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?

GBD 2010, Lancet 2013

Comparison of 10 leading diseases/injuries & leading risk factors on % deaths/DALYsk

Global Distribution of Mortality Attributed to 10 Leading CV Risk Factors

Attributable mortality in millions (total 55.9 million)

Blood pressure Tobacco Lipids Underweight Unsafe sex Low fruit and vegetable intake High body mass index (BMI) Physical inactivity Alcohol Unsafe water, S&H*

1 2 3 4 5 6 7 8

Higher-mortality developing regions Lower-mortality developing regions Developed regions

The World Health Report 2002: reducing risks, promoting healthy life. Geneva, Switzerland: World Health Organization; 2002 * Sanitation and hygiene

IDF diabetes atlas, 4th edition, 2009

2 0 1 0 2 0 3 0 Total number of people with diabetes (age 20-79) 285 million 438 million Prevalence of diabetes (age 20-79) 6.6 % 7.8 %

Prevalence of diabetes in 2030

Coronary heart disease Coronary death Non-fatal myocardial infarction Cerebrovascular disease Ischaemic stroke Haemorrhagic stroke Unclassified stroke Other vascular deaths 2.00 (1.83 - 2.19) 2.31 (2.05 - 2.60) 1.82 (1.64 - 2.03) 1.82 (1.65 - 2.01) 2.27 (1.95 - 2.65) 1.56 (1.19 - 2.05) 1.84 (1.59 - 2.13) 1.73 (1.51 - 1.98) HR (95% CI) 26 505 11 556 14 741 11 176 3799 1183 4973 3826 Number

• f cases

64 (54-71) 41 (24-54) 37 (19-51) 42 (25-55) 1 (0-20) 0 (0-26) 33 (12-48) 0 (0-26) I2 (95% CI) 1 2 4 Hazard ratio (diabetes vs. no diabetes) Outcome

Emerging Risk Factors Collab. Lancet. 2010 Jun 26;375(9733):2215-22

Diabetes doubles the risk of vascular disease

Data from 102 prospective studies, 530,083 participants (adjusted for age sex, cohort, SBP, smoking, BMI)

Type 2 diabetes increases CVD risk

• ver time
• 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.

CHD risk Age Diagnosis ~10 years’ duration CHD equivalence threshold

Diabetes associated with significant loss of life years

9

Seshasai et al. N Engl J Med 2011;364:829-41.

7 6 5 4 3 2 1 40 50 60 70 80 90 Age (year) Years of life lost

Men

7 6 5 4 3 2 1 40 50 60 70 80 90 Age (year)

Women

Non-vascular deaths Vascular deaths

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

Managing CV risk beyond glucose control

Jha N Engl J Med 2013; 368: 341-50

Smoking Hazards & Cessation Benefits

113,752 w and 88,496 m aged ≥25y in US NHIS

Blood pressure modification in diabetes

Results of randomised trials of antihypertensive drug therapy

• 50
• 40
• 30
• 20
• 10

Heart failure Fatal/Nonfatal stroke Fatal/Nonfatal CHD Risk reduction (%)

BP CTC, Collins R et al Lancet 1990 17 trials, 47 653 patients, SBP diff 10-12 mm Hg, DBP diff 5-6 mm Hg Moser & Herbert J Am Coll Cardiol 1996

Vascular deaths

• 52%
• 38%
• 16%
• 21%

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

0.4 0.6 0.8 1 1.2 1.4 Nonfatal MI CHD death Any major coronary event CABG PTCA Unspecified Any coronary revascularisation Ischaemic stroke Haemorrhagic stroke Unknown stroke Any stroke Any major vascular event 2310 (0.9%) 1242 (0.5%) 3380 (1.3%) 816 (0.3%) 601 (0.2%) 1686 (0.6%) 3103 (1.2%) 987 (0.4%) 188 (0.1%) 555 (0.2%) 1730 (0.7%) 7136 (2.8%) 3213 (1.2%) 1587 (0.6%) 4539 (1.7%) 1126 (0.4%) 775 (0.3%) 2165 (0.8%) 4066 (1.6%) 1225 (0.5%) 163 (0.1%) 629 (0.2%) 2017 (0.8%) 8934 (3.6%) 0.74 (0.69 - 0.78) 0.80 (0.73 - 0.86) 0.76 (0.73 - 0.79) 0.76 (0.69 - 0.83) 0.78 (0.69 - 0.89) 0.76 (0.70 - 0.83) 0.76 (0.73 - 0.80) 0.80 (0.73 - 0.88) 1.10 (0.86 - 1.42) 0.88 (0.76 - 1.02) 0.85 (0.80 - 0.90) 0.79 (0.77 - 0.81)

Statin vs control: Proportional effects on major vascular events per mmol/L LDL-C reduction

(26 Trials, 170,000 Subjects)

• No. of events (% pa)

Statin Control Relative risk (CI) per mmol/L LDL-C reduction

Statin better Control better

99% or 95% CI

• 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

21

Turnbull et al. Diabetologia 2009;52:2288–98.

Meta-analysis including 27,049 participants and 2370 major vascular events

0.5 1.0 2.0 Hazard ratio (95% CI) 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

VADT 102 (2.22) 95 (2.06)

• 1.16

Overall 980 884

• 0.88

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

Overall 497 441

• 0.88

All-cause mortality Cardiovascular death Trials Number of events (annual event rate, %) More intensive Less intensive ∆HbA1c (%) Favours more intensive Favours less intensive Overall HR (95% CI) 1.04 (0.90–1.20) 1.10 (0.84–1.42)

Trials Number of events (annual event rate, %) ΔHbA1c (%) Favours more intensive Favours less intensive More intensive Less 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 1194 1176

• 0.88

Stroke Overall 378 370

• 0.88

Myocardial infarction Overall 730 745

• 0.88

Hospitalised/fatal heart failure Overall 459 446

• 0.88

Meta-analysis including 27,049 participants and 2370 major vascular events

Modest benefit of intensive glycaemic control

• n macrovascular risk

22

*Major CV events = CV death or non-fatal stroke or non-fatal MI. †Diamonds incorporate point estimate (vertical dashed line) and encompass 95% CI of overall effect for each

• utcome.

Turnbull et al. Diabetologia 2009;52:2288–98.

1.0 0.5 2.0 Hazard ratio (95% CI)

†

Overall HR (95% CI) 0.91 (0.84–0.99) 0.96 (0.83–1.10) 0.85 (0.76–0.94) 1.00 (0.86–1.16)

Lifestyle modification

Lifestyle vs Metformin vs placebo

DPP : N Engl J Med 2002; 346: 393-403.

Diabetes Prevention Program

• 58%
• 31%

Parallel

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

Adult (aged 16+) BMI thresholds: Underweight: <18.5kg/m2 Overweight: 25 to <30kg/m2

Underweight

1.6%

Healthy/weight

32.0%

Overweight 41.5% Obese

24.9%

Men

Underweight

1.9% Healthy weight: 18.5 to <25kg/m2 Obese: ≥30kg/m2

8

Patterns and trends in adult obesity

Healthy/weight

40.6%

Overweight

32.3%

Obese

25.2%

Women

AdultBMIstatusby sex

Health Survey for England 2012 to 2014 (three-year average)

Prevalence)of)obe sity 30% Women Men 25% 20% 15% 10% 5% 0% Adult (aged 16+) obesity: BMI ≥ 30kg/m2 Patterns and trends in adult obesity

Trendin obesityprevalenceamongadults

Health Survey for England 1993 to 2014 (three-year average)

Relative risk of type 2 diabetes

Relative Risk for type 2 diabetes 84,941 nurses: 16 years follow-up

10 20 30 40

15

38.8 20.1 7.6 1.0

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

Diabetes Obesity (BMI ≥30 kg/m2) 1994 1994 2000 2000

No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0%

2010 2010

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