The cardiovascular challenge for primary care in diabetes Richard - PowerPoint PPT Presentation

The cardiovascular challenge for primary care in diabetes Richard Hobbs, Professor and Head Nuffield Department of Primary Care Health Sciences University of Oxford, United Kingdom

Is targeting cardiovascular disease prevention important?

Comparison of 10 leading diseases/injuries & leading risk factors on % deaths/DALYs k GBD 2010, Lancet 2013

Global Distribution of Mortality Attributed to 10 Leading CV Risk Factors Blood pressure Tobacco Lipids Underweight Unsafe sex Low fruit and vegetable intake High body mass index (BMI) Higher-mortality developing regions Physical inactivity Lower-mortality developing regions Alcohol Developed regions Unsafe water, S&H* 0 1 2 3 4 5 6 7 8 Attributable mortality in millions (total 55.9 million) * Sanitation and hygiene The World Health Report 2002: reducing risks, promoting healthy life. Geneva, Switzerland: World Health Organization; 2002

Prevalence of diabetes in 2030 2 0 1 0 2 0 3 0 Total number of people 285 million 438 million with diabetes (age 20-79) Prevalence of diabetes 6.6 % 7.8 % (age 20-79) IDF diabetes atlas, 4th edition, 2009

Diabetes doubles the risk of vascular disease Data from 102 prospective studies, 530,083 participants (adjusted for age sex, cohort, SBP, smoking, BMI) Outcome I 2 (95% CI) Number HR (95% CI) of cases Coronary heart disease 26 505 2.00 (1.83 - 2.19) 64 (54-71) Coronary death 11 556 2.31 (2.05 - 2.60) 41 (24-54) Non-fatal myocardial 14 741 1.82 (1.64 - 2.03) 37 (19-51) infarction Cerebrovascular disease 11 176 1.82 (1.65 - 2.01) 42 (25-55) Ischaemic stroke 3799 1 (0-20) 2.27 (1.95 - 2.65) Haemorrhagic stroke 1183 1.56 (1.19 - 2.05) 0 (0-26) Unclassified stroke 4973 1.84 (1.59 - 2.13) 33 (12-48) Other vascular deaths 3826 1.73 (1.51 - 1.98) 0 (0-26) 1 2 4 Hazard ratio (diabetes vs. no diabetes) Emerging Risk Factors Collab. Lancet. 2010 Jun 26;375(9733):2215-22

Type 2 diabetes increases CVD risk over time CHD equivalence threshold CHD risk ~10 years’ Diagnosis duration Age • CVD/CHD risk at or prior to diagnosis is determined by conventional CHD risk factors • Hyperglycaemia in the diabetic range increases CHD risk over time • After a diabetes duration of >10 years CHD risk equivalence is reached Sattar N. Diabetologia 2013;56:686-695 .

Diabetes associated with significant loss of life years Men Women 7 7 Non-vascular deaths 6 6 Vascular deaths 5 5 Years of life lost 4 4 3 3 2 2 1 1 0 0 0 40 50 60 70 80 90 0 40 50 60 70 80 90 Age (year) Age (year) On average, a 50-year old with diabetes but no history of vascular disease is ~6 years younger at time of death than a counterpart without diabetes 9 Seshasai et al. N Engl J Med 2011;364:829-41.

Managing CV risk beyond glucose control

Smoking Hazards & Cessation Benefits 113,752 w and 88,496 m aged ≥ 25y in US NHIS Jha N Engl J Med 2013; 368: 341-50

Blood pressure modification in diabetes

Results of randomised trials of antihypertensive drug therapy Heart Fatal/Nonfatal Fatal/Nonfatal Vascular failure stroke CHD deaths 0 -16% -10 -21% -20 -30 -38% -40 -52% -50 BP CTC, Collins R et al Lancet 1990 Risk reduction (%) 17 trials, 47 653 patients, SBP diff 10-12 mm Hg, DBP diff 5-6 mm Hg Moser & Herbert J Am Coll Cardiol 1996

Similar proportional reductions in risk with BP lowering in diabetes as non-diabetes BP treatment Trialists. Arch Int Med 2005, 165, 1410-1419

Lipid modification in diabetes

Statin vs control: Proportional effects on major vascular events per mmol/L LDL-C reduction (26 Trials, 170,000 Subjects) Relative risk (CI) per No. of events (% pa) Statin Control mmol/L LDL-C reduction 2310 (0.9%) 3213 (1.2%) 0.74 (0.69 - 0.78) Nonfatal MI 1242 (0.5%) 1587 (0.6%) 0.80 (0.73 - 0.86) CHD death Any major coronary event 3380 (1.3%) 4539 (1.7%) 0.76 (0.73 - 0.79) 816 (0.3%) 1126 (0.4%) 0.76 (0.69 - 0.83) CABG 601 (0.2%) 775 (0.3%) 0.78 (0.69 - 0.89) PTCA Unspecified 1686 (0.6%) 2165 (0.8%) 0.76 (0.70 - 0.83) Any coronary revascularisation 3103 (1.2%) 4066 (1.6%) 0.76 (0.73 - 0.80) 987 (0.4%) 1225 (0.5%) 0.80 (0.73 - 0.88) Ischaemic stroke Haemorrhagic stroke 188 (0.1%) 163 (0.1%) 1.10 (0.86 - 1.42) 555 (0.2%) 629 (0.2%) 0.88 (0.76 - 1.02) Unknown stroke Any stroke 1730 (0.7%) 2017 (0.8%) 0.85 (0.80 - 0.90) Any major vascular event 7136 (2.8%) 8934 (3.6%) 0.79 (0.77 - 0.81) 0.4 0.6 0.8 1 1.2 1.4 99% or 95% CI Statin better Control better CTT2. Lancet 2010;376:1670–81

Statins – similar reductions in CV events in diabetes versus non diabetes (per 1 mmol/L or 39mg/dl lower LDL-C) CTT Lancet 2 0 0 8 , 3 7 1 , 1 1 7 -2 5

Statins increase risk of dysglycaemia Sattar N et al. Lancet. 2010;375:735-42.

Residual risk despite lipid therapy: CVD events incidence according to level of CV risk among adherent and nonadherent patients. Clinicoecon Outcomes Res. 2016; 8: 649-55.

Glycaemia control

No evidence from prospective trials that more intensive glycaemic control reduces mortality Meta-analysis including 27,049 participants and 2370 major vascular events Number of events (annual event rate, %) Favours less Favours more ∆HbA 1c (%) Trials More intensive Less intensive intensive intensive All-cause mortality ACCORD 257 (1.41) 203 (1.14) -1.01 ADVANCE 498 (1.86) 533 (1.99) -0.72 UKPDS 123 (0.13) 53 (0.25) -0.66 Overall HR (95% CI) VADT 102 (2.22) 95 (2.06) -1.16 Overall 980 884 -0.88 1.04 (0.90–1.20) Cardiovascular death ACCORD 137 (0.79) 94 (0.56) -1.01 ADVANCE 253 (0.95) 289 (1.08) -0.72 UKPDS 71 (0.53) 29 (0.52) -0.66 VADT 38 (0.83) 29 (0.63) -1.16 1.10 (0.84–1.42) Overall 497 441 -0.88 0.5 1.0 2.0 Hazard ratio (95% CI) Turnbull et al. Diabetologia 2009;52:2288–98. 21

Modest benefit of intensive glycaemic control on macrovascular risk Meta-analysis including 27,049 participants and 2370 major vascular events Number of events (annual event rate, %) Favours more Favours less Trials More intensive Less intensive ΔHbA 1c (%) intensive intensive Major cardiovascular events * ACCORD 352 (2.11) 371 (2.29) -1.01 ADVANCE 557 (2.15) 590 (2.28) -0.72 UKPDS 169 (1.30) 87 (1.60) -0.66 VADT 116 (2.68) 128 (2.98) -1.16 Overall HR (95% CI) † Overall 1194 1176 -0.88 0.91 (0.84–0.99) Stroke Overall 378 370 -0.88 0.96 (0.83–1.10) Myocardial infarction 0.85 (0.76–0.94) Overall 730 745 -0.88 Hospitalised/fatal heart failure 1.00 (0.86–1.16) Overall 459 446 -0.88 0.5 1.0 2.0 *Major CV events = CV death or non-fatal stroke or non-fatal MI. Hazard ratio (95% CI) †Diamonds incorporate point estimate (vertical dashed line) and encompass 95% CI of overall effect for each outcome. Turnbull et al. Diabetologia 2009;52:2288–98. 22

Lifestyle modification

Lifestyle vs Metformin vs placebo Diabetes Prevention Program - 31% Parallel - 58% DPP : N Engl J Med 2002; 346: 393-403 .

Pooled estimates of effects of lifestyle intervention -50% BMJ 2007

Is the impact of diabetes on primary care likely to change? Predicted trends in diabetes

8 AdultBMIstatusby sex Health Survey for England 2012 to 2014 (three-year average) Underweight Underweight 1.6% 1.9% Obese Obese 24.9% 25.2% Healthy/weight 32.0% Men Women Healthy/weight 40.6% Overweight Overweight 32.3% 41.5% Adult (aged 16+) BMI thresholds: Underweight: <18.5kg/m 2 Overweight: 25 to <30kg/m 2 Healthy weight: 18.5 to <25kg/m 2 Obese: ≥30kg/m 2 Patterns and trends in adult obesity

Trendin obesityprevalenceamongadults Health Survey for England 1993 to 2014 (three-year average) 30% Women Men 25% 20% Prevalence)of)obe 15% sity 10% 5% 0% Adult (aged 16+) obesity: BMI ≥ 30kg/m 2 Patterns and trends in adult obesity

Relative Risk for type 2 diabetes 84,941 nurses: 16 years follow-up 40 Relative risk of type 2 38.8 30 diabetes 20 20.1 10 7.6 1.0 0 15 20 25 30 35 40 Body mass index Hu FB. N Engl J Med. 2001; 345:790-7.

Age-Adjusted Prevalence of Obesity and Diagnosed Diabetes Among U.S. Adults Aged 18 Years or older Obesity (BMI ≥ 30 kg/m 2 ) 2010 1994 2000 No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0% Diabetes 2010 1994 2000 No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0% CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http:// www.cdc.gov/diabetes/statistics

Conclusions for primary care? • CVD are the world’s most important NCDs – Premature and total mortality – Rates of disability and healthcare spend • CVD risk is accelerated in diabetes – Traditional risk factors remain important in diabetes – Very large evidence base on these risk interventions • CV risk management in diabetes ⎼ Limited evidence for glucose reduction & reduced CVD ⎼ Despite evidence for main CV risk factors, high residual risk • Diabetes & CVD risk rapidly increasing in most countries – Reducing obesity is critical – Maximise traditional CV risk reduction – Need novel CVD interventions, especially in diabetes