Abstract

Objective :  To find out the role of dyslipedemia as a contributing factor in heart failure cases and study comparatively with the Framingham study (meta analysis).

Methods : This was a cross- sectional study conducted in a tertiary care hospital. The study was approved by the ethics committee of the institute and consent was taken from each participant before enrolling in the study.  A total of 100 cases with signs and symptoms of heart failure (Acute/Acute on Chronic and Chronic heart failure) were included in the study.

Background : The relationship of lipid concentrations to heart failure has been evaluated in a study derived from Framigham Heart study participants.

Keywords: Attribution, Abnormal Lipid

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Introduction

Heart Failure (HF) is a syndrome associated with high morbidity and mortality and enormous economic burden, rendering prevention a priority.1 Elucidating modifiable risk factors for HF will aid the identification and promulgation of prevention strategies. Dyslipidemia is a well-established risk factor for coronary heart disease (CHD)2 and results from clinical trials of lipid-modifying therapy demonstrate that treatment with statins also decreases the incidence of HF.3 This finding suggests that dyslipidemia is a risk factor for HF, although the association may be mediated by the occurrence of myocardial infarction (MI). The Framingham Heart Study detected a direct association between the ratio of total cholesterol to HDL-C and HF risk,5 suggesting that either elevated total cholesterol, or a lowered HDL-C may influence HF risk. Although previous studies assessed the associations between individual lipid measures and HF,4,5 the role of lipids in the incidence of HF in people without pre-existing CHD has not been systematically investigated in a community-based setting in a prospective fashion, with appropriate adjustment for clinical factors (including interim occurrence of MI) that influence HF risk. Elevated low density lipoprotein cholesterol (LDL-C) and decreased high density lipoprotein cholesterol (HDL-C) have been shown to be associated with reduced systolic and diastolic LV function.6,7. Also a previous investigation from the Framingham Heart Study detected a direct association between the ratio of total cholesterol to HDL-C and HF risk,5 suggesting that either elevated total cholesterol, or a lowered HDL-C may influence HF risk. ‘

In our study 100 participants (49% women) patients with unadjusted HF incidence in the low (<160mg/dl) vs. high (≥190mg/dl) non-HDL-C groups was 7.9% and 13.8%, respectively, whereas incidence in the high (≥55 [men], ≥65 [women] mg/dl) vs. low (< 40 [men], <50 [women] mg/dl) HDL-C groups was 6.1% and 12.8%, respectively. In multivariable models, baseline non-HDL-C and HDL-C, carried HF hazards (confidence interval-CI) of 1.19 (1.11–1.27) and 0.82 (0.75–0.90) respectively per standard deviation (SD) increment .Participants with high baseline non-HDL-C and those with low HDL-C experienced a 29% and 40% higher HF risk respectively, compared to those in the desirable categories; the PARs for high non-HDL-C and low HDL-C were 7.5% and 15% respectively.

Figure 1. Relationship of lipid concentration to heart failure cases

Statistical analysis

Population burden of HF secondary to dyslipidemia by calculating category-specific population attributable risk (PAR), as a function of the proportion of cases (Pd) of HF occurring in each category of HDL-C and non-HDL-C and the relative risk (RR – the hazards ratio from the model adjusting for clinical covariates). The formula we used (expressing PAR as a percentage) is : PAR = Pd ([RR-1]/RR) × 100

Hazards ratios are expressed per standard deviation increment in a lipid value (for analyses using lipids as continuous variables), or comparing the non-optimal lipid concentrations to the referent category. A p-value threshold of 0.05 was used to determine statistical significance. All statistical analyses were performed using SAS software version 8.0 (SAS institute, Cary, NC).

Analysis of single base line measurements are based on values obtained at the time of

Hospitalization.

HR = hazard ratio per standard deviation of the in lipid value. 95% CI = 95% of Confidence intervals.

Figure 2. Population attributable risks for major heart failure risk factors:- were calculated from a model that is adjusted for age,sex, body weight,BMI, hypertension (yes/no), smoking (yes/no),and HDL-C (men<40mg/dl,40-54mg/dl,55mg/dl or greater; women<50mg/dl,50-64mg/dl,65mg/dl or greater) and non HDL –C (<160mg/dl, 160-189 mg/dl,190mg/dl or greater) categories

Discussion

Lipids and HF: Comparison with the Published Literature:-

Previous observational studies have addressed associations of lipid measures with incidence of HF. Kannel et al reported that an elevated total/HDL ratio is associated with increased HF risk.5 Another report from the Framingham Heart Study noted an association, albeit of modest magnitude, between total cholesterol and HF risk.22 Elevated triglycerides have been implicated in HF incidence in the elderly.4 One case-control study reported independent associations between decreased HDL-C and elevated triglycerides and dilated cardiomyopathy.23 Ingelsson et al identified decreased HDL-C and an elevated apolipoprotein B/A-1 ratio (the ratio of the main lipoproteins in LDL-C and HDL-C respectively) as independent predictors of HF risk in a prospective community-based study.24 Investigators from the Physician Health Study identified egg consumption (a rich source of cholesterol) as a risk factor for HF.25 Similarly, increased intake of saturated fat was also implicated as a HF risk factor in a report from the Atherosclerosis Risk in Communities study.26 Another prospective study from Uppsala identified metabolic syndrome (typically associated with elevated triglycerides and low HDL-C) as a HF risk factor.27 Prior investigations, however, were limited by lack of systematic exclusion of baseline CHD and did not consistently adjust for a panel of clinical covariates including interim MI. Furthermore, previous studies did not assess the full range of lipid level alterations.

Conclusion

Based on a comprehensive evaluation of lipid concentrations derived from prospective observation of a healthy, free-living sample, we demonstrate that elevated levels of non-HDL-C and decreased levels of HDL-C are associated with increased risk of HF. It is noteworthy that 15% of heart failure cases were attributable to low HDL-C concentrations. The HF risk associated with dyslipidemia appears to be partly independent of the influence of lipids on risk of MI. These findings lend mechanistic support to previous observations of benefit from lipid therapy in reducing HF incidence. Given the high prevalence of dyslipidemia in the community19, our report highlights the possibility of reducing HF burden by targeting abnormal lipid concentrations for treatment.

Figure 3. Base line characteristics of the participants SD=Standard deviation

Reference

  1. Schocken DD, Benjamin EJ, Fonarow GC, Krumholz HM, Levy D, Mensah GA, Narula J, Shor ES, Young JB, Hong Y. Prevention of heart failure: a scientific statement from the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; Functional Genomics and Translational Biology Interdisciplinary Working Group. Circulation. 2008;117:2544–2565. [PubMed] [Google Scholar]
  2. Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT) JAMA. 1986; 256:2823–2828. [PubMed] [Google Scholar]
  3. Martin JH, Krum H. Statins and clinical outcomes in heart failure. Clin Sci (Lond) 2007; 113:119–127. [PubMed] [Google Scholar]
  4. Eriksson H, Svardsudd K, Larsson B, Ohlson LO, Tibblin G, Welin L, Wilhelmsen L. Risk factors for heart failure in the general population: the study of men born in 1913. Eur Heart J. 1989; 10:647–656. [PubMed] [Google Scholar]
  5. Kannel WB, Ho K, Thom T. Changing epidemiological features of cardiac failure. Br Heart J. 1994; 72:S3–S9. [PMC free article] [PubMed] [Google Scholar]
  6. Palmiero P, Maiello M, Passantino A, Antoncecchi E, Deveredicis C, DeFinis A, Ostuni V, Romano E, Mengoli P, Caira D. Correlation between diastolic impairment and lipid metabolism in mild-to-moderate hypertensive postmenopausal women. Am J Hypertens. 2002; 15:615–620. [PubMed] [Google Scholar]
  7. Rietzschel ER, Langlois M, De Buyzere ML, Segers P, De Bacquer D, Bekaert S, Cooman L, Van Oostveldt P, Verdonck P, De Backer GG, Gillebert TC. Oxidized low-density lipoprotein cholesterol is associated with decreases in cardiac function independent of vascular alterations. Hypertension. 2008; 52:535–541. [PubMed] [Google Scholar]
  8. Dawber TR, Meadors GF, Moore FE., Jr Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health Nations Health. 1951; 41:279–281. [PMC free article] [PubMed] [Google Scholar]
  9. Dawber TR, Kannel WB, Lyell LP. An approach to longitudinal studies in a community: the Framingham Study. Ann N Y Acad Sci. 1963; 107:539–556. [PubMed] [Google Scholar]
  10. Kannel WB, Feinleib M, McNamara PM, Garrison RJ, Castelli WP. An investigation of coronary heart disease in families. The Framingham offspring study. Am J Epidemiol. 1979; 110:281–290. [PubMed] [Google Scholar]
  11. Wilson PW, Hoeg JM, D'Agostino RB, Silbershatz H, Belanger AM, Poehlmann H, O'Leary D, Wolf PA. Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis. N Engl J Med. 1997; 337:516–522. [PubMed] [Google Scholar]
  12. McNamara JR, Schaefer EJ. Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin Chim Acta. 1987; 166:1–8. [PubMed] [Google Scholar]
  13. Albers JJ, Warnick GR, Wiebe D, King P, Steiner P, Smith L, Breckenridge C, Chow A, Kuba K, Weidman S, Arnett H, Wood P, Shlagenhaft A. Multi-laboratory comparison of three heparin-Mn2+ precipitation procedures for estimating cholesterol in high-density lipoprotein. Clin Chem. 1978; 24:853–856. [PubMed] [Google Scholar]
  14. Frost PH, Havel RJ. Rationale for use of non-high-density lipoprotein cholesterol rather than low-density lipoprotein cholesterol as a tool for lipoprotein cholesterol screening and assessment of risk and therapy. Am J Cardiol. 1998; 81:26B–31B. [PubMed] [Google Scholar]
  15. Kannel WB, Wolf PA, Garrison RJ, editors. Some Risk Factors Related to the Annual Incidence of Cardiovascular Disease and Death in Pooled Repeated Biennial Measurements. Section 34. The Framingham Heart Study: 30 Year Follow-Up. NIH publication 87-2703. Bethesda, MD: National Institute of Health; 1987. [Google Scholar]
  16. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971; 285:1441–1446. [PubMed] [Google Scholar]
  17. Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 2002. [PubMed] [Google Scholar]
  18. The Lipid Research Clinics Population Studies Data Book: Volume 1. The Prevalence Study; Section II: "Plasma lipids and lipoproteins by age, race, sex and hormone usage 200. [Google Scholar]
  19. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117:e25–e146. [PubMed] [Google Scholar]
  20. Kannel WB, Abbott RD. Incidence and prognosis of unrecognized myocardial infarction. An update on the Framingham study. N Engl J Med. 1984; 311:1144–1147. [PubMed] [Google Scholar]
  21. Sheifer SE, Manolio TA, Gersh BJ. Unrecognized myocardial infarction. Ann Intern Med. 2001; 135:801–811. [PubMed] [Google Scholar]
  22. Kronmal RA, Cain KC, Ye Z, Omenn GS. Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. Arch Intern Med. 1993; 153:1065–1073. [PubMed] [Google Scholar]
  23. Skwarek M, Bilinska ZT, Mazurkiewicz L, Grzybowski J, Kruk M, Kurjata P, Piotrowski W, Ruzyllo W. Significance of dyslipidaemia in patients with heart failure of unexplained aetiology. Kardiol Pol. 2008; 66:515–22, discussion. [PubMed] [Google Scholar]
  24. Ingelsson E, Arnlov J, Sundstrom J, Zethelius B, Vessby B, Lind L. Novel metabolic risk factors for heart failure. J Am Coll Cardiol. 2005; 46:2054–2060. [PubMed] [Google Scholar]
  25. Djousse L, Gaziano JM. Egg consumption and risk of heart failure in the Physicians' Health Study. Circulation. 2008; 117:512–516. [PMC free article] [PubMed] [Google Scholar]
  26. Yamagishi K, Nettleton JA, Folsom AR. Plasma fatty acid composition and incident heart failure in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 2008; 156:965–974. [PMC free article] [PubMed] [Google Scholar]
  27. 28.(Relations of Lipid Concentrations to Heart Failure Incidence: The Framingham Heart Study: Raghava S. Velagaleti, MD, Joseph Massaro, PhD, Ramachandran S. Vasan, MD, Sander J. Robins, MD, William B. Kannel, MD, and Daniel Levy, MD, Published online 2009 Nov 23. doi: 10.1161/CIRCULATIONAHA.109.830984.