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Despite progress in both primary and secondary prevention, cardiovascular diseases (CVD) are still the largest group of ailments contributing to morbidity and mortality worldwide. Atherosclerotic changes, the primary pathological substrate for CVD, are closely related to hypercholesterolemia. Therefore, the treatment of hypercholesterolemia is a key therapeutic strategy for CVD management. Statins, as the gold standard in the treatment of hypercholesterolemia, have shown enhanced cardiac outcomes in many randomized clinical trials. However, often despite the maximum allowed and tolerated dosage of statins, we are not able to reach the target cholesterol levels, and thus patients persist at an increased cardiovascular risk. Recently, most of the large clinical studies in the field of preventive cardiology have focused on proprotein convertase subtilisin kexin type 9 (PCSK9) and its activity regulation. PCSK9 plays an essential role in the metabolism of LDL particles by inhibiting LDL receptor recirculation to the cell surface. Recent studies have shown that inhibition of PCSK9 by the administration of monoclonal antibodies is capable of significantly reducing LDL levels (up to an additional 60%) as well as reducing the incidence of CVD. However, this treatment procedure of administering the anti-PCSK9 antibodies, most frequently two times a month, has its limitations in terms of time, patient adherence, and nevertheless cost. Administration of active vaccination instead of passive immunization with anti-PCSK9 antibodies may be an effective way of controlling blood cholesterol levels. However, clinical data, as well as human testing, are still inadequate. This work aims to provide an overview of PCSK9 vaccines and their potential clinical benefit.

IntroductionRecent evidence shows that pro-inflammatory cytokines may be important in the assessment of severity and prognosis in congestive heart failure (CHF). In the present study, we examine the association of cytokines with causes, grade and prognosis of CHF patients.Subjects and methodsOf 127 patients with CHF, 11 were excluded and the remaining 116 patients with different aetiologies of CHF, and 250 age- and sex-matched control subjects, were evaluated in this case study. Severity of disease based on the New York Heart Association (NYHA) standards, fell within functional classes II to IV. The diagnosis of HF was based on clinical manifestations as well as on echocardiographic heart enlargement. Cytokines were measured by chemiluminescence. Causes of death were assessed based on death certificates. Multivariate logistic regression analysis was used to determine the risk factors of heart failure.ResultsEchocardiographic ejection fraction was 39.1 ± 8.2% (mean ± SD) in the study group indicating class II-IV heart failure. Laboratory data showed increase in biomarkers of oxidative stress, among HF patients compared to healthy subjects. Pro-inflammatory cytokines; IL-6 and TNF-alpha were significantly higher among HF patients compared to healthy subjects. TNF-alpha and IL-6, showed significant increase among patients with CHF due to ischaemic heart disease and cardiomyopathy compared to levels among CHF patients with valvular heart disease and hypertensive heart diseases. The levels of the cytokines were significantly higher among patients with class III and IV heart failure and those who died, compared to patients with class II heart failure. Multivariate logistic regression analysis revealed that CAD, cardiomyopathy, and IL-6 were strongly associated – and low ejection fraction and TNF-alpha – weakly associated with HF. Of 116 patients, 20 (17.2%) died during a follow-up of two years, and the deaths were mainly among NYHA class III and IV patients in whom the cause of CHF was CAD (10.9%) and cardiomyopathy (6.9%) which had greater levels of cytokines.ConclusionsThe findings indicated that pro-inflammatory cytokines may be important indicators of causes, severity of CHF and prognosis among these patients.

IntroductionThe exact causes of death in India are not known because autopsy studies are difficult to conduct due to religious considerations. There are rapid changes in diet and lifestyle amongst social classes causing changes in the pattern of risk factors and mortality. In the present study, we attempt to develop a verbal autopsy questionnaire based on medical records and interview of a family member, for the assessment of causes of death, social class, tobacco consumption and dietary intakes among urban decedents in north India.MethodsFor the period 1999-2001, we studied the randomly selected records of death of 2222 (1385 men and 837 women) decedents, aged 25-64 years, out of 3034 death records overall from the records at the Municipal Corporation, Moradabad. Families of these decedents were contacted individually to find out the causes of death, by scientist-administered, informed-consented, verbal autopsy questionnaire, completed with the help of the spouse and local treating doctor practicing in the appropriate health care region. Clinical data and causes of death were assessed by a questionnaire based on available hospital records and a modified WHO verbal autopsy questionnaire. Dietary intakes of the dead individuals were estimated by finding out the food intake of the spouse from 3-day dietary diaries and by asking probing questions about differences in food intake by the decedents. Tobacco consumption of the victim was studied by a questionnaire administered to family members. Social classes were assessed by a questionnaire based on attributes of per capita income, occupation, education, housing and ownership of consumer luxury items in the household. The diagnoses of overweight and obesity were based on the new WHO and International College of Nutrition criteria.ResultsCardiac diseases (23.4%, n = 520) including coronary artery disease (10%), valvular heart disease (7.2%, n = 160), diabetic heart disease (2.2%, n = 49), sudden cardiac death and inflammatory cardiac disease, each (2.0%, n = 44) were the most common causes of deaths as reported using the modified verbal autopsy questionnaire. Brain diseases including stroke (7.8%, n = 175) and inflammatory brain disease were reported amongst 1.9% (n = 42) victims. Thus, NCDs (37.0%, n = 651); circulatory diseases (31.2%, n = 695) including stroke and cardiac diseases, and malignant neoplasms (5.8%, n = 131) emerged as the most common causes of death. Injury and accidents (14.0%, n = 313) including fi re, falls and poisonings were also common. Miscellaneous causes of death were observed amongst 8.5% (n = 189) of victims. Pregnancy and perinatal causes (0.72%, n = 15) were not commonly recorded in our study. Renal diseases (11.2%, n = 250), pulmonary diseases (22.3%, n = 495) and liver diseases (4.8%, n =107) were also commonly recorded causes of death. It is clear that causes of death related to various body systems can be more accurately assessed by the modified verbal autopsy questionnaire. Circulatory diseases as the cause of mortality were significantly more common among higher social classes (1-3) than in lower social classes (4 and 5) who died more often, due to infections. Death due to coronary disease, stroke, hypertension, diabetes and obesity were significantly more common among higher social classes 1-3 and among victims with higher body mass index (BMI) compared to social class 4 and 5 who had lower BMI.ConclusionsThis study indicates that causes of death, social class, tobacco and dietary intakes, can be accurately assessed by a modified verbal autopsy questionnaire based on medical records and by interview of family members. Circulatory diseases, injury-accidents and malignant diseases have become the major causes of death in India, apart from infections.

BackgroundThere are few studies detailing the prevalence of prehypertension and hypertension in India.MethodsMen and women, over 25 years of age were included. After completion of a dietitian-administered questionnaire followed evaluation by a physician, physical examination and blood pressure measurement. Cross-sectional survey screened 6940 subjects, (3507 men (M), 3433 women (W): 1993-96) from cities located in five corners of India (Kolkata, n = 900; Nagpur, n = 894; Mumbai, n = 1542; Thiruanantpuram, n = 1602; Moradabad, n = 2002). Prehypertension (BP 130-139/85-89 mm Hg) and hypertension (BP ≥ 140/90 mm Hg) were diagnosed according to the European Society of Cardiology criteria.ResultsPrevalence of prehypertension and hypertension, respectively, was significantly greater in South India (Trivandrum: W 31.5; 31.9%; M 35.1; 35.5%) and West India (Mumbai: W 30.0; 29.1%; M 34.7; 35.6%) compared to North India (Moradabad: W 24.6; 24.5%; M 26.7; 27.0%) and East India (Kolkata: W 20.9; 22.4%; M 23.5; 24.0%). Subjects with prehypertension and hypertension were older, had a higher BMI, central obesity and a sedentary lifestyle. They had a higher salt and alcohol intake, with greater oral contraceptive usage (W). Multivariable logistic regression analysis revealed strong positive associations of hypertension with age, central obesity, BMI, sedentary lifestyle, salt and alcohol intake and oral contraceptive usage (W). Fruit, vegetable and legume intake showed inverse associations, tobacco intake showed none. One in four with hypertension was aware of their diagnosis and of those receiving treatment, one in three had well-controlled hypertension.ConclusionsThere is little awareness that prehypertension and hypertension are public health issues in India. Ageing population, central obesity, sedentary lifestyle, excessive salt and alcohol, lower fruit, vegetable and legumes intake increase risk for blood pressure elevation.

Introduction—There is evidence that both carnitine and coenzyme Q10 (Co Q), which are important for the functioning of myocardial mitochondria, are deficient in patients with congestive heart failure, in association with increased pro-inflammatory cytokines. It is possible that supplementation with ubiquinol and L-carnitine may protect these patients by decreasing inflammation.Subjects and methods— In a randomized, double-blind, placebo-controlled trial, the effects of carni Q-gel (2250 mg/d L-carnitine and 270 mg/d hydrosoluble ubiquinol) were examined for 12 weeks.Thirty-one patients with heart failure received intervention (group A) and another 31 patients served as controls (group B). Serum levels of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and IL-10 could be studied among 29 patients in each group. Statistical analysis was conducted by analysis of variance and chi square test.Results— Echocardiography ejection fractions were lower at baseline (38.8 + 7.6 vs. 39.3 + 6.7% in the intervention and control groups, respectively) among both group of patients, indicating class II-IV heart failure. Serum concentration of interleukin-6 (IL-6), a pro-inflammatory cytokine, was high (18.7 ± 5.8 vs. 15.0 + 3.3 pg/ml, normal 0.0-3.9) and IL-10 (anti-inflammatory) was normal (3.4 ± 1.5 vs. 2.9 ± 1.0 pg/ml, the normal range is 1.5-3.1 pg/ml) in both groups at baseline.After 12 weeks, there was a marked reduction in IL-6 in the intervention group without such changes in the control group (7.6 ± 1.5 vs. 11.4 ± 2.5 pg/ml, P< 0.01. IL-10 showed only the non-significant decrease in both groups from the baseline levels (3.2 ± 1.0 vs. 2.8 ± 0.9 pg/ml).TNF-alpha, which was comparable at baseline (17.6 ± 4.3 vs. 20.0 ± 5.3 pg/ml), also showed a greater decline in the carni Q-gel group compared to the placebo group (12.5 ± 3.3 vs. 17.2 ± 3.2 pg/ml, P< 0.05). Baseline serum CoQ levels (0.21 ± 0.11 vs. 0.19 ± 0.10 μg/ml) were low; however, after 12 weeks, serum CoQ showed a significant increase in the carni Q-gel group as compared to the control group (2.7 ± 1.2 and 0.76 ± 0.14 μg/ml, respectively). After 12 weeks of treatment, the quality of life visual analogous scale revealed that dyspnoea, palpitation and fatigue, (NYHA class II-III-IV), which were present at rest in all patients at baseline, showed beneficial effects in the intervention group compared to the placebo group. The six-minute walk test showed that there was a significant greater benefit in walking, from the baseline distance in the intervention group (208 ± 15.8 vs. 281 ± 20.6 metres, P<0.02) compared to the placebo group (218.4 ± 17.6 vs. 260.7 ± 19.3 metres, P < 0.05). The symptom scale indicated that the majority of patients showed improvement in the intervention group compared to the control group (28 vs. 16 patients, respectively, P< 0.05).Three patients in the intervention group had nausea and vomiting, which were controlled with symptomatic treatment.Conclusions— These findings indicate that treatment with ubiquinol + L-carnitine can cause a significant reduction in the pro-inflammatory cytokines that are neurohumoural precursors related to sympathetic and parasympathetic activity, which is impaired in patients with heart failure. There was no adverse effect on IL-10.There was a significant improvement in quality of life as well as decrease in NYHA-defined heart failure.