Prevalence of Diastolic Dysfunction in Non Diabetic Patients of Metabolic Syndrome

Background :The purpose of the present study was to study the prevalence of metabolic syndrome in non diabetic patients of metabolic syndrome Materials and Methods: 100 patients of non diabetic metabolic syndrome were screened using 2-D Echocardiogram. Results: 34% of non diabetic patients of metabolic syndrome had diastolic dysfunction, with no association found between the components of metabolic syndrome and diastolic dysfunction. There was a strong correlation between a past history of hypertension and dyslipidemia with diastolic dysfunction. Conclusion: Our ndings suggest that long standing metabolic syndrome is a risk factor for diastolic dysfunction, rather than short term elevation of the metabolic syndrome parameters. Also it is likely that Diabetes and Prediabetes itself is responsible for most of the diastolic dysfunction that is seen in metabolic syndrome


Introduction
The term metabolic syndrome was coined by Haller in1977.Also known as Syndrome X its main features are central obesity, dyslipidemia, hypertension and hyperglycemia. The cardiovascular risk factors comprising the metabolic syndrome are now considered the driving force behind the new cardiovascular disease (CVD) epidemic (1).
Presence of diastolic dysfunction (DD) in metabolic syndrome (MS) has been seen in several studies. Its incidence appear to range between 20-40% in the western population (1,2).However, several south east Asian studies show a much higher percentage of DD in MS, up to 73% (1,3,4).
These alarming numbers maybe due to the higher risk that Asian Indians have for coronary artery disease (CAD) because of their unique lipid pro le. The dyslipidemia in South Asians is most importantly characterized by elevated levels of triglycerides, low levels of HDL-C, elevated Lp(a) levels, and a higher atherogenic particle burden despite relatively normal LDL-C levels. HDL particles appear to be smaller, dysfunctional, and proatherogenic in South Asians, thus leading to earlier CAD independent of other metabolic risk actors (5). Diastolic dysfunction occurs early in the ischemic cascade. (6). Thus it appears reasonable to postulate that the higher incidence of DD in MS in this region might be due to the higher incidence of early CAD in South Asians. In this context it is interesting to note that low HDL is the only variable not signi cantly associated with DD in a study from Serbia (7) while Khan et al, reporting on a similar study from Pakistan, showed a very strong association between low HDL and DD (4). DD is characterized by left ventricular (LV) stiffness and impaired relaxation due to LV myocardial brosis. Several mechanisms are responsible for the same, from the cardiac remodeling seen in advanced hypertensive and diabetic patients to the insulin resistance and in ammation seen in asymptomatic patients of metabolic syndrome (8).DD accounts for 50% of all admissions for acute heart failure (9) and has a cardiovascular mortality similar to systolic heart failure (10).For the asymptomatic patient, impaired exercise capacity limits activities of daily life. (11). Grade 1 DD causes 2 fold increase in all cause and cardiac mortality (12,13).It is now imperitive,from a medical and economic perspective to identify the patients of DD While studies have been performed which show association between various components of MS with DD, with clear evidence that worsening grades of diastolic dysfunction are associated with increasing burden of metabolic syndrome ( 4,8), the contribution of each variable towards DD is not clear. Central obesity (de ned as waist circumference of greater than or equal to 90 cm in men and 80 cm in women) Plus any two out of three of the following i. TG Levels > 150 mg/dl or speci c treatment for this lipid abnormality ii. HDL < 40 mg/dl in males or < 50 mg/dl in females iii. Systolic BP greater than or equal to 130 mm Hg and diastolic BP greater than or equal to 85 mm Hg or previously diagnosed hypertension Patients with established diabetes mellitus or on treatment for same as well as impaired fasting glucose were excluded from the study as were patients with any myocardial disease other than diastolic dysfunction.
A total of 100 patients of non-diabetic MS were selected. Eligible patients were enrolled into the study after taking informed consent at visit 1. A detailed history and physical examination was done which included anthropometry, blood pressure measurement, signs and symptoms of diastolic heart failure.
Echocardiogram was performed by Tissue Doppler Imaging and the parameters were noted. Chi square test was used for determination of statistical signi cance

Results
Out of hundred patients 30 were females and 70 were males. The minimum age was 21 years and maximum of 60 years with a mean of 43.23+/-8.75.Weight ranged between 58 kgs to 117 kgs with a mean of 78.65+/-12. 17 patients had a normal BMI (b/w 18-24.99kg/m2),49 patients were overweight (BMI b/w 25-29.99 kg/m2) and 33 patients were obese( BMI >30 kg/m2) 42 out of hundred patients had a past history of hypertension, out of the rest 15 patients were normotensive at the time of examination and the remaining 43 had never been diagnosed with hypertension but had systolic and/or diastolic blood pressures elevated as per the IDF criterion.  There was no correlation found between the other components of metabolic syndrome and diastolic dysfunction.

Discussion
Our study showed a prevalence of 34% DD in non-diabetic patients of MS. This is signi cantly lower than the prevalence seen in other studies from the Indian subcontinent (1,3,4). All of these studies were done in diabetic MS patients. A study by Dinh et al in 2011 was done on 166 patients, dividing them into 3 groups; Impaired Glucose Tolerance (IGT), Diabetic and Non Diabetic group (NGT). The prevalence of DD was 81% in the IGT group, 96% in the diabetic group and 61% in the NGT group, respectively (P< 0.001). Twelve percent of subjects with NGT, 28% of patients with IGT and 35% of the diabetic group were classi ed as having a more severe form of LVDD (14).
Given the high prevalence of DD in diabetic patients, with some studies showing a prevalence up to 100% (15), it would be tempting to conclude that Diabetes is the predominant contributor to DD in MS.
The review of literature places the prevalence of DD in hypertensive patients in a variable range. While in the Caucasian population, the incidence appears to be in the range of 40-45% (16), the prevalence in South East Asian and African populations are higher. Independent small sample size studies from India report the prevalence of DD in hypertensives to be between 55-70% (17,18) while a Nigerian population study placed the incidence of DD in hypertensive patients at 82% (19). The E-ECHOES study done in the United Kingdom on hypertensive patients of South East Asian ethnicity put the prevalence at 73%,which was comparable to that seen in the African-Caribbean population (72%).However, the parameters of DD were worse in the South East Asian group translating to worse clinical outcomes. (20) In our study 42 patients had past history of hypertension, 57% of whom had DD. 43 were newly diagnosed,20 % of whom had DD. There are con icting reports regarding gender distribution of DD in MS ( 21). Our study did not reveal any gender inequality which is similar to several other studies ( 17,18) MS is a complex constellation of various diseases which is greater than the sum of its whole. How the components interact with each other and whether one component is more important than others, is a question which has not been answered yet. It would require studies both long term and well de ned before we come close to the answer. While the signi cantly lower prevalence of DD in our study after excluding diabetics, certainly appears to suggest that diabetes is a major contributor to DD in MS, more such studies are required before we can reach a conclusion. Limitations: One of the major limitations of our study is the comparatively younger group of patients studied. The average age of our patients was 43years. Since age has a well known association with DD in MS (17,18) it is a possibility that the lower prevalence of DD in our study could be explained by this.

Conclusion
1) The prevalence of diastolic dysfunction was found to be 34% in the patients of nondiabetic/prediabetic metabolic syndrome,which is less than that found in the diabetic metabolic syndrome group.
2) No correlation was found between parameters of diastolic dysfunction and components of metabolic syndrome. There was signi cant correlation between past history of dyslipidemia and hypertension with diastolic dysfunction indicating that prolonged exposure to metabolic syndrome parameters are responsible for the development of diastolic dysfunction. K.K collected the material. P.A analysed the data. K.K and P.A wrote the manuscript in collaboration.