At the Heart of Longevity
Cardiovascular Health
A good head and a good heart are
always a formidable combination
Nelson Mandela
Founder of The Elders (www.theelders.org)
Peter Reiss
Director HIV Monitoring Foundation
Professor of Medicine
Department of Global Health &Division of Infectious Diseases
Amsterdam Institute for Global Health and Development
Academic Medical Center, University of Amsterdam
www.ias2013.org
Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Disclosures
• Unrestricted scientific grant support to my insitution for
investigator-initiated research fromGilead Sciences,
ViiV, Janssen Pharmaceutica, Merck and
Bristol Myers Squibb
• Honoraria paid to my institution for DSMB participation
and scientific advisory board participation from
Janssen Pharmaceutica and Gilead Sciences
www.ias2013.org
Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Case
• 52 year old man known with HIV for > 15 years.
• HIV well controlled with cART for 10+ years; CD4
450/mm3
• ART: history of long-term d4T use; currently on
TDF+3TC+EFV
• BMI 27 kg/m2; BP 150/100 mmHg; creatinine
clearance 55 ml/min
• Presents with increasingly frequent episodes of
chest pain
• Evaluation: Dx: angina pectoris as result of
coronary artery disease
www.ias2013.org
Kuala Lumpur, Malaysia , 30 June - 3 July 2013
What may be contributing to this
man’s coronary artery disease?
1.
2.
3.
4.
5.
6.
Being overweight
His HIV infection
His hypertension
His prior d4T use
His reduced renal function
Each of the above
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
INCIDENCE
Age-related chronic diseases
rise exponentially with age
Age
Age is the largest single risk factor
Cardiovascular
disease
Diabetes mellitus
Chronic liver disease
Non-Aids cancers
Frailty
Chronic obstructive
pulmonary disease
Osteoporosis &
Fragility fractures
Neurocognitive decline
Chronic kidney disease
Comorbidity in relation to age
Comorbidity distribution
*
Increased age-related
complications on ART
Mean AMI events per
1000 person years
6
5
5
3.9
4
3
2
3.3
2
2.2
1.5
1
0
40-49 years
50-59 years
HIV+
60-69 years
HIV-
Increased risk of AMI in HIV compared to HIV uninfected
HR = 1.48 (CI = 1.27 – 1.72)
Further increase HR if CD4<200 or HIV RNA>500
N=82,459; Veterans Ageing Cohort Study Virtual Cohort
Frieberg et al., JAMA Internal Med 2013
More Co-morbidity related to worse QoL
mean score on
physical funtioning
100
80
no co mo rbidity
60
1co mo rbidity
2 co mo rbidities
40
3 o r mo re co mo rb
20
0
hiv-infected
hiv-uninfected
Proportion reporting to be 100% unfit-to-work by
age category among working age cohort participants
% 40
30
45-50
51-55
20
56-60
61-65
10
0
hiv+
hiv-
HIV-positivity, older age and experiencing ≥ 3 age-associated
non-communicable co-morbidities, each were independently associated
with higher levels of non-participation in paid work
I. Stolte et. al. NCHIV 2012; Poster 46
Chronic disease drivers, known and suspected
 Many chronic diseases of ageing are more common in those
with HIV, even after adjustment for ART use and lifestyle
factors
ART
Toxicity
Persistent
Lifestyle Inflammation
(smoking etc.) in treated
HIV disease
Clinical
Chronic
Co-morbidity
Deeks SG, et al. BMJ 2009; 338:a3172
Representative 18F- FDG PET Images
Control
HIV
Axial
Image
F
Coronal
Image
S.Subramanian et al JAMA 2012;308:379-86
and S. Grinspoon CROI 2012
D:A:D: Changes in Causes of Death Over Time
1999-2011
 Proportion of deaths attributed to AIDS
fell over time
 Largely explained by increases in CD4+
cell counts
 Proportion of deaths attributed to nonAIDS causes increased over time
 non-AIDS ̶ defining malignancies now the
leading cause in this category
 Rate of death attributed to
cardiovascular or liver disease declined
over time
 possibly suggesting improved
management and care
 Rate of death attributed to non-AIDS
malignancy remained stable over time
Weber R, C. Smith et al. IAC2012. Abstract THAB0304.
32%
8%
10%
34%
1999-2000
(N = 255)
16%
AIDS related
CVD related
Other/unknown
Liver related
NADM
22%
2009-2011
(N = 548)
39%
9%
20%
AIDS related
CVD related
Other/unknown
10%
Liver-related
NADM
What advice would you give to our patient?
1.
2.
3.
4.
5.
Loose weight and exercise regularly
Stop smoking
Discontinue cART
Change current cART treatment
1. and 2 of the above
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
AgehIV Study Team
Academic Medical Center
HIV Monitoring Foundation
P. Reiss (PI)
F.W. Wit
M. van der Valk
J. Schouten
K. Kooij
B.C. Elsenga
A. Henderiks
F. de Wolf
S. Zaheri
Y.M. Ruijs
L. Gras
A. Kesselring
Public Health Service Amsterdam
M. Prins (co-PI)
I.G. Stolte
M. Martens
J. Berkel
S. Moll
A. van Roosmalen
G.R. Visser
Amsterdam Institute of Global Health
and Development
M. Heidenrijk
R. Meester
F. Janssen
Financial support:
The Netherlands Organisation for Health
Research and Development (ZonMW) grant
nr. 300020007 & Stichting AIDS Fonds grant
nr. 2009063
Additional unconditional grants from:
Gilead Sciences
ViiV Healthcare
Janssen Pharmaceuticals
Merck & Co
Bristol Myers Squibb