Krishnarajah Nirantharakumar

Krishnarajah Nirantharakumar

orcid

Research Focus & Metrics

Academic Career Length

15Years (2012-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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25 July 2022 in Nature Medicine
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ASAnuradhaa Subramanian
Anuradhaa Subramanian
KNKrishnarajah Nirantharakumar
Krishnarajah Nirantharakumar
SHSarah E Hughes
Sarah E Hughes
PMPuja Myles
Puja Myles
TWTim Williams
Tim Williams
SHShamil Haroon
Shamil Haroon
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02–8.39), hair loss (3.99, 3.63–4.39), sneezing (2.77, 1.40–5.50), ejaculation difficulty (2.63, 1.61–4.28) and reduced libido (2.36, 1.61–3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.

7 October 2020 in BMJ
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KOKelvin Okoth
Kelvin Okoth
JCJoht Singh Chandan
Joht Singh Chandan
TMTom Marshall
Tom Marshall
STShakila Thangaratinam
Shakila Thangaratinam
GTG Neil Thomas
G Neil Thomas
NANicola J Adderley
Nicola J Adderley
Objective To consolidate evidence from systematic reviews and meta-analyses investigating the association between reproductive factors in women of reproductive age and their subsequent risk of cardiovascular disease. Design Umbrella review. Data sources Medline, Embase, and Cochrane databases for systematic reviews and meta-analyses from inception until 31 August 2019. Review methods Two independent reviewers undertook screening, data extraction, and quality appraisal. The population was women of reproductive age. Exposures were fertility related factors and adverse pregnancy outcomes. Outcome was cardiovascular diseases in women, including ischaemic heart disease, heart failure, peripheral arterial disease, and stroke. Results 32 reviews were included, evaluating multiple risk factors over an average follow-up period of 7-10 years. All except three reviews were of moderate quality. A narrative evidence synthesis with forest plots and tabular presentations was performed. Associations for composite cardiovascular disease were: twofold for pre-eclampsia, stillbirth, and preterm birth; 1.5-1.9-fold for gestational hypertension, placental abruption, gestational diabetes, and premature ovarian insufficiency; and less than 1.5-fold for early menarche, polycystic ovary syndrome, ever parity, and early menopause. A longer length of breastfeeding was associated with a reduced risk of cardiovascular disease. The associations for ischaemic heart disease were twofold or greater for pre-eclampsia, recurrent pre-eclampsia, gestational diabetes, and preterm birth; 1.5-1.9-fold for current use of combined oral contraceptives (oestrogen and progesterone), recurrent miscarriage, premature ovarian insufficiency, and early menopause; and less than 1.5-fold for miscarriage, polycystic ovary syndrome, and menopausal symptoms. For stroke outcomes, the associations were twofold or more for current use of any oral contraceptive (combined oral contraceptives or progesterone only pill), pre-eclampsia, and recurrent pre-eclampsia; 1.5-1.9-fold for current use of combined oral contraceptives, gestational diabetes, and preterm birth; and less than 1.5-fold for polycystic ovary syndrome. The association for heart failure was fourfold for pre-eclampsia. No association was found between cardiovascular disease outcomes and current use of progesterone only contraceptives, use of non-oral hormonal contraceptive agents, or fertility treatment. Conclusions From menarche to menopause, reproductive factors were associated with cardiovascular disease in women. In this review, presenting absolute numbers on the scale of the problem was not feasible; however, if these associations are causal, they could account for a large proportion of unexplained risk of cardiovascular disease in women, and the risk might be modifiable. Identifying reproductive risk factors at an early stage in the life of women might facilitate the initiation of strategies to modify potential risks. Policy makers should consider incorporating reproductive risk factors as part of the assessment of cardiovascular risk in clinical guidelines. Systematic review registration PROSPERO CRD42019120076.

16 January 2018 in PLOS Medicine
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BDBarbara Daly
Barbara Daly
KTKonstantinos A Toulis
Konstantinos A Toulis
GTG.Neil Thomas
G.Neil Thomas
KGKrishna Margadhamane Gokhale
Krishna Margadhamane Gokhale
JMJames Martin
James Martin
KNKrishnarajah Nirantharakumar
Krishnarajah Nirantharakumar
Gestational diabetes mellitus (GDM) is associated with developing type 2 diabetes, but very few studies have examined its effect on developing cardiovascular disease. We conducted a retrospective cohort study utilizing a large primary care database in the United Kingdom. From 1 February 1990 to 15 May 2016, 9,118 women diagnosed with GDM were identified and randomly matched with 37,281 control women by age and timing of pregnancy (up to 3 months). Adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated for cardiovascular risk factors and cardiovascular disease. Women with GDM were more likely to develop type 2 diabetes (IRR = 21.96; 95% CI 18.31–26.34) and hypertension (IRR = 1.85; 95% CI 1.59–2.16) after adjusting for age, Townsend (deprivation) quintile, body mass index, and smoking. For ischemic heart disease (IHD), the IRR was 2.78 (95% CI 1.37–5.66), and for cerebrovascular disease 0.95 (95% CI 0.51–1.77; p-value = 0.87), after adjusting for the above covariates and lipid-lowering medication and hypertension at baseline. Follow-up screening for type 2 diabetes and cardiovascular risk factors was poor. Limitations include potential selective documentation of severe GDM for women in primary care, higher surveillance for outcomes in women diagnosed with GDM than control women, and a short median follow-up postpartum period, with a small number of outcomes for IHD and cerebrovascular disease. Women diagnosed with GDM were at very high risk of developing type 2 diabetes and had a significantly increased incidence of hypertension and IHD. Identifying this group of women in general practice and targeting cardiovascular risk factors could improve long-term outcomes.

7 June 2019 in The British Journal of Psychiatry
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JCJoht Singh Chandan
Joht Singh Chandan
TTTom Thomas
Tom Thomas
CBCaroline Bradbury-Jones
Caroline Bradbury-Jones
RRRebecca Russell
Rebecca Russell
SBSiddhartha Bandyopadhyay
Siddhartha Bandyopadhyay
JTJulie Taylor
Julie Taylor
Background: Internationally, intimate partner violence (IPV) cohorts have demonstrated associations with depression and anxiety. However, this association has not yet been described in a UK population, nor has the association with serious mental illness (SMI).Aims: To explore the relationship between IPV exposure and mental illness in a UK population.Method: We designed a retrospective cohort study whereby we matched 18 547 women exposed to IPV to 74 188 unexposed women. Outcomes of interest (anxiety, depression and SMI) were identified through clinical codes.Results: At baseline, 9174 (49.5%) women in the exposed group had some form of mental illness compared with 17 768 (24.0%) in the unexposed group, described as an adjusted odds ratio of 2.62 (95% CI 2.52–2.72). Excluding those with mental illness at baseline, 1254 exposed women (incidence rate 46.62 per 1000 person-years) went on to present with any type of mental illness compared with 3119 unexposed women (incidence rate 14.93 per 1000 person-years), with an aIRR of 2.77 (95% CI 2.58–2.97). Anxiety (aIRR 1.99, 95% CI 1.80–2.20), depression (aIRR 3.05, 95% CI 2.81–3.31) and SMI (aIRR 3.08, 95% CI 2.19–4.32) were all associated with exposure to IPV.Conclusions: IPV remains a significant public health issue in the UK. We have demonstrated the significant recorded mental health burden associated with IPV in primary care, at both baseline and following exposure. Clinicians must be aware of this association to reduce mental illness diagnostic delay and improve management of psychological outcomes in this group of patients.

28 March 2018 in PLOS Medicine
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BKBalachandran Kumarendran
Balachandran Kumarendran
MOMichael W O'Reilly
Michael W O'Reilly
KMKonstantinos N Manolopoulos
Konstantinos N Manolopoulos
KTKonstantinos A Toulis
Konstantinos A Toulis
KGKrishna Margadhamane Gokhale
Krishna Margadhamane Gokhale
KNKrishnarajah Nirantharakumar
Krishnarajah Nirantharakumar
Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86–2.66, p < 0.001), also after adjusting for BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16–4.53, p = 0.017 for 3–3.49 nmol/L and HR = 2.40, 95% CI 1.24–4.66, p = 0.009 for >3.5 nmol/L). Mirroring this finding, SHBG <30 nmol/L was associated with increased NAFLD hazard (HR = 4.75, 95% CI 2.44–9.25, p < 0.001 for 20–29.99 nmol/L and HR = 4.98, 95% CI 2.45–10.11, p < 0.001 for <20 nmol/L). Limitations of this study include its retrospective nature, absence of detailed information on criteria used to diagnosis PCOS and NAFLD, and absence of data on laboratory assays used to measure serum androgens. We found that women with PCOS have an increased rate of NAFLD. In addition to increased BMI and dysglycemia, androgen excess contributes to the development of NAFLD in women with PCOS. In women with PCOS-related androgen excess, systematic NAFLD screening should be considered.

1 March 2022 in Annals of Internal Medicine
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APAlessandro Prete
Alessandro Prete
ASAnuradhaa Subramanian
Anuradhaa Subramanian
IBIrina Bancos
Irina Bancos
VCVasileios Chortis
Vasileios Chortis
STStylianos Tsagarakis
Stylianos Tsagarakis
EIENSAT EURINE-ACT Investigators*
ENSAT EURINE-ACT Investigators*
Benign adrenal tumors are commonly discovered on cross-sectional imaging that is done for other reasons. This study examined whether the mild autonomous cortisol secretion often found with these tu... Visual Cardiometabolic Disease Burden in Benign Adrenal Tumors. Benign adrenal tumors are commonly discovered on cross-sectional imaging that is done for other reasons. This study examined... Background: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in ...