Prevalence of familial hypercholesterolemia in premature coronary artery disease patients admitted to a tertiary care hospital in North India.

AIMS: The prevalence of premature coronary artery disease (CAD) in India is two to three times more than other ethnic groups. Untreated heterozygous familial hypercholesterolemia (FH) is one of the important causes for premature CAD. As the age advances, these patients without treatment have 100 times increased risk of cardiovascular (CV) mortality resulting from myocardial infarction (MI). Recent evidence suggests that one in 250 individuals may be affected by FH (nearly 40 million people globally). It is indicated that the true global prevalence of FH is underestimated. The true prevalence of FH in India remains unknown. METHODS: A total of 635 patients with premature CAD were assessed for FH using the Dutch Lipid Clinical Network (DLCN) criteria. Based on scores, patients were diagnosed as definite, probable, possible, or no FH. Other CV risk factors known to cause CAD such as smoking, diabetes mellitus, and hypertension were also recorded. RESULTS: Of total 635 patients, 25 (4%) were diagnosed as definite, 70 (11%) as probable, 238 (37%) as possible, and 302 (48%) without FH, suggesting the prevalence of potential (definite + probable) FH of about 15% in the North Indian population. FH is more common in younger patients, and they have lesser incidence of common CV risk factors such as diabetes, hypertension, and smoking than the younger MI patients without FH (26.32% vs.42.59%; 17.89% vs.29.44%; 22.11% vs.40.74%). CONCLUSION: FH prevalence is high among patients with premature CAD admitted to a cardiac unit. To detect patients with FH, routine screening with simple criteria such as family history of premature CAD combined with hypercholesterolemia, and a DLCN criteria score >5 may be effectively used.

To study the effect of high dose Atorvastatin 40mg versus 80mg in patients with dyslipidemia.

OBJECTIVE: Primary objective was to compare the effects of atorvastatin 40mg vs 80mg on LDL-C in Indian patients with atherosclerotic dyslipidemia. Secondary objectives were to compare the effects of atorvastatin 40mg vs 80mg on HDL-C and triglycerides and also comparing of side effects (myopathy, hepatotoxicity and new onset diabetes mellitus) of both doses. METHOD: This Study is A Prospective, randomized, open-label, comparative study. This study was conducted on 240 patients of dyslipidemia (as per ACC/AHA 2013 lipid guidelines) attending the OPD/wards/CCU of department of cardiology, Sir Ganga Ram Hospital. They were randomly divided into 2 groups of 120 each. Group A consisted patients who received Atorvastatin 40mg daily and Group B Atorvastatin 80mg daily. The follow up period was 6 months. RESULTS: At 3 and 6 month follow up, Atorvastatin 40mg leads to mean LDL cholesterol reduction of 47.18±20.81 & 50.03±18.06 respectively. While Atorvastatin 80mg results in LDL reduction as 50.11±15.85 & 52.30±13.72. The comparison between two doses revealed a non-significant difference (p=.118 & p=.149 respectively). At 6 months of follow up, few patients reported myalgia (2 in group A and 7 in Group B). The difference between groups was significant (p=.045). Although none of our patient had significant elevation of CPK. CONCLUSION: This study concluded that both doses of atorvastatin (40 & 80mg) are equally efficacious in improving dyslipidemia but higher dose leads to more incidence of myalgia.

Yoga and meditation in cardiovascular disease.

Yoga is a holistic mind-body intervention aimed at physical, mental, emotional and spiritual well being. Several studies have shown that yoga and/or meditation can control risk factors for cardiovascular disease like hypertension, type II diabetes and insulin resistance, obesity, lipid profile, psychosocial stress and smoking. Some randomized studies suggest that yoga/meditation could retard or even regress early and advanced coronary atherosclerosis. A recent study suggests that transcendental meditation may be extremely useful in secondary prevention of coronary heart disease and may reduce cardiovascular events by 48% over a 5-year period. Another small study suggests that yoga may be helpful in prevention of atrial fibrillation. However, most studies have several limitations like lack of adequate controls, small sample size, inconsistencies in baseline and different methodologies, etc. and therefore large trials with improved methodologies are required to confirm these findings. However, in view of the existing knowledge and yoga being a cost-effective technique without side effects, it appears appropriate to incorporate yoga/meditation for primary and secondary prevention of cardiovascular disease.

Reducing the burden of coronary artery disease in India: challenges and opportunities.

UNLABELLED: Asian Indians--living both in India and abroad--have one of the highest rates of coronary artery disease (CAD) in the world, three times higher than the rates among Caucasians in the United States. The CAD among Indians is usually more aggressive at the time of presentation compared with whites or East Asians. The overall impact is much greater because the CAD in Asian Indians affects the "younger" working population. This kind of disproportionate epidemic among the young Indians is causing tremendous number of work days lost at a time when India is experiencing a dizzying economic boom and needs a healthy populace to sustain this boom. While the mortality and morbidity from CAD has been falling in the western world, it has been climbing to epidemic proportions among the Indian population. Various factors that are thought to contribute to this rising epidemic include urbanization of rural areas, large-scale migration of rural population to urban areas, increase in sedentary lifestyle, abdominal obesity, metabolic syndrome, diabetes, inadequate consumption of fruits and vegetables, increased use of fried, processed and fast foods, tobacco abuse, poor awareness and control of CAD risk factors, unique dyslipidemia (high triglycerides, low HDL-cholesterol levels), and possible genetic predisposition due to lipoprotein (a) [Lp(a)] excess. The effect of established, as well as novel, risk factors is multiplicative, not just additive (total effect>sum of parts). The management would require aggressive individual, societal, and governmental (policy and regulatory) interventions. Indians will require specific lower cut-offs and stricter goals for treatment of various risk factors than is currently recommended for western populations. To this end, the First Indo-US Healthcare Summit was held in New Delhi, India on December 14 and 15, 2007. The participants included representatives from several professional entities including the American Association of Physicians of Indian origin (AAPI), Indian Medical Association (IMA), Medical Council of India (MCI), and Government of India (GOI) with their main objective to address specific issues and provide precise recommendations to implement the prevention of CAD among Indians. The summary of the deliberations by the committee on "CAD among Asian Indians" and the recommendations are presented in this document. OBJECTIVES: Discussion of demographics of CAD in Indians-both in India and abroad, current treatment strategies, primordial, primary, and secondary prevention. Development of specific recommendations for screening, evaluation and management for the prevention of CAD disease epidemic among Asian Indians. Recommendations for improving quality of care through professional, public and private initiatives.

Serum lipid response to introducing ghee as a partial replacement for mustard oil in the diet of healthy young Indians.

Ghee (clarified butter) has generally been assumed to be hypercholesterolaemic on the basis of its composition but there is hardly any study to support or refute the assumption. The present study was conducted on sixty-three healthy, young, physically active adult volunteers (52 male, 11 female). The study design was that of a randomized controlled trial with a parallel design. After a lead-in period of 2 wk, the subjects were randomly divided into two groups, Group A (n = 30; 25 male, 5 female) and Group B (n = 33; 27 male, 6 female). Group A (experimental) consumed for 8 wk a diet in which ghee provided 10% of the energy intake. The only other visible fat in the diet was mustard oil, and total energy from fats was 25% of the energy intake. Group B (control) consumed for 8 wk a similar diet except that all visible fat came from mustard oil. The serum total cholesterol level showed a significant rise in the experimental group at 4 wk; the rise persisted at 8 wk. A similar rise was also seen in HDL cholesterol. Hence the total cholesterol/HDL cholesterol ratio did not show any significant change. In the control group, there was a trend towards a fall in LDL cholesterol but the change was not significant. The study does not indicate any adverse effect of ghee on lipoprotein profile. However, more studies are needed on older subjects, hyperlipidaemic subjects, and on subjects following less healthy lifestyles before the results of this study can be extrapolated to the general population.

Apolipoprotein C3 SstI polymorphism in the risk assessment of CAD.

Various population studies have reported the association of rare S2 allele of apolipoprotein C3 (APOC3) SstI polymorphism with hypertriglyceridemia (HTG) and coronary artery disease (CAD). We were the first to report an association of S2 allele with high triglyceride (TG) levels in healthy volunteers from Northern India. Since HTG is suggested to be a predominant risk factor for CAD among Indians, we have elucidated the relationship of APOC3 SstI polymorphism with the lipid profile and CAD. A total of 158 patients with > or = 70% stenosis in one or more coronary artery (angiographically proven CAD patients), 35 subjects with < 70% stenosis (NCAD) and 151 normal controls (free of heart disease) from Northern plains of India were recruited in the study. DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Lipid profile was estimated by enzymatic kit. We found a strong association of S2 allele with high TG levels, which was more significant in patients. Prevalence of S2 allele in normal controls and CAD patients were comparable, despite the fact that mean TG level was significantly higher in patients. A greater insight into this observation revealed that the prevalence of high TG, if not coupled with other risk factors (like high total cholesterol, low HDL), was comparable in patients and controls. Thus, our study reveals that rare S2 allele may be employed as a susceptibility marker for high TG. However, high TG or S2 allele alone may not contribute to the etiology of CAD.

Effect of pre- and posttreatment of losartan in feline model of myocardial ischemic-reperfusion injury.

This study investigated the differential effect of losartan, an AT1 receptor blocker, when administered in pre- and postischemic phases, on the biochemical, hemodynamic and oxidative stress associated with regional ischemic-reperfusion injury in cat. Losartan (5 microg/kg/min) or normal saline was administered intravenously in open chest barbiturate anesthetized cats, 15 min before and 10 min after the occlusion of the left anterior descending (LAD) coronary artery. The LAD was occluded for 15 min followed by 60 min reperfusion. In the saline treated group, there was significant depression of hemodynamic functions, i.e., mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP) and left ventricular (LV) peak (+/-) dP/dt, along with depletion of adenosine triphosphate (ATP) of the affected myocardium. Oxidative stress during reperfusion injury was evidenced by significant increase in plasma thiobarbituric acid reactive substances (TBARS) accompanied by significant reduction in myocardial superoxide dismutase (SOD) activities. In both treatment groups, losartan caused recovery of all the hemodynamic parameters and repletion of ATP along with no significant change in plasma TBARS and myocardial SOD activity. There was no effect on catalase activity. Results from the study suggest that the effects of pre- and posttreatment of losartan are comparable in functional recovery of the heart from ischemic-reperfusion injury.

The effect of ingestion of egg on the serum lipid profile of healthy young Indians.

Thirty four healthy young volunteers (22 men, 12 women; age 25.7 +/- 5.8 years; BMI 20.8 +/- 2.3 kg/m2) participated in a randomized controlled cross-over trial on the effect of consuming one boiled egg every day for 8 wk on the serum lipid profile. The only significant change after 8 wk of egg consumption was an elevation of the total cholesterol/HDL cholesterol ratio. However, scrutiny of individual responses revealed that twelve of the subjects (10 men, 2 women) had a greater than 15% rise in the LDL cholesterol level after 8 wk of egg consumption. These subjects, considered hyperresponders, showed significant increases (P < 0.025) at both 4 wk and 8 wk after egg consumption in total cholesterol and LDL cholesterol levels, and at 8 wk in total cholesterol/HDL cholesterol ratio. The remaining 22 hyporesponders showed no change in any of the variables measured at 4 wk or 8 wk after egg consumption. In view of the high nutritional value of eggs, a blanket ban on eggs is not justified. However, since up to one-third of the population may be hyperresponders, knowing the response of an individual is important before making the egg a regular item of the diet.

Treatment of stable angina with low dose diltiazem in combination with the metabolic agent trimetazidine.

BACKGROUND: The risk/benefit of moderate to high doses of calcium antagonists in stable angina is uncertain. This study investigates the efficacy and acceptability of low dose diltiazem in combination with trimetazidine for the treatment of stable angina. METHODS: In a 28-day, randomized, double blind study, treatment with 90 mg diltiazem in combination with 60 mg trimetazidine or placebo per day was compared in 50 patients with stable angina. The primary outcomes were time to 1-mm ST segment depression and the Duke treadmill score. RESULTS: Of the 25 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was, in time to 1-mm ST segment depression, 13 (52) versus 5 (20), P<0.05; in the Duke treadmill score, 18 (72) versus 8 (32), P<0.01; and in angina 17 (68) versus 3 (12), P<0.01. Compared to placebo there was an improvement with trimetazidine in mean exercise time to 1-mm ST segment depression of 128 s (95% confidence interval 45.0-208.5; P<0.01); in the mean Duke treadmill score of 57.4% (95% confidence interval 9.9-100; P<0.02); and in mean anginal attacks of 5.1 per week (95% confidence interval, 3.1-7.3, P<0.01). CONCLUSION: The combination of low dose diltiazem with trimetazidine is effective with few side-effects in the symptomatic control of patients with stable angina.

Study of apolipoproteinc3 Sstl polymorphism in healthy volunteers from Northern India.

Several studies including a small case-control (hypertriglyceridemic/normotriglyceridemic individuals) study by us revealed close association between rare S2 allele ofAPOC3 Sstl polymorphism and hypertriglyceridemia. With the understanding that Asian Indians are highly vulnerable to the adverse effects of hypertriglyceridemia, we extended the investigation and studied the frequency distribution of this polymorphism in 216 healthy volunteers from Northern plains of India. We found that more than 50% of the study population had one or two S2 allele. This may suggest that a larger fraction of this population is genetically predisposed to hypertriglyceridemia.

Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians.

BACKGROUND: A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India. METHODS: DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Digested PCR products were run on 3% agarose gel and visualized by ethidium bromide staining. RESULTS: Rare S2 allele was highly prevalent in our study population (0.313) as compared to the Caucasians (0.00-0.11). The genotypic distribution was in agreement with Hardy-Weinberg equilibrium. S2 allele was almost two times more prevalent in the HTG group (N = 34) as compared to NTG group (N = 105) (p = 0.001). Multiple logistic regression revealed S1S2 individuals had age-adjusted odds ratio of 2.43 (95%CI = 0.99-6.01, p = 0.054) and S2S2 had 9.9 (95%CI = 2.66-37.29, p = 0.0006) for developing HTG in comparison to S1S1 genotype. CONCLUSIONS: Our study shows a significant association between rare S2 allele and HTG in Asian Indians.

Coronary angiography using 4 French catheters with power injection: a randomized comparison with 6 French catheters.

BACKGROUND: Coronary angiography using 4 F catheters may reduce access-site complications and enable early ambulation, although earlier studies suggested that the quality of images may be an issue of concern. METHODS AND RESULTS: To ascertain the quality of angiographic images and safety of early ambulation, 500 patients were randomized to coronary angiography with either 4 F or 6 F catheters. Procedural characteristics, angiographic quality scores and results of ambulation were analyzed in the two groups. Patients in the 4 F group were mobilized at 2 hours post-procedure while those in the 6 F group were ambulated at 6 hours. There was no procedure-related complication in either group. The procedure was successfully completed in 250 of 252 patients randomized to the 4 F group. In two patients in the 4 F group, sheaths were upgraded to 6 F to complete the procedure, as difficulty was encountered in hooking the coronary ostium with a 4 F Judkin's catheter. Coronary angiographic quality scores in these two groups were comparable. Angiographic scores for the 4 F and 6 F groups for the left coronary artery averaged 4.45+/-0.5 and 4.58+/-0.3 (p>0.1), respectively. The right coronary artery scores averaged 4.30+/-0.4 and 4.35+/-0.2 (p>0.1) in the 4 F and 6 F groups. Angiographic scores for the left ventricular angiogram averaged 4.22+/-0.1 and 4.44+/-0.3 (p>0.1) in the 4 F and 6 F groups, respectively. None of the angiograms were assigned a score of <3.0 (not diagnostic). The total contrast volume consumed in the two groups was also equivalent. There were no groin-related complications in the 4 F group although these patients were ambulated 2 hours after the procedure. CONCLUSIONS: Coronary angiography performed with a 4 F catheter is a safe and reliable procedure. The quality of image obtained with a 4 F catheter is equivalent to that obtained with a 6 F catheter. Early ambulation at 2 hours is feasible without compromising safety.

Effect of partial replacement of visible fat by ghee (clarified butter) on serum lipid profile.

A randomised controlled trial with a parallel design was conducted on 24 healthy young volunteers who were divided into two groups. After a lead-in period of 2 wk, the experimental group (n = 11; 9 male, 2 female) had for 8 wk a lactovegetarian diet providing about 25% of the energy intake in the form of fat, of which ghee provided 10 en% and the remaining fat energy came from mustard oil and invisible fat. The control group (n = 13; 8 male, 5 female) had a similar diet except that all visible fat was in the form of mustard oil. In neither group was there any significant change in the serum lipid profile at any point in time. At 8 wk, 2 volunteers in the experimental group, and 1 volunteer in the control group had more than 20% rise in serum total cholesterol as compared to their 0 wk values. There was also an appreciable increase in HDL cholesterol at 8 wk in the experimental group, but it was not statistically significant. Consuming ghee at the level of 10 en% in a vegetarian diet generally has no effect on the serum lipid profile of young, healthy, physically active individuals, but a few individuals may respond differently.

Polymorphism (C677T) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene: A preliminary study on north Indian men.

An elevated level of plasma homocysteine, sulfur containing amino acid generated through demethylation of methionine has been widely accepted as a risk factor for cardiovascular disease (CVD). The increase can result from genetic and/or nutrient related disturbances in the remethylation or transsulfuration pathways for homocysteine metabolism. A common mutation (C677T) in the gene encoding for the enzyme 5, 10-methylenetetrahydrofolate reductase (MTHFR) or deficiency of the B vitamins namely folic acid, B(12), B(6) can lead to hyperhomocysteinemia.In the present study, we have investigated the incidence of the (C677T) MTHFR polymorphism in the North Indian males. 141 angiographically proven coronary artery disease (CAD) patients and 55 age and sex matched healthy volunteers were examined for the association between MTHFR gene polymorphism and CAD. The MTHFR genotyping was performed using polymerase chain reaction (PCR) followed by restriction-isotyping with Hinf 1 endonuclease. A trend for higher 'T' allele frequency (0.19) was observed in patients than in controls (0.16). However no significant association was found between C677T mutation and CAD severity. The lack of statistical significance could be due to the small sample size studied. Hence a larger study including various ethnic groups is warranted.

The effect of ingestion of egg on serum lipid profile in healthy young free-living subjects.

Egg is a major source of dietary cholesterol. Previous studies on the effect of egg on serum lipid profile have given conflicting results. Further, the serum lipid response to egg shows marked individual variation. Since the variation is at least partly genetically determined, and the response depends partly on the overall diet, studies on different ethnic groups are important. There is hardly any study on the subject available on Indians. In the present investigation, eighteen healthy young volunteers (7 male, 11 female) on a lacto-vegetarian diet were given one boiled egg per day for 8 wk in a randomized controlled cross-over study. Compared to the values obtained after 8 wk of egg-free period, the mean serum total cholesterol, LDL cholesterol, HDL cholesterol, total cholesterol/HDL ratio, VLDL cholesterol and triglycerides were not significantly different after 8 wk of egg consumption. However, the serum total cholesterol after 4 wk of egg consumption was significantly higher than the control values. Further, seven subjects out of 18 had an appreciable elevation of serum total cholesterol or LDL cholesterol, or both, after 8 wk of egg consumption. The study suggests that in young healthy Indian subjects on a vegetarian diet, consuming one egg per day raises serum cholesterol levels at 4 wk but in the majority baseline values are restored by 8 wk. However, some hyper-responders continue to have elevated serum cholesterol even at 8 wk. Knowing the response of an individual may be important before making egg consumption a regular habit.

Successful inoue balloon valvotomy in a difficult case of mitral stenosis using multiple modifications of technique: alternative method for loop formation of the Inoue balloon catheter.

Transseptal puncture was accomplished with difficulty at an unfavorable site in a case of severe mitral stenosis with distorted atrial and septal anatomy. Septal balloon entrapment could not be avoided during attempts to cross the mitral valve using the standard technique. This problem was circumvented by resorting to the loop method and the left ventricle was entered first with a guidewire, which then supported the balloon catheter. Successful mitral valve dilatation could thus be performed. A simple alternative method that was used to form the Inoue balloon catheter into a loop is also described.

Captopril and its time of administration in myocardial ischaemic-reperfusion injury.

The present study was designed to investigate the role of captopril in an in vivo model of myocardial ischaemic-reperfusion injury with respect to its time of administration. In open-chest pentobarbitone anaesthetized cats, the left anterior descending coronary artery was occluded for 15 min followed by 60 min of reperfusion. Vehicle (saline) or captopril (4 mg kg(-1)) was administered 10 min before instituting ischaemia (pre-treatment) or 5 min before reperfusion (post-treatment). In the vehicle-treated group, ischaemic-reperfusion injury (IRI) was evidenced by enhanced plasma renin activity, depression of global haemodynamic function (mean arterial pressure, left ventricular-end-diastolic-pressure, peak positive and negative dP/dt) along with depletion of myocardial high energy phosphate (HEP) compounds. Oxidant stress in IRI was evidenced by raised levels of myocardial thiobarbituric acid reactive substances (TBARS) and depletion of endogenous myocardial antioxidants (glutathione, superoxide dismutase and catalase). Pre-treatment with captopril prevented (i) loss of myocardial haemodynamic function, (ii) rise in TBARS and (iii) depletion of myocardial HEP compounds. However, in the post-treatment group, only partial recovery of myocardial haemodynamic function, with no significant reduction in TBARS, was observed. Glutathione, superoxide dismutase and catalase were unaffected by either treatment schedules. The results of the present study suggest that captopril is more effective in attenuating ischaemic-reperfusion injury when administered before ischaemia rather than before reperfusion.