Devaki Nair | Royal free Hospital (original) (raw)

Papers by Devaki Nair

BMJ open, Jan 5, 2018

To assess changes in metabolic risk factors and cancer-related growth factors associated with sho... more To assess changes in metabolic risk factors and cancer-related growth factors associated with short-term abstinence from alcohol. Prospective, observational study. Single tertiary centre. Healthy subjects were recruited based on intention to: (1) abstain from alcohol for 1 month (abstinence group), or (2) continue to drink alcohol (control group). Inclusion criteria were baseline alcohol consumption >64 g/week (men) or >48 g/week (women). Exclusion criteria were known liver disease or alcohol dependence. The primary outcome was change in insulin resistance (homeostatic model assessment (HOMA) score). Secondary outcomes were changes in weight, blood pressure (BP), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and liver function tests. Primary and secondary outcomes were adjusted for changes in diet, exercise and cigarette smoking. The abstinence group comprised 94 participants (mean age 45.5 years, SD ±1.2) and the control group 47 participants (mean ...

Archives of Medical Science, 2015

The ear lobe crease (ELC) has been defined as a deep wrinkle that extends backwards from the trag... more The ear lobe crease (ELC) has been defined as a deep wrinkle that extends backwards from the tragus to the auricle. It has been proposed that ELC is a predictor of coronary artery disease (CAD). In this review, we consider the possible association between ELC and CAD. Our aim is to systematically address all the relevant evidence in this field. There are many studies that support an association between ELC and CAD. However, other studies did not find such an association. A recent meta-analysis supports the hypothesis that ELC could be a marker of CAD. However, several limitations raise doubts as to whether we should accept this link.

Annals of clinical biochemistry, Jan 15, 2016

A "one stop shop" model for multifactorial risk factor management in a culturally sensi... more A "one stop shop" model for multifactorial risk factor management in a culturally sensitive environment may improve cardiovascular disease (CVD) and diabetes prevention. A full biochemical profile for CVD risk assessment includes a lipid profile, glucose, glycated haemoglobin (HbA1 c) and urine albumin creatinine ratio (UACR) measurements. This may require the use of more than one point of care testing (POCT) instrument. Individuals who attended a community CVD risk screening or an audit programme of the diabetic care pathway in the community were sampled. Bland-Altman and Deming regression plots were used to assess agreement between methods for total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), HbA1 c, and UACR. There was good agreement between the Afinion AS100 analyser, Cholestech LDX and the laboratory methods for TC, HDL-C and TG (n=232). The Afinion AS100 agreed well with the laboratory method for HbA1 c (n=255) and UACR (n=176)...

Seizure, 2014

Epilepsy is associated with increased cardiovascular disease (CVD) morbidity and mortality. The e... more Epilepsy is associated with increased cardiovascular disease (CVD) morbidity and mortality. The exact causes of this link are not clearly defined. The role of antiepileptic drugs (AEDs) in influencing CVD risk in patients with epilepsy remains controversial. A link between epilepsy, AEDs and cardiac arrhythmias has been proposed and may be responsible for sudden unexpected death in epilepsy (SUDEP). Methods: We searched MEDLINE up to December 1, 2013 for relevant publications using combinations of keywords. We also examined the reference list of articles identified by this search and selected those we judged relevant. These were included in this narrative review. Results: AEDs may exert both beneficial and adverse cardiovascular effects. This narrative review considers the influence of AEDs on some predictors of vascular risk [i.e. weight, insulin resistance, metabolic syndrome, lipids, lipoprotein (a), C-reactive protein, homocysteine, vitamins, coagulation factors, uric acid, carotid intima media thickness, markers of oxidative status and matrix metalloproteinase-9]. Certain AEDs can also have pro-arrhythmic properties. Conclusions: AEDs may exert different effects on various established and emerging predictors of vascular risk. Furthermore, pharmacokinetic interactions between AEDs and drugs used to reduce vascular risk (e.g. statins) need to be better documented. Whether this knowledge, in terms of individualizing antiepileptic and CVD prevention treatment, will prove to be relevant in clinical practice remains to be established.

Kidney International, 1991

Effects of dietary fatty acids in an animal model of focal glomerulosclerosis. The obese Zucker r... more Effects of dietary fatty acids in an animal model of focal glomerulosclerosis. The obese Zucker rat develops hyperlipidemia, proteinuria and focal glomeruloscierosis without prior changes in renal hemodynamics. To study the effects of oral fatty acid intake on the development of renal injury in this model, rats were fed standard chow or chow supplemented with either 14% fish oil or 14% beef tallow after unilateral nephrectomy at the age of 10 weeks. At 32 weeks post-nephrectomy animals were sacrificed and renal tissue saved to assess histology and glomerular eicosanoid production. Fish-oil treated rats had lower mean plasma cholesterol levels and developed less proteinuria than control or tallow-fed animals although there was no difference in plasma creatinine or blood pressure. Histological analysis showed significantly fewer scierosed glomeruli in the fish oil group (4.0 0.8% vs. control 19.4 4.1%, P < 0.0005 and vs. beef tallow 10.8 1.9%, P < 0.005). Glomeruli derived from rats on fish oil supplements produced smaller amounts of prostaglandin (PG)E2 and of the stable metabolites of PGI2 (6-oxo-PGF1,j, PGF2 (PGF2,) and thromboxane (TX)A2 (TXB2) than those from tallow-fed animals. This study demonstrates that oral fatty acid intake may influence the development of glomerulosclerosis. The apparent beneficial effects of fish oil have not been fully defined, but may relate to favorable changes in plasma lipid concentration and renal eicosanoid production. After a critical reduction in renal mass, organ failure may progress even after the original insult has ceased [1]. The glomeruli of this end stage kidney show the histological changes of glomerulosclerosis, a lesion also seen in a variety of animal models of renal disease [211. The mechanisms underlying the development of glomeruloscierosis are not fully understood. Studies in rats subjected to 5/ nephrectomy led Brenner and colleagues to propose that an increase in intraglomerular pressures and flow rates in remnant nephrons contributed to progressive renal injury [31. Although much attention has focused on the possible detrimental effects of hyperfiltration, other factors including intraglomerular coagulation, altered renal eicosanoid production and abnormalities of lipid metabolism may also contribute to glomerular scarring [4-6]. The obese Zucker rat provides a model of spontaneous. glomerulosclerosis. Rats inherit obesity as an autosomal reces

Atherosclerosis, 2014

Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disease ... more Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disease caused by deleterious mutations in the LIPA gene. The age at onset and rate of progression vary greatly and this may relate to the nature of the underlying mutations. Patients presenting in infancy have the most rapidly progressive disease, developing signs and symptoms in the first weeks of life and rarely surviving beyond 6 months of age. Children and adults typically present with some combination of dyslipidaemia, hepatomegaly, elevated transaminases, and microvesicular hepatosteatosis on biopsy. Liver damage with progression to fibrosis, cirrhosis and liver failure occurs in a large proportion of patients. Elevated low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels are common features, and cardiovascular disease may manifest as early as childhood. Given that these clinical manifestations are shared with other cardiovascular, liver and metabolic diseases, it is not surprising that LAL-D is under-recognized in clinical practice. This article provides practical guidance to lipidologists, endocrinologists, cardiologists and hepatologists on how to recognize individuals with this life-limiting disease. A diagnostic algorithm is proposed with a view to achieving definitive diagnosis using a recently developed blood test for lysosomal acid lipase. Finally, current management options are reviewed in light of the ongoing development of enzyme replacement therapy with sebelipase alfa (Synageva BioPharma Corp., Lexington, MA, USA), a recombinant human lysosomal acid lipase enzyme.

Current Pharmaceutical Design, 2015

Statins exert beneficial effects on cardiovascular [CV] outcomes as well as on inflammation and o... more Statins exert beneficial effects on cardiovascular [CV] outcomes as well as on inflammation and oxidative stress. The widespread use of statins for both primary and secondary CV disease prevention is based on the evidence from large randomized controlled trials. The benefits of statin treatment outweigh any harm in high risk patients. In this narrative review, we provide an update on several aspects of statin treatment based on the most recent evidence in this field.

Journal of Clinical Lipidology, 2020

BACKGROUND: Rates of atherosclerotic cardiovascular disease (ASCVD) are strikingly high in India ... more BACKGROUND: Rates of atherosclerotic cardiovascular disease (ASCVD) are strikingly high in India compared to Western countries and are increasing. Moreover, ASCVD events occur at a younger age with only modest hypercholesterolemia, most commonly with low levels of high-density lipoprotein cholesterol. The course of ASCVD also appears to be more fulminant with higher mortality. OBJECTIVE: In light of these issues, the Lipid Association of India (LAI) endeavored to develop revised guidelines with more aggressive low-density lipoprotein cholesterol (LDL-C) goals in secondary prevention and for patients with familial hypercholesterolemia compared to guidelines in the United States and other countries. METHODS: Owing to the paucity of clinical outcomes data in India, it was necessary to place major emphasis on expert opinion as a complement to randomized placebo-controlled data generated mostly in non-Indian cohorts. To facilitate this process, the LAI conducted a series of 19 meetings among 162 lipid specialists in 13 cities throughout India over a period of 11 months before formulating this expert consensus statement. RESULTS: The LAI recommends an LDL-C goal ,50 mg/dL in all patients in secondary prevention or very high-risk primary prevention but proposes an optional goal #30 mg/dL in category A extreme-risk patients (eg, coronary artery disease 1 familial hypercholesterolemia) and a recommended goal #30 mg/dL in category B extreme-risk patients [coronary artery disease 1 (1) diabetes and polyvascular disease/$3 major ASCVD risk factors/end organ damage, or (2) recurrent acute coronary syndrome within 12 months despite LDL-C ,50 mg/dL, or (3) homozygous familial hypercholesterolemia]. CONCLUSIONS: More aggressive LDL-C goals are needed for prevention of ASCVD in India, as described in this expert consensus statement. Use of statins and ezetimibe needs to increase in India in combination with improved control of other ASCVD risk factors. Proprotein convertase subtilisin kexin type 9 inhibitors can improve LDL-C goal achievement in patients with refractory hypercholesterolemia.

Current Vascular Pharmacology, 2021

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in ... more Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in very high risk group and extreme risk group (category A) of <50 mg/dl (1.3 mmol/l) while the LDL-C goal for extreme risk group (category B) is ≤30 mg/dl (0.8 mmol/l). High intensity statins are the first-line lipid lowering therapy. Nonstatin therapy like ezetimibe and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors may be added as an adjunct to statins in patients who do not achieve LDL-C goals with statins alone. In acute ischaemic stroke, high intensity statin therapy improves neurological and functional outcomes regardless of thrombolytic therapy. Although conflicting data exist regarding increased risk of intracerebral haemorrhage (ICH) with statin use, the overall benefit risk ratio favors long-term statin therapy necessitating detailed discussion with the patient. Patients who have statins withdrawn while being on prior statin therapy at the time of acute ischaemic stroke have worse functional outcomes and increased mortality. LAI recommends that statins be continued in such patients. In patients presenting with ICH, statins should not be started in the acute phase but should be continued in patients who are already taking statins. ICH patients, once stable, need risk stratification for atherosclerotic cardiovascular disease (ASCVD).

Sultan Qaboos University medical journal, 2013

Ashfaq et al. 1 reported a significant correlation between circulating lipoprotein(a) [Lp(a)] lev... more Ashfaq et al. 1 reported a significant correlation between circulating lipoprotein(a) [Lp(a)] levels and the severity of coronary atherosclerosis (as assessed by the SYNTAX score) in a North Indian population. The authors suggested that Lp(a) levels of >20 mg/dl predict the severity of coronary atherosclerosis. A few additional comments may be of interest to readers. Studies have found a positive correlation between Lp(a) and total cholesterol or low-density lipoprotein cholesterol (LDL-C) levels but an inverse association with triglyceride (TG) levels in patients with diabetes mellitus (DM). 2 Ashfaq et al. 1 did not discuss the relationship between LDL-C and Lp(a). In addition, the authors showed that Lp(a) levels tended to be higher at raised TG levels. 1 It would be useful to know how many patients in this study had DM. Ashfaq et al. 1 did not include the details of the kit used for the Lp(a) measurement and the precision data at the different Lp(a) levels. The problems with isoform specificity in Lp(a) measurements, the sub-optimal performance of the different assays and the lack of commutability across Lp(a) assay systems are well-known. 3 Population studies show that females after the age of 45 years tend to have higher Lp(a) values than men of the same age. 4 Also, hormone replacement therapy can reduce the plasma concentration of Lp(a). 5 The authors did not describe the effect of gender on Lp(a) nor show the numbers of females in the two groups and whether some of these women were on HRT. If there were more women in one group than the other, this may have influenced the distribution of Lp(a) concentrations. Lp(a) values are known not to be normally distributed. 6 Therefore, the preferred statistical evaluation is to use nonparametric tests and the data should be expressed in medians and ranges. In addition, the cutoff value (>20 mg/dl) proposed by Ashfaq et al. 1 could be influenced by the use of the mean ± standard deviation. By using a receiver operating characteristic curve analysis and calculating the area under the curve, the accuracy of a diagnostic test can be determined and used to predict the best cutoff value by showing the sensitivity and specificity of the test at a certain cutoff point. In our opinion, it would be interesting to carry out such a procedure for this particular study and to see the results.

Oman Medical Journal, 2013

Abstract Lifestyle management is the cornerstone of both primary and secondary prevention of athe... more Abstract Lifestyle management is the cornerstone of both primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) and the importance of lifestyle management is emphasised by all major guidelines. Despite this, actual implementation of lifestyle management is poor. Lifestyle modification includes smoking cessation, weight loss, dietary change, increasing physical inactivity, and stress management. This review summarises evidence-based opportunities and challenges for healthcare professionals to promote healthy lifestyles at an individual level for the prevention of ASCVD.