostly settled

21 Examination normal BMI 24 kg/m2 Normal FBC, U&E, LFTs, TFTs, HbA1c,bone profile 12 lead ECG normal ECHO: Mild concentric LVH, normal arch

22 Plasma metanephrines elevated Chromogranin A 8.1 ref range < 3.0 (nmol/l) NM MIBG IODINE 123 SPECT CT abnormal activity at lesion Admitted for commencement phenoxybenzamine Awaits surgical resection (laparoscopic adrenalectomy)

23 Resistant, Young <30/40, Disproprotionate TOD, Severe/accelerated/malignant Biochemical/clinical features e.g. low K+

24 Age Gradient and Secondary Hypertension

25 Clinical History 45 year old man Usually well Non smoker BMI 26.5 kg/m2 Normotensive TC 5, HDL-c 0.8, TG 1.1, LDLc 3.8 Lipo (a) normal Hba1c 42 mmol/mol No F/H of IHD Admitted with chest pain, ECG 1 st Degree HB, Troponin 0.12 (reference range ug/ml)

Represented to A&E 4 more times in subsequent 3 months with chest pain 2 more coronary angiograms similar to post PCI pictures Had declined CR due to work commitments Referred

27 Represented to A&E 4 more times in subsequent 3 months with chest pain 2 more coronary angiograms similar to post PCI pictures Had declined CR due to work commitments Referred CVD risk clinic Chest pain history reviewed - situational aspect Hospital anxiety and depression score 17/21 and 5/21 respectively Referred cardiac rehabilitation psychologist

Anxiety, CVD and Readmissions The Scream Edvard Munch UK National Audit Cardiac Rehabilitation 2018 1/3 patients have borderline or clinically significant anxiety levels at initial CR appointment

28 Anxiety, CVD and Readmissions The Scream Edvard Munch UK National Audit Cardiac Rehabilitation /3 patients have borderline or clinically significant anxiety levels at initial CR appointment (n=17,604) National SWEDEHEART registry Symptoms of emotional distress were prevalent in 38% and 33% at two and 12 months post MI respectively. Younger age one of key factors (n= 27,267 consecutive patients) Chest discomfort without myocardial infarction is the most common reason for early hospital readmission Nearly half of PCI readmissions are preventable Moretti et al Sixty-day readmission rate after percutaneous coronary intervention: predictors and impact on longterm outcomes. Eur Hear J Qual Outcomes. 2015; 1: Norlund et al. European Journal of Preventive Cardiology 2018, Vol. 25(9)

29 Safety Behaviours Is this a heart attack!? Checking heart Getting reassurance Stopping activity

Shift in beliefs re cause of chest pain 100 80 % Belief 60 40 20

30 Shift in beliefs re cause of chest pain % Belief Anxiety related Cardiac related 0 Feb March April May June Month

Ischaemic Heart Disease

Ischaemic Heart Disease Katherine Rothwell Case 1 65 yr old female PMHx : Eczema, is a smoker 20/day Comes to see you complaining of central chest pain Present past few months. Comes on when gardening