Cardiology research 25 july 2020

Madam Curie Foundation
(A Registered Charitable Trust)
https://madamcuriefoundation.wordpress.com
CME Program 25th July 2020
DR. R. H. JANI
JANIRH@GMAIL.COM
25-07-2020DR. R. H. JANI, E-MAIL - JANIRH@GMAIL.COM 1

Inspiration
We must believe that we are gifted for something, and that this thing, at whatever
cost, must be attained.
Madam Marie Curie

Madam Curie:
 Madam Curie Foundation is inspired by the life and work of a research scientist, Marie Curie, who
was not only a great scientist with two Nobel Prices, but crusader better humanitarian world.
 Madam Marie Curie was born on November 7, 1867.
 She was the first person and fist woman to win two Nobel Prizes, in Physics, and later in Chemistry,
 Her efforts with her husband Pierre resulted into the discovery of polonium and radium.
 She championed the development of X-rays.
 During World War I in 1914, she devoted her time and resources to the cause of war victims. She
championed the use of portable X-ray machines in the field, and these medical vehicles earned
the nickname “Little Curies.”
 She died on July 4, 1934, of aplastic anemia, believed to be caused by prolonged exposure to
radiation.

Madam Curie Foundation is a registered charitable trust and is settled by Dr. Rajendra
Jani, a medical researcher and philanthropist. The Foundation works in the fields of
healthcare, research, education, skill development, and community development.
http://madamcuriefoundation.wordpress.com

 Our Activities:
 Healthcare Service and Research
 Medical Relief
 Healthcare research
 Advisory support to healthcare startups
 Education and skill development programs
 Research Methodology
 Infection Control and prevention
 Good Clinical Practices
 Community health education
 Empowerment to underprivileged

Past, Present and Future of Research in Cardiology
Continuous Medical Education
DR. R. H. JANI
JANIRH@GMAIL.COM

Cardiology Research : 8th Century BC to 2nd Century AD
 In 8th Century BC, in The Iliad, the earliest record of the heart comes.
 Homer compiled anatomical descriptions of exposed organs on the Trojan battlefield
 Fibrinous pericarditis is recorded The Iliad (doi:10.1183/09031936.94.07122234)
 The earliest Cardiology research was anatomical dissection:
 Herophilos (335-280 BC) was the first to (legally) dissect human cadavers, and postulated that its the brain, not the
heart, as Aristotle had thought, was the ‘seat of intelligence
 Galen (129-216 AD) substantially advanced heart research and showed that arteries contain blood not air
 Many inaccuracies existed in Galen research such as
 blood moves from the heart in an ebb-and-flow motion rather than by circulation
 blood passed from the right to the left ventricle of the heart through invisible holes in the septum.
 Galen’s ideas continued unchallenged for a long time, from the 2nd to 16th Century due to the control of religion over
the research

Cardiology Research : 2nd to 17th Century AD
 Abu-Marwan Abdel-Malik Ibn Zuhr (Avenzoar, 1093-1162 AD) demonstrated the
feasibility of safe operations in humans, by performing surgery on goats,
 Muhadhdhab Al-Deen Al-Baghdadi (1117-1213 AD), developed clinical practice in
and stressed the need of history taking, physical examination, diagnosis and
prognosis
 Leonardo da Vinci (1452-1519) studied physiology, and described
 First time accurate drawings of the internal functioning of the heart in Quaderni di Anatomia,
vol 2; folio 3v
 heart as a muscle and the atria are chambers, and
 the first to document atherosclerotic coronary arteries.

Cardiology Research : 2nd to 17th Century AD
 William Harvey, was a forefather of modern research practices,
 Emphasized the need of testing a hypothesis by observable, repetitive and rationally designed
experiments.
 He published crucial research, On the Motion of the Heart and Blood in Animals.

Cardiology Research : The recent past - 18th and 19th century
 The study of anatomy flourished in the 18th and 19th centuries, and more widespread
use of the printing press following its introduction in the 16th Century facilitated
publication and exchange of ideas.
 In 1832, the Anatomy Act was passed by parliament in the UK, legalizing use of studies
on unclaimed or donated human cadavers. As a result of this, the still authoritative text
Gray’s Anatomy,came into existence
 The immense contribution that animal research has made to progress in heart research
followed by laws on use of animals in the UK
 1822: the first animal protection laws,
 1876: the Cruelty to Animals Act,
 1986: the Animals (Scientific Procedures) Act was introduced to regulate the use of animals used for
research in the UK,and is continually revised to this day..

Eugene Braunwald JACC 2003;42:2031-2041
American College of Cardiology Foundation
Cardiology Research : Electrocardiography
The 20th century
 Willem Einthoven (1903) : The birth of
modern cardiology can be dated to one
century ago, when he
 First recorded a human electrocardiogram
and gave birth to a new specialty.
 He devised the first-string galvanometer to
record the electrical activity of the heart
 This was instrumental in the development
of mechanical devices that aim to restore
normal electrophysiological properties of
the heart such as pacemakers and
Implanted Cardioverter Defibrillators (ICDs)
 Einthoven was appropriately rewarded with
a Nobel Prize in medicine.

Cardiology Research : Echocardiography
The 20th century
 1952: Inge Edler, a Swedish cardiologist, and Helmuth
Hertz, a Swedish physicist collaborated.
 They adapted for human use a sonar device for
detecting submarines in World War II and recorded
echoes from the walls of the heart of one of the
coinventors, “Hertz' heart,” and thereby launched the
field of echocardiography.
 These investigators provided continuous recordings of
the movements of the heart walls and of the normal and
diseased mitral valve.
 The visualization of the heart and great vessels by
noninvasive imaging, first by echocardiography and
subsequently by a variety of nuclear techniques, as
well as by advanced radiologic techniques (computed
tomography and magnetic resonance imaging) now
makes many invasive diagnostic procedures
unnecessary.
Helmuth Hertz (left)and Inge Edler (right)with the first
echocardiograph.

Eugene Braunwald JACC 2003;42:2031-2041
American College of Cardiology Foundation
Forssman ( Fig A), Cournand Fig B), and Richards were also
awarded the Nobel Prize for catheterization
Cardiology Research : Cardiac catheterization
The 20th century
 1929: Werner Forssman (Fig. A)
 The first catheterization of the living human
heart was performed by a young surgeon (on
himself!) in Germany to find a safe way to inject
drugs and contrast material into the right atrium
for cardiac resuscitation
 1941: Andre Cournand (Fig. B) and
Dickinson Richards at Columbia University
and Bellevue Hospital in New York
 recorded intracardiac pressures and cardiac
output in normal subjects and in patients with
many forms of congenital and acquired heart
disease.

Cardiology Research : Coronary angiography
The 20th century
 1958: Mason Sones (Fig. A) at the
Cleveland Clinic Cardiac first time
conducted coronary arteriography
 1961, Desmond Julian (Fig. C), from
cardiology at the Royal Infirmary in
Edinburgh, Scotland, articulated the
concept of the coronary care unit
 1977: Andreas Gruentzig (Fig. B),
Developed percutaneous transluminal
coronary angioplasty, and established
a new subspecialty: interventional
cardiology.

Cardiology Research : Cardiovascular drugs
The 20th century
 1960s: James Black from ICI developed beta-blockers and was honored for this and other
discoveries with the Nobel Prize.
 These remarkable agents have benefited patients with acute and chronic myocardial ischemia, heart failure,
a variety of arrhythmias, and hypertension.
 1970s: Cushman and Ondetti, working at the Squibb (now Bristol Myers Squibb) laboratories
isolated the first angiotensin-converting enzyme inhibitor (ACE), captopril.
 ACE inhibitors have become cornerstones in the management of heart failure and hypertension.
 1976: Akira Endo of Sankyo Pharmaceuticals discovered, the first HMG-CoA reductase inhibitor
(statin)
 It was built on the Nobel Prize-winning work on the low density lipoprotein cholesterol pathway by Brown and
Goldstein.
 Statins reduce substantially the incidence of coronary events, and prolong life both in subjects with and without
hypercholesterolemia. Taken together, beta-blockers, angiotensin-converting enzyme inhibitors, and statins have
prolonged and improved the lives of tens, perhaps hundreds, of millions of patients worldwide.

Cardiology Research : Pacemakers and internal defibrillators
The 20th century
 1952: Paul Zoll, a cardiologist at Harvard and Beth Israel Hospital, developed the
first external pacemaker and,
 1959: Elmquist and Senning at the University of Zurich reported on the first
successful use of an internal pacemaker.
 1970: Michel Mirowski, an Israeli cardiologist with training in electrical engineering
working at Sinai Hospital in Baltimore, invented the implanted cardioverter-
defibrillator, and a decade later reported on its successful clinical application.
 A steady drumbeat of successful clinical trials has greatly extended the indications for this
important device, both in the secondary and primary prevention of sudden cardiac death.
(https://www.onlinejacc.org/content/42/12/2031 Accessed pn 21st July 2020 at 11:29am IST)

Cardiology Research : Preventive cardiology
The 20th century
 1944: Dr. Paul Dudley White at Harvard and the Massachusetts General Hospital, often
referred to as the father of American cardiology, pioneered the concept of cardiovascular
prevention.
 1948: Framingham Heart Study was established the National Heart Institute (now the
National Heart, Lung, and Blood Institute)
 the first prospective population-based cohort study that focused on heart disease.
 1961: Kannel et al. had identified hypertension, smoking, and electrocardiographic evidence of left
ventricular hypertrophy as such risk factors.
 Based on these (and other subsequently identified) risk factors, the primary and secondary
prevention of coronary artery disease has been responsible for almost one-half of the dramatic 70%
decline in age-adjusted deaths from coronary artery disease that has occurred since their
publication.

Cardiology Research : Lessons from past great achievement
The 20th century
 (1) these achievements did not develop de novo;
 they were built on many decades of research, usually by basic scientists and engineers, the unsung
heroes of progress in cardiology.
 (2) In almost every instance, these advances came from
 interdisciplinary collaborations, such as between a cardiologist and physicist in the case of
echocardiography, or
 between epidemiologists and cardiologists in the Framingham Heart Study.
 Successful collaboration between academia and industry has also been vital to many of these advances.
Examples are the first heart-lung machine and cardiac drugs, as well as catheters and electrical devices.
 (3) these great achievements are international triumphs;
 investigators in many countries across the globe are among discussed.
 Countless others from dozens of nations have contributed importantly to contemporary cardiology.

Cardiology Research: Future
 Past:
 Somebody would come in with a heart attack and all we could do was give them a painkiller,
put them in a bed and watch them either recover or die.
 Now:
 We understand cardiovascular diseases much better and have extended survival of patients
much longer
 Future:
 The challenges are how to make lives of patients live! liveable?
 What shall we do to do to prevent cardiovascular diseases?

 What are some of the remaining challenges?
 The number of people surviving a heart attack, or two or three heart attacks has increased but as a
result of surviving those heart attacks they now have very badly damaged hearts. They live with
heart failure, which is miserable. Drugs, which we’ve helped trial, which help improve the outcome
for people with heart failure but it’s still a very devastating condition.
 We try to understand how to repair a damaged heart in the hope that in the next few years, there
will be new treatments for people with badly damaged hearts that could reduce their heart failure.

What are some of the promising domain in research?
Devices
Electronic
Mechanical
ICDs: Implantable Cardiovert
Defibrillator
S-ICDs: Subcutaneous ICDs
Others:
Genomics and Pharmacogenetics-
Repurposing of therapeutic Options
Bioinformatics
CVRG: Cardio Vascular Research
Grid
Cell Rx
Skeleton Muscles
Bone Marrow Stem Cells
Xenotransplant

 Heart failure is the last great battleground in cardiology.
 There is the ominous increase in the number of annual discharges of heart failure patients from
hospitals.
 In the near-term future the management of heart failure is likely to advance along three paths:
 A expansion and broadening of the indications for electrical device therapy such as cardiac
resynchronization and implanted cardiac cardioversion and defibrillation.
 Innovative efforts are underway to coax the failing heart to recover following the removal of a left
ventricular assist device in so-called “bridge to recovery” therapy.
 Cell therapy represents a very promising approach. Two modes are now under active investigation: the
injection of cultured autologous myoblasts and the use of autologous bone marrow-derived stem cells.
 For patients with acute severe heart failure, mechanical ventricular assistance is likely to be employed
as bridging therapy while cell therapy regenerates the heart. Cardiac xenotransplantation might
become a reality, and this could change drastically the entire landscape of the management of severe
heart failure.

 Genetics and pharmacogenomics are a very promising area of science.
 Fatal conditions dictated by single gene defects - already under attention and partially address (see below)
 Fata conditions dicted by polygene defect – need attention

Genome Wide Association (GWAS) Studies
 Recent genome-wide association studies (GWAS) have identified multiple loci
associated with coronary artery disease (CAD) among predominantly Europeans.
 missense SNP in the APOA5 (Apolipoprotein A5) gene, rs2075291, was found to
be associated with CAD at a level of genome-wide significance in multi-ethnic
cohorts from Southeast Asia comprising subjects of Chinese, Malay and Asian
Indian ancestry

 Genomics
 Large scale genome sequencing hastened the discovery of gene variants which confer
risk for many common and complex diseases.
 A number of discoveries have been made in cardiovascular medicine of sequence
variants which are associated with disorders such as
 coronary artery disease, atrial fibrillation, peripheral vascular disease, aortic aneurysm and ischemic
stroke.
 Polymorphic genetic variants associated with a risk for different diseases creates an
opportunity for predictive and preventive medicine.
 Clinical laboratories offer studies of over 30,000 variants associated with genetic
susceptibility, which are ever more accessible to physicians and patients.

 At present, existing criteria for diagnosis therapeutic management are like age,
body mass index, complete blood count or kidney function, etc. and are
predominantly phenotypic.
 The individual genetic features of patients and their diseases are largely
neglected.
 It is now more relevant than any other time to
 understand and improve patient care using knowledge of genetic polymorphisms.
 improve the characterization of prevalent and incident cardiovascular diseases;
 Select suitable treatment, as well as to determine the appropriate medications and doses for
each patient.

 Impact of genomics on our daily life-
 Legal aspects:
 Prescribing information of medicine started listing the difference in response according to patients’ genetic
variations. This will make physicians to responsible for verification of pharmacology polymorphisms before
prescribing a medicine, dose, dosage schedules, concomitant medication, etc.
 Genetic counselling:
 Presence recessive diseases in parents, where two recessive allele of mutated gene, may be expressed in
children as a disease.
 Physician will be required to advice for preimplantation or adaptation of a child.
 Insurance companies will use genetic profiling for reducing the cost of adverse events

Recent applications of Mendelian randomization studies
 Repurposing drugs
 Mendelian randomization can be used to inform on potential repurposing of drugs, for example
through use of a ‘phenome-wide scan’, which is facilitated by the availability of large-scale
prospective biobanks with incident diagnoses procured through electronic health records,
 Taking the example above of Lp-PLA2 in the creatine kinase B (CKB), there was no evidence of an
association of genetic variants in V279F with risks of other diseases.
 While this supports safety data from clinical trials of darapladib, an inhibitor lipoprotein-associated
phospholipase A2 (Lp-PLA2) for treatment of atherosclerosis,
25 March 2018RAJENDRA JANI, GENOMICS OF CARDIOMETABOLICS 29

 Clinical trial Design : Mandelman Randomization
 Predicting efficacy
 The efficacy of potential therapeutic targets as early as possible in the drug development
process, as genetic support for a drug target can substantially enhance the probability
that a RCT of a therapy targeting such a drug target succeeds.
 Predicting target-mediated adverse effects
 As an examples recent Mendelian randomization studies have provided orthogonal
evidence that LDL-C lowering through PCSK9 inhibition is, as with statins, likely to lead to
increased risk of T2D, and more generally, a recent study using SNPs across the genome
provides evidence that an increased risk of T2D may arise as a general consequence of
LDL-C lowering.

Mendelian randomization studies in cardiometabolic diseases
Exposure Outcome Interpretation Importance Refs
LDL
cholesterol
CHD Dose–response
relationship
irrespective of locus
Suggests LDL-cholesterol lowering by any means is beneficial,
consistentwith trialsinvolvingstatinand other
cholesterol- lowering interventions
1
HDL
cholesterol
CHD No causal effect Contradictsobservational data, but supports findingsfrom
recent RCTs
2-4
Triglycerides CHD Causal Precedes trial data of a triglyceride-lowering agent 2, 4, 5
sPLA2-IIA CHD Noncausal Published at a similar time to the VISTA-16 trial of a sPLA2-
IIA-lowering drug that did not have beneficial effects on CVD
32
Lp-PLA2 CHD Noncausal Many resourceswere spenton trials thatshowed therapeutic
lowering of Lp-PLA2 level does not lower risk of CVD; some MR
studieswere publishedbefore the reportingof RCT results
6,7,8, 9
NPC1L1/
ezetimibe
CHD Causal MR studiespreceded RCT data, that showed lowering of LDL-
cholesterol level via inhibition of NPC1L1 results in reduced
risk of CVD
10,11
PCSK9,
lipoprotein(a),
and ANGPTL4
CHD Causal Drugs developed for CVD prevention on basis of genetic
findings, some of which have since shown cardiovascular
benefit in phase III RCTs
12-14

Mendelian randomization studies in cardiometabolic diseases
Exposure Outcome Interpretation Importance Refs
BMI Metabolites BMI causally influences
many circulating
metabolites
Supports the interpretationthat BMI might influence
cardiometabolic disease through its effect on
metabolites
15
HMGCR/
statins
Metabolites Causal Shows consistencyof observational data on statins
versus predicted MR effects on metabolites
16
Adiposity
(BMI and
waist–hip
ratio)
CHD BMI and waist–hipratio
(adjusted for BMI) causally
increases risk of CHD
No trial has yet shown this causal relationship 17-
20
CRP CHD No causal relationship No trial of a therapy specific to CRP for CVD events has
been
Conducted
21-23

FRAMINGHAM HEART STUDY
A HISTORY OF MEDICAL SCIENCE FROM CV RISK FACTORS TO GENETIC
Three Generations of Research on Heart Disease
The legacy of 72 years

Framingham Heart Study – A 72 years of legacy
(1948-Till date)
 The longest running, multigenerational longitudinal study in medical history
 In 1948, National Heart Institute (now known as the National Heart, Lung, and Blood Institute or
NHLBI) initiated an ambitious project in health research.
 At the time, little was known about the general causes of heart disease and stroke, but the death
rates for CVD had been increasing steadily since the beginning of the century and had become an
American epidemic.
 The Framingham Heart Study became a joint project of the National Heart, Lung, and Blood
Institute and Boston University.
 The objective was to identify the common factors or characteristics that contribute to CVD by
following its development over a long period of time in a large group of participants who had not
yet developed overt symptoms of CVD or suffered a heart attack or stroke.

Framingham Heart Study: Research Milestones
Sr.No. Year Milestone
1 1948 Framingham Heart Study begins
2 1956 Findings on progression rheumatic heart disease reported
3 1957 High blood pressure and high cholesterol levels shown to increase likelihood of heart disease
4 1959 Some heart attacks discovered to be “silent” (causing no pain)
5 1960 Cigarette smoking found to increase the risk of heart disease
6 1961 The term “risk factor” introduced
7 1961 Cholesterol level, blood pressure, and electrocardiogram abnormalities found to increase the risk of
heart disease
8 1967 Physical activity found to reduce the risk of heart disease and obesity to increase the risk of heart
disease
9 1970 High blood pressure found to increase the risk of stroke
10 1970 Atrial fibrillation increases stroke risk 5-fold

11 1976 Menopause found to increase the risk of heart disease
12 1978 Psychosocial factors found to affect heart disease
13 1988 High levels of HDL cholesterol found to reduce risk of death
14 1994 Enlarged left ventricle (one of two lower chambers of the heart) shown to increase the risk of
stroke
15 1996 Progression from hypertension to heart failure described
16 1998 Framingham Heart Study researchers identify that atrial fibrillation is associated with an
increased risk of all-cause mortality
17 1998 Development of simple coronary disease prediction algorithm involving risk factor categories to
allow physicians to predict multivariate coronary heart disease risk in patients without overt
CHD
18 1999 Lifetime risk at age 40 years of developing coronary heart disease is one in two for men and one
in three for women

19 2001 High-normal blood pressure is associated with an increased risk of cardiovascular disease,
emphasizing the need to determine whether lowering high-normal blood pressure can reduce
the risk of cardiovascular disease
20 2002 Lifetime risk of developing high blood pressure in middle-aged adults is 9 in 10
21 2002 Obesity is a risk factor for heart failure
22 2004 Serum aldosterone levels predict future risk of hypertension in non-hypertensive individuals
23 2005 Lifetime risk of becoming overweight exceeds 70 percent, that for obesity approximates 1 in 2
24 2006 The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health
announces a new genome-wide association study at the Framingham Heart Study in
collaboration with Boston University School of Medicine to be known as the SHARe project (SNP
Health Association Resource)

25 2007 Based on evaluation of a densely interconnected social network of 12,067 people
assessed as part of the Framingham Heart Study, network phenomena appear to be
relevant to the biologic and behavioral trait of obesity, and obesity appears to spread
through social ties
26 2008 Based on analysis of a social network of 12,067 people participating in the Framingham
Heart Study (FHS), researchers discover that social networks exert key influences on
decision to quit smoking
27 2008 Discovery by Framingham Heart Study and publication of four risk factors that raise
probability of developing precursor of heart failure; new 30-year risk estimates developed
for serious cardiac events
28 2009 Framingham Heart Study cited by the American Heart Association among the top 10
cardiovascular research achievements of 2009, “Genome-wide Association Study of Blood
Pressure and Hypertension: Genome-wide association study identifies eight loci associated with
blood pressure”

29 2009 A new genetic variant associated with increased susceptibility for atrial fibrillation, a
prominent risk factor for stroke and heart failure, is reported in two studies based on data
from the Framingham Heart Study
30 2009 Framingham Heart Study researchers find parental dementia may lead to poor memory
in middle-aged adults
31 2009 Framingham Heart Study researchers find high leptin levels may protect against
Alzheimer’s disease and dementia
32 2009-
10
Framingham Heart Study researchers contribute to discovering hundreds of new genes
underlying major heart disease risk factors—body mass index, blood cholesterol,
cigarette smoking, blood pressure and glucose/diabetes
33 2010 Sleep apnea tied to increased risk of stroke
34 2010 Framingham Heart Study researchers identify additional genes that may play a role in
Alzheimer’s disease

35 2010 Framingham Heart Study finds fat around the abdomen associated with smaller, older
brains in middle-aged adults
36 2010 Framingham Heart Study finds genes link puberty timing and body fat in women
37 2010 Having first-degree relative with atrial fibrillation associated with increased risk for this
disorder
38 2010 First definitive evidence that occurrence of stroke by age 65 years in a parent increased
risk of stroke in offspring by 3-fold
39 2011 Several exciting genome projects are underway. Large parts of the sequence of DNA for
hundreds of Framingham participants are being analyzed in 2011 in two large studies,
the NHLBI Large-Scale DNA Sequencing Project and the U.S. Cohorts for Heart and
Aging Research in Genomic Epidemiology

40 2012 Framingham researchers find associations between new metabolites (including amino
acids glutamate and glutamine) and adverse metabolic profiles that predispose to risk of
developing diabetes, heart disease, or stroke
41 2012 Framingham researchers find that higher vascular stiffness is a precursor, instead of the
result of hypertension in middle-aged adults
42 2012 Framingham researchers identify new biomarkers reflecting myocardial and vascular
stress that predict future risk of developing cardiovascular events in low to intermediate
risk individuals
43 2013 New genetic loci associated with blood lipid levels (Low-density lipoprotein cholesterol,
triglycerides, and high-density lipoprotein cholesterol) are reported in a study based on
data from Framingham Heart Study
44 2013 Genetic variant of MUC5B may identify people at a high risk of developing interstitial
lung abnormalities and pulmonary fibrosis in a study based on Framingham Heart Study
data

45 2013 New associations found between certain peripheral blood gene expression patterns and
risk of developing coronary heart disease, based on Framingham Heart Study data
46 2013 Genetic variation in the gene LPA is associated with aortic-valve calcification, a risk
factor for developing aortic-valve disease, based in part on Framingham Heart Study
data
47 2014 Report highlights the association between age of adult menarche and adult BMI and
select genetic variants
48 2015 Discovery of genetic variants that may influence brain structure, which may help
elucidate the genetic mechanisms contributing to neurodegenerative disease
49 2016 Over three decades, the incidence rate of dementia has declined in Framingham Heart
Study participants, especially in those with a high school diploma
50 2017 A game-based intervention that increased social incentives led to increased physical
activity among Framingham Heart study participants

51 2017 A game-based intervention that increased social incentives led to increased physical
activity among Framingham Heart study participants
52 2017 Presence of three major anatomic components of risk on CT imaging, i.e., coronary
calcification, excess adiposity, and greater muscle fat, across multiple organs are
associated with greater levels of cardiovascular disease risk factors and overall mortality
in Framingham Heart Study participants
53 2018 Framingham Heart Study researchers find that former smokers who quit smoking 25 or
more years ago still have three times as much risk of developing lung cancer compared
to people who have never smoked

70-year legacy of the Framingham Heart Study
 The Framingham Heart Study (FHS) was established in 1948 to improve understanding of the epidemiology of coronary heart disease
(CHD) in the USA.
 In 1961, seminal work identified major risk factors for CHD (high blood pressure, high cholesterol levels and evidence on the
electrocardiogram of left ventricular hypertrophy), which later formed the basis for multivariable 10-year and 30-year risk-prediction
algorithms.
 The FHS cohorts now comprise three generations of participants (n ≈ 15,000) and two minority cohorts. The FHS cohorts are densely
phenotyped, with recurring follow-up examinations and surveillance for cardiovascular and non-cardiovascular end points.
 Assessment of subclinical disease and physiological profiling of these cohorts (with the use of echocardiography, ambulatory
electrocardiographic monitoring, exercise stress testing, cardiac CT, heart and brain MRI, serial vascular tonometry and accelerometry)
have been performed repeatedly. Over the past decade, the FHS cohorts have undergone deep ‘omics’ profiling (including whole-
genome sequencing, DNA methylation analysis, transcriptomics, high-throughput proteomics and metabolomics, and microbiome
studies).
 The FHS is a rich, longitudinal, transgenerational and deeply phenotype cohort study with a sustained focus on state-of-the-art
epidemiological methods and technological advances to facilitate scientific discoveries.
 https://www.nature.com/articles/s41569-019-0202-5

25 March 2018RAJENDRA JANI, JANIRH@GMAIL.COM 52

Cardiology research 25 july 2020

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