The FDA approved alirocumab (Praluent), the first monoclonal antibody to inhibit a protein called PCSK9 that was discovered a decade back. Cholesterol is cleared by receptors in the liver and these receptors are degraded by PCSK9. So if you block PCSK9, the cholesterol clearing receptors remain intact and active, pulling down cholesterol levels from the body.
Mr. Mohammad Ali Jinnah during his remarkable life had little idea that studies of the human gene would go on to confirm that mankind originated from the continent of Africa. The great dispersal began 100,000 years ago because of severe droughts that emptied the Great Lakes of Africa; these mega droughts reduced the water content of lake Malawi by more than 85%. There is archeological and genetic evidence that large groups of modern humans trekked out of Africa to colonize the Middle East, South Asia, South East Asia and Australia, whilst another group of modern humans headed north to Europe. The simple conclusion from the extensive data is that we humans regardless of the color of our skin, religious beliefs, caste or social status are quite similar because we belong to just one species-homo sapiens.
Recently an 85-year old man who had had CABG 2 decades ago was transferred from another hospital for self-terminating sustained monomorphic ventricular tachycardia (VT). On arrival he had a heart rate of 80 per minute, blood pressure of 106/68 mm Hg, oxygen saturation of 95% on room air, his ECG showed sinus rhythm with old anterior myocardial infarction, and 2 D echocardiogram revealed severe septal/apical wall motion abnormality with an ejection fraction of 25%. The patient conceded that he had suffered a heart attack more than 25 years ago and was currently not on any specific treatment despite having symptoms of shortness of breath and tiredness.
The last 5 years have have delivered a couple of very exciting new anti-platelet (AP) drugs that bring along with them considerable advantages of efficacy along with some safety issues. We had aspirin for decades and were doing quite well but the introduction of stent thrombosis mandated research on more powerful AP’s. It is however crucial we understand their mechanisms of action and adverse effects. Aspirin has been used for hundreds of years for a variety of ailments A Nobel Prize has been won on research on counter effects of aspirin on prostaglandins. Aspirin is mandatory for secondary prevention of cardiovascular disease at a remarkably low dose of 75-80 mg a day. Aspirin blocks the thromboxane receptors and thus prevents formation of blood clots.
One of the commonest life- saving procedures is percutaneous coronary intervention (PCI) invoving percutaneous coronary angioplasty (PTCA) accompanied by insertion of a stent in patients presenting with acute coronary syndrome. The procedure of PCI has been guided all these decades by coronary angiography in which a dye (or contrast) is injected through a catheter (a thin tube) into the coronary artery under X-Ray vision. More than a million such procedures are performed annually in the USA and a similar amount across Europe. Percutaneous coronary intervention has rapidly replaced open-heart surgery in a significant number of patients ; it has further gained popularity with introduction of more powerful anti-platelet agents and development of second generation drug-eluting stents.
Continue reading “IVUS OR FFR GUIDED PCI VERSUS ANGIOGRAPHY ALONE.”
It is well known that the sooner an infarct related coronary artery is opened to restore antegrade flow the greater would be reduction in infarct size which in turn apart from reducing morbidity will actually improve survival. Restoration of myocardial perfusion subsequent to a ST-segment elevation (STEMI) myocardial infarction is best achieved by primary percutaneous intervention (PPCI) involving negotiating a guide wire through the coronary artery block, followed by balloon angioplasty and deployment of a coronary stent. However it has also been observed during experimental and clinical conditions that reperfusion of blood flow into infarcted territory can paradoxically increase cell death and myocardial damage. Mitochondria play a key role in the phenomenon of reperfusion injury (RI) by releasing toxic chemicals from the inner membrane via irreversible opening a channel named ‘mitochondrial permeability transition pore’ (MPTP). Researchers have therefore been trying to identify a suitable intervention to prevent opening of mitochondrial MPTP. Moreover experimental evidence suggests that preventing opening of MPTP may reduce infarct size (IS) by an additional 30% to 50% in various animal models.
Undoubtedly 2016 has been a remarkable year so far. More than 20% of global stocks (worth $15 trillion). One of the worst blizzards lashed Washington DC on 22nd January, leaving hundreds of thousands of people without power and damage is estimated in the billions of dollars. New York City’s Central Park got buried under 27 inches of snow. A strong El Nino has been repeatedly slamming the west coast of the US with brutal storms. Camus may have called it a charming beginning.
Continue reading “WITH DENGUE IN , CAN ZIKA BE FAR BEHIND ?”
Calcific degenerative aortic stenosis (AS) is a common acquire valvular disease largely affecting older people. There is restriction of leaflet mobility due to valve calcification leading to outflow obstruction. We have known for almost half a century that the natural history of valvular aortic stenosis includes a long asymptomatic during which there are few morbid events, followed by symptoms of angina, syncope and shortness of breath that predict a high mortality rate. It was confirmed over the next 4 decades that 50% of symptomatic patients managed without surgery dies over 2-3 years. But asymptomatic AS carried a low mortality rate even if severe (peak aortic velocity of >4 m/s, mean gradient across aortic valve of >40 mm Hg, or aortic valve area < 1.0 cm2). There were no deaths in a cohort of 123 asymptomatic patients with AS followed for 2.5 years (Otto et al). Only one patient suffered sudden death in a series of 116 asymptomatic patients with very severe AS (V max > 5m/s). Hence AS is a slowly progressive disease with survival during the asymptomatic phase quite similar to that of age matched controls with low risk of sudden death. The potential benefit of aortic valve replacement (AVR) in asymptomatic severe AS has not been observed to outweigh the risk of operative death. Hence guidelines recommend waiting during the asymptomatic phase and AVR once symptoms set in.
Continue reading “SURGERY FOR ASYMPTOMATIC SEVERE AORTIC STENOSIS.”
Peripartum cardiomyopathy (PCM) is an uncommon disease in which pregnant women present with systolic heart failure (during last month of pregnancy and with 5 months post of delivery of the baby). The incidence of PCM varies from 1 in 100 in Haiti, 1 in 300 in Nigeria and 1 in 4000 in Europe. Advanced age, preeclampsia and twins are well known risk factors for PCM. The disease may not resolve in a sizeable number of patients and carries a death rate of at least 10%. One fourth of deaths are attributed to sudden cardiac death because of ventricular tachyarrhythmias.
Continue reading “COMMON GENETIC PREDISPOSITION IN PERIPARTUM AND DILATED CARDIOMYOPATHY.”
The world as most of us know has never hurtled down to chaos at such incredible speed. There are devastating floods within weeks of one another in Chennai, Northern England, Latin America and the USA. The earth rumbles under us from Afghanistan to Manipur within days of each other. Delhi along with Beijing is a gas chamber. An air base in Pathankot gets attacked with impunity by Pakistani terrorists and before the area is sanitized the politicians are congratulating one another for the fighting response; apparently 2 terrorists are still hidden somewhere in the area. The question is whom does one believe now. How is one so certain that there are 2 more infiltrators around because there could be more? Worse is the realization that 7 of our brave hearts are dead and as per reports 22 wounded. Five extremists have been shot dead in the encounter. The attack regretfully came days after Modi ji hugged the elected prime minister of Pakistan on the latter’s birthday in Lahore. Terrific response by our good neighbors.
Continue reading “FROM THE ASSASSINATION OF GENERAL PATTON TO THE ROYAL FOLKS FROM PHILIPS.”
There is now a tsunami of evidence that air pollution by increased particulate matter raises the incidence of cardiovascular disease, hypertension, diabetes, respiratory diseases,and lung cancer. Bad air impedes optimal growth of lungs in children and also adversely affects cognition. There are reports that bad air can lead to Alzheimer’s and Parkinsonism too. Delhi has gathered for itself the dubious distinction of being the most polluted city in the world. Delhi has in stridden ahead of Beijing where dirty air is concerned. The state and central governments are making the necessary noises but predictably have not as yet come up with a concrete action plan. The state government displaying helplessness has come up with an anaemic plan of permitting odd and even number registered cars to move on alternate days. But then the current government cannot be blamed for the crisis. The Supreme Court mercifully is definitely seized of the grave problem and is deliberating on imposition of necessary remedial measures. It has in the mean time banned sale of diesel SUV’s till April next year.
The New England Journal of Medicine took the unprecedented step of not only publishing the SPRINT trial on hypertension but also adding 2 editorials, a perspective and a clinical decision article on treatment of hypertension in the same issue, along side the original article.The message is resounding; we now have a large randomised study documenting lowering of systolic blood pressure in a hypertensive population reduces clinical outcomes.
Continue reading “THIS WAS NOT THE ‘SPRINT’ THAT WE HAD COME TO WATCH.”
The sport of athletics truly lies in tatters. An extraordinary World Anti Doping Agency’s (WADA) report has confirmed systemic institutionalised doping involving Russian athletes, coaches trainers, doctors, bureaucrats and even the secret police. The commission goes on to strongly recommend that Russia be blocked from participating in the 2016 Rio Olympics till the countries anti-doping controls are rectified, and that 5 athletes and 5 coaches should be banned for life. The inquiry also recommends that the anti-doping lab in Moscow should lose its accreditation because it indulged in “intentional and malicious destruction” of more than 1400 blood and urine samples despite WADA’s formal notification to preserve them.
Continue reading “ATHLETICS AS A SPORT IS IN TATTERS ; SHOULD INDIAN FEDERATIONS BE CONCERNED ?”
The presence of diabetes substantially alters prognosis and clinical outcomes after percutaneous coronary intervention (PCI). In recent years a number of studies comparing long- term efficacy and safety of various drug eluting stents (DES) have been published and the balance of evidence found to be substantially against the paclitaxel eluting stent (PES).
Continue reading “THIS MAHARAJA IS WEARING NO TUXEDO ! A CASE OF INDUSTRY SPONSORED PROPULSION ?”
Towards the end of 2013 the Eight Joint National Committee (JNC) released the latest guidelines for treatment of adult hypertension. The 14-page document along with 300 pages of online supplement could be summarized into 2 simple messages; keep blood pressure below 150/90 in people over 60 years but below 140/90 in all other adults and that treatment could begin with any one of mainstream anti-hypertensive medication. One could initiate treatment with a thiazide type diuretic, ACE inhibitor, angiotensin receptor blocker (ARB) or a calcium blocker.
There were an estimated 207 million cases of malaria in 2012 according to the official bulletin of the World Health Organization of which 627,000 died but no one is sure and a conservative estimate of the range is between 73000 and 789000 deaths. The problem is that it is impossible to gather accurate mortality data from some countries particularly African ones which suffer the most from the disease. Ninety percent of all malaria deaths occur in sub-Saharan Africa and 77% occur in children below 5 years; 1300 children die each day or one child every minute. Malaria remains a major scourge in the modern world despite recent advances in treatment, prevention and control.
Continue reading “2015 NOBEL PRIZE FOR MEDICINE HONORS DISCOVERY OF ANTI-PARASITIC MEDICINES.”
Probably for the first time a glucose-lowering drug has shown significant 38% relative reduction in cardiovascular mortality and a 32% relative reduction all cause mortality. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor reduces serum glucose levels by cutting down renal reabsorption and increasing urinary excretion of glucose. A large industry sponsored randomized trial examined the effects of empagliflozin on cardiovascular outcomes in 7020 type 2 diabetes patients (mean age 63 years) with previous history of coronary artery disease, stroke, or peripheral arterial disease (EMPA-REG OUTCOME Trial).
Continue reading “THE FIRST ANTI-DIABETIC DRUG TO DEMONSTRATE CARDIOVASCULAR BENEFIT.”
Probably neither the prime minister nor the chief minister of Delhi including their mandarins in the health and urban ministries ever realized that the deadliest stalker on the planet is the mosquito. Mosquitoes kill more than 8 lakhs people in a year with man coming a distant second accounting for 5 lakh kills. The lion slaughters a mere 100 people, while snakes in a year send almost 50,000 to paradise. Astoundingly in all the din most anchors and panelists on television debates have been unable to pronounce Dengue correctly; the emphasis by the media has all along been (with some justification) on slinging as much mud as possible on Delhi hospitals; but not a whisper or murmur of the terrible ramifications of the horrendously dirty city we live in. There has not been the slightest hint suggesting removal of all those puddles of water or administering a vaccine.
A sensational leaked database form the archives of the International Association of Athletics Federations (IAAF) revealing rampant doping among elite medal winning athletes elicited little or no reaction from the Indian media. There was not one editorial, not one column and not a single blog on the biggest ever leak of 12000 blood reports done on 5000 international athletes from 2001 to 2012; of which 800 were considered suspicious by independent experts. A large chunk of these were from athletes in Russia, Ukraine, and Belarus while India contributed about 5% of suspect samples. Surprisingly the database suggested that Kenya too suffered from widespread blood doping including administration of synthetic erythropoietin (EPO) besides anabolic steroids. There have been no pre-competition blood tests of all athletes participating in the current Beijing world championships in which the Kenyans lead with 7 gold medals. Despite serious allegations by the London Times and German TV broadcaster ARD, the IAAF for all practical purposes appears to be disinclined to swoop down on drug cheats.
Continue reading “RAMPANT DOPING IN ATHLETICS NEEDS IMMEDIATE CLEAN UP.”
The new oral anticoagulants (NOAC’s) either directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban and edoxaban). These direct oral anticoagulants have several advantages over vitamin K antagonists; they have a wider therapeutic window, quick onset of action, do not require regular blood coagulation monitoring, and have a shorter half lives. Warfarin (vitamin K antagonist) demands constant monitoring of the international normalized ratio (INR) that in turn compels dose adjustment. The new oral anticoagulants have proven to be viable alternatives to a vitamin K antagonist in industry sponsored randomized trials involving thousands of patients. The NOAC’s when compared to warfarin providing good anticoagulation (INR between 2and 3, 60% of the time) were found to be non-inferior and in some cases superior in patients with non-valvular atrial fibrillation. Intracranial and fatal bleeds were lowered by 50% with the NOAC’s and major bleeding by 28% as compared to warfarin.
Continue reading “IDARUCIZUMAB FOR REVERSAL OF ANTICOAGULATION BY DABIGATRAN.”