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October 2016, Volume 66, Issue 10

Original Article

The impact of hypertension on lipid parameters in type 2 diabetes

Abdul Rehman Arshad  ( Department of Medicine, Mountain Medical Battalion, Pakistan. )
Hamid Nawaz Tipu  ( Department of Pathology, Combined Military Hospital, Khuzdar, Pakistan. )
Athar Iqbal Paracha  ( Department of Medicine, Mountain Medical Battalion, Pakistan. )


Objective: To study the effect of hypertension on lipid levels in patients with type 2 diabetes mellitus.
Methods: This prospective, observational study was conducted at 1 Mountain Medical Battalion, Bagh, Azad Kashmir, from May 2012 to April 2015, and comprised adult type 2 diabetics. Patients already on lipid-lowering agents, hypothyroidism, nephrotic syndrome, unwilling patients and those who had serum triglycerides>4.5mmol/l were excluded. Blood pressure was measured twice in sitting position. Amongst hypertensive patients, blood pressure <140/90mmHg reflected good control. Serum total cholesterol, triglyceride and high-density lipoproteins were measured using enzymatic calorimetric method. Friedewald equation was used to calculate low-density lipoprotein levels.Subjects were divided into three groups: those without hypertension; those with hypertension but good blood pressure control; and hypertensives with poor blood pressure control. SPSS 20 was used for data analysis.
Results: Of the 322 patients, 129(40.06%) were women and 193(59.94%) were men. The overall mean age was 51.42±10.93 years. Hypertension was seen in 144(44.72%) patients. Blood pressure was well controlled in 46(31.94%) hypertensive patients. Among patients without hypertension and those with good or poorly controlled blood pressure, the mean values for serum total cholesterol were 181.08± 32.05, 186.87± 39.00, 185.33± 35.55 mg/dl, triglycerides were 172.57±80.53, 187.61±81.42, 183.19±74.34 mg/dl, high-density lipoproteins were 40.54±12.36, 37.06±8.80, 40.15±12.35 mg/dl and low-density lipoproteins were 105.79±29.73, 110.81±31.66, 106.56±35.16 mg/dl. The number of patients with abnormalities of total cholesterol was 44(26.83%), 13(28.26%), 33(29.46%), triglycerides was 83(50.61%), 30(65.22%), 66(58.93%), high-density lipoproteins was 119(72.56%), 39(84.78%), 93(83.04%) and low-density lipoproteins was 90(54.88%), 29(63.04%) and 59(52.68%), respectively.
Conclusion: Hypertension did not worsen diabetic dyslipidaemia.
Keywords: Dyslipidaemia, Metabolic syndrome X, Risk factors, Pakistan. (JPMA 66: 1262; 2016)

The prevalence of coronary heart disease (CHD) is continuously increasing. Nearly 27% of Pakistanis aged 40 years or above have CHD.1 Hypertension and dyslipidaemia are two of the several major risk factors. The relationship between dyslipidaemia and hypertension is complex. It is believed that dyslipidaemia may lead to the development of hypertension by causing endothelial dysfunction.2 Moreover, the co-existence of these two risk factors exerts more than an additive impact on the vascular endothelium, resulting in heightened atherosclerosis and thus CHD.3

Type 2 diabetes mellitus (T2DM) is another important risk factor for CHD, often labelled as a CHD risk equivalent. In patients with diabetes, hypertension is often seen as a component of the well-known metabolic syndrome. High blood pressure (BP) portends an increased risk of diabetic micro- as well as macrovascular complications. Co-existent hypertension increases mortality by 7.2 times in diabetics.4 In such patients, targeting hypertension and dyslipidaemia reduces cardiovascular risk beyond the level achieved by lowering blood glucose levels only.5 It has even been suggested that controlling blood pressure with intensive pharmacological treatment may be even more important in reducing cardiovascular risk than blood glucose control.6

Both diabetes and hypertension are known to be associated with lipid abnormalities. Almost 50% diabetics have dyslipidaemia.7 This is characterised by elevated plasma triglycerides (TG) levels, low high-density lipoproteins (HDL) cholesterol levels and increased concentration of small dense low-density lipoproteins (LDL) cholesterol. Similarly, dyslipidaemia has been reported in 50% to 80% of hypertensive patients.8 Given the effects of both these disorders on lipid parameters individually, it may be presumed that the impact of co-existent diseases would be far greater. However, this has not been studied adequately on our local population. The current study was carried out to determine the effect of hypertension on lipid levels in patients with T2DM.

Patients and Methods
This prospective, observational study was carried out at 1 Mountain Medical Battalion, Bagh, Azad Kashmir, from May 2012 to April 2015. Approval of the research protocol was obtained from the institutional ethics review committee. Patients with T2DM, aged 30 or above, presenting to medical outdoor clinic for the first time during the study period were analysed for eligibility. Patients already on lipid-lowering agents, had hypothyroidism, nephrotic syndrome, or serum triglyceride (TG) >398 mg/dl or those who were unwilling to participate were excluded. All those fulfilling the selection criteria were enrolled after obtaining informed written consent from them. Demographic data was noted down.

History of hypertension as well as the use of any antihypertensive drugs was obtained. Any of these two features was used to define essential hypertension. Blood pressure was measured twice in sitting position with a mercurial sphygmomanometer using the standard technique and mean value was calculated. Blood pressure <140/90mmHg reflected good control of hypertension. Height and weight were recorded to calculate body mass index (BMI). Waist circumference was also measured at the level of iliac crest. Venous whole blood samples were collected after 12 hours\\\' fast for estimation of serum total cholesterol, TG and HDL cholesterol with Merck Microlab-300 Automated Clinical Chemistry Analyser using enzymatic calorimetric method. Friedewald equation was used to calculate LDL cholesterol levels. Upper limits of normal level for different lipid fractions were taken as: total cholesterol= 200.00 mg/dl, TG= 150 mg/dl, LDL cholesterol= 100mg/dl. HDL cholestrol was considered abnormal if it was <40mg/dl in men and <50mg/dl in women.

SPSS 20 was used for data analysis. Patients with diabetes were divided into three groups: those without hypertension, those with good control of blood pressure and those with poor control of blood pressure. Means of the different lipid fractions were compared between the three groups using one- way analysis of variance (ANOVA). Proportions of patients with abnormalities in lipid fractions were compared using chi-square test. A p- value of <0.05 was considered significant.

Of the 322 patients, 129(40.06%) were women and 193(59.94%) were men. The overall mean age was 51.42±10.93 years. Hypertension was seen in 144(44.72%) patients, 46(31.94%) of whom had a good control of blood pressure; the remaining 178(55.28%) patients did not have hypertension (p=0.008). Moreover, 28(8.7%) of the participants were smokers. The overall mean BMI was 26.17±4.78 kg/m2 and waist circumference was 99.10±11.17 cm. The mean systolic and diastolic BP values were 140.51±26.37 mmHg and 85.68±11.20 mmHg (Table-1)

Of those who had hypertension, the condition of 46(31.94%) was well controlled while that of 98(68.05%) was poorly controlled. The mean serum total cholesterol was 181.08± 32.05mg/dl among patients without hypertension, 186.87± 39.00mg/dl among those with well-controlled hypertension and 185.33± 35.55mg/dl among those with poorly controlled hypertension (p=0.480). The mean serum TG level was 172.57± 80.53, 187.61± 81.42 and 183.19± 74.34 mg/dl (p=0.376) in the three groups. The mean serum HDL and LDL levels were 40.54±12.36 and 105.79±29.73 mg/dl respectively, among patients who had hypertension; 37.06±8.80 and 110.81±31.66 mg/dl among those with well-controlled hypertension; and 40.15±12.35 and 106.56±35.16 mg/dl among those with poorly controlled hypertension (Table-2)

Moreover, 44(26.83%) patients who had diabetes without hypertension, 13(28.26%) with well-controlled hypertension and 33(29.46%) with poorly controlled hypertension had abnormal serum total cholesterol level (p=0.890). The number of participants who had abnormal serum TG level was 83(50.61%), 30(65.22%) and 66(58.93%) in the three groups, respectively (p=0.144). Besides, abnormal serum HDL level was seen in 119(72.56%) patients in the first group, 39(84.78%) in the second and 93(83.04%) in the third (p=0.058), whereas 90(54.88%), 29(63.04%) and 59(52.68%) patients had abnormal LDL level (p=0.487).
The number of patients with abnormalities of different lipid fractions were similar in the three groups (Table-3)

Atherosclerosis occurs at a faster rate in diabetic patients. Coronary arteries are an important site, and thus these patients are more prone to developing CHD. Hypertension frequently co-exists with diabetes. In an earlier study, we found that 40% of diabetic patients were hypertensive as well.9 This association adds to the CHD risk. Indeed, lowering blood pressure in patients with diabetes can reduce overall mortality as well as deaths from cardiovascular events and stroke.10

The main finding of this study is that co-existent hypertension does not worsen dyslipidaemia in patients with T2DM. Our results are in keeping with the results of a study done by Tedesco et al.11 There was no significant difference in total cholesterol, TG and HDL levels amongst hypertensive and normotensive diabetics. Similarly, a study done on Nigerians concluded that concurrent hypertension and T2DM does not result in a more severe dyslipidaemia than when either of the two conditions occurs alone.12 Proportions ofdiabetic patients with dyslipidaemia were the same in hypertensive and normotensive groups (82.8% vs. 81.5%) in a study done in India.13
Contrasting results have also been reported insome previous studies. Prevalence of dyslipidaemia was higher amongst hypertensive diabetics from Ghana when compared to those without hypertension.14 Amongst a Pakistani diabetic cohort, patients with hypertension had significantly higher non-HDL-C and lower HDL-C in contrast to normotensive patients.15 In a study done in Nigeria, hypertensive diabetics had higher serum total cholesterol, TG and LDL-C as well as lower HDL-C as compared to normotensive diabetics.16 A study done in Macedonia revealed that diabetic hypertensive patients with good control of blood pressure had lower serum total cholesterol, TG, LDL-C, and higher HDL-C, as compared to those having uncontrolled blood pressures.17
Many studies have also reported variable effects of hypertension on different lipid fractions in diabetic patients. Alatab et al. found higher serum LDL-C and total cholesterol levels in hypertensive diabetics from Iran as compared to normotensive diabetics, but the difference in TG and HDL was not statistically significant.18 In an Indian study done by Salman et al., HDL was lower and TG higher but hypertension did not affect total cholesterol and LDL levels.19 Total cholesterol and LDL were higher in hypertensive diabetics, as compared to normotensive diabetics, but TG levels were the same in the two groups in a study done on an African population.20 Similarly, in a Bangladesh study, total cholesterol and LDL-C were found to be higher in hypertensive diabeticsbut there were no differences in levels of HDL and TG.21 However, the results of that study should be interpreted cautiously because of the very small sample size that did not provide adequate power to assess the differences.

Another important finding of the current study is the absence of improvement in lipid parameters with good control of blood pressure. This is in contrast to the Spanish multicentre LIPICAP-PA study where LDL-C control was better in those with good control of blood pressure (43% vs. 22.4%)22 Conflicting results may partially be attributable to a shortcoming of our study design. In this cross-sectional study, control of blood pressure was assessed on the basis of readings taken on a single day only. This information might not be a totally reliable marker of control in the longer run. Nevertheless, since controlling blood pressure alone did not improve lipid profile amongst our patients, additional measures including dietary and pharmacological treatment are required to lower lipids. Use of statins is all the more important because they have antihypertensive effects as well.23

The main strength of this study is the inclusion of all patients satisfying the selection criteria, so that the results are truly reflective of patient population visiting this healthcare set-up. Smoking modifies serum lipid levels, may lead to insulin resistance and can lower serum HDL-C levels.24 In our study, a greater proportion of normotensive patients were current smokers as compared to hypertensive patients. This factor could not be taken care of. There are a few other limitations of this study. We did not study the influence on other confounding factors such as physical activity, dietary habits, oral hypoglycaemic agents and antihypertensive medications on lipid parameters in either of the two groups.

Hypertension super-imposed on diabetes did not aggravate dyslipidaemia seen with diabetes alone.

We are grateful to laboratory technicians Mr. Irshad, Mr. Muhammad Sajid and Mr. Shahzad Mahmood for analysing the serum samples.

Disclaimer: None.

Conflict of Interest: None.

Source of Funding: None.

1.Jafar TH, Jafary FH, Jessani S, Chaturvedi N. Heart disease epidemic in Pakistan: women and men at equal risk. Am Heart J 2005; 150:221-6.
2.Halperin RO, Sesso HD, Ma J, Buring JE, Stampfer MJ, Gaziano JM. Dyslipidemia and the risk of incident hypertension in men. Hypertension 2006; 47:45-50.
3.Dalal JJ, Padmanabhan TN, Jain P, Patil S, Vasnawala H, Gulati A. LIPITENSION: interplay between dyslipidemia and hypertension. Indian J Endocrinol Metab 2012; 16:240-5.
4.Bakris GL, Sowers JR. American Society of Hypertension Writing Group. ASH position paper: treatment of hypertension in patients with diabetes- an update. J Clin Hypertens (Greenwich) 2008; 10:707-13; discussion 714-5.
5.Dokken BB. The pathophysiology of cardiovascular disease and diabetes: beyond blood pressure and lipids. Diabetes Spectr 2008; 21:160-5.
6.McGill JB. Reexamining misconceptions about ?-blockers in patients with diabetes. Clin Diabetes 2009; 27:36-46.
7.Vijayaraghavan K. Treatment of dyslipidemia in patients with type 2 diabetes. Lipids Health Dis 2010; 9:144.
8.O\\\'Meara JG, Kardia SR, Armon JJ, Brown C, Boerwinkle E, Turner ST. Ethnic and sex differences in the prevalence, treatment, and control of dyslipidemia among hypertensive adults in the GENOA study. Arch Intern Med 2004; 164:1313-8.
9.Arshad AR. Control of blood pressure in hypertensive patients with diabetes mellitus type 2. Pak Heart J 2014; 47:78-83.
10.Mohan V, Seedat YK, Pradeepa R. The rising burden of diabetes and hypertension in Southeast Asian and African regions: need for effective strategies for prevention and control in primary health care settings. Int J Hypertens 2013; 2013:409083.
11.Tedesco MA, Natale F, Di Salvo G, Caputo S, Capasso M, Calabró R. Effects of coexisting hypertension and type II diabetes mellitus on arterial stiffness. J Hum Hypertens 2004; 18:469-73.
12.Isezuo SA, Badung SL, Omotoso AB. Comparative analysis of lipid profiles among patients with type 2 diabetes mellitus, hypertension and concurrent type 2 diabetes, and hypertension: a view of metabolic syndrome. J Natl Med Assoc 2003; 95:328-34.
13.Pandya H, Lakhani JD, Dadhania J, Trivedi A. The prevalence and pattern of dyslipidemia among type 2 diabetic patients at rural based hospital in Gujarat, India. Indian J ClinPrac 2012; 22:36-44.
14.AdinorteyMB, Gyan BE, Adjimani J, Nyarko P, Sarpong C, Tsikata FY, et al. Dyslipidemia associated with type 2 diabetes with micro and macrovascular complications among Ghanaians. Indian J Clin Biochem 2011; 26:261-8.
15.Abbasi MA, Hafeezullah, Shah NA, Abro A, Sammo JA. Non high density lipoprotein cholesterol in type 2 diabetes mellitus. Pak J Physiol 2007; 3:40-43.
16.Idogun ES, Unuigbe EI, Ogunro PS, Akinola OT, Famodu AA. Assessment of serum lipids in Nigerians with type 2 diabetes mellitus complications. Pak J Med Sci 2007; 23:708-12.
17.Jani Y, Kamberi A, Ferati F, Rexhepi A, Pocesta B, Orovcanec N, et al. Influence of dyslipidemia in control of arterial hypertension among type-2 diabetics in the western region of the Republic of Macedonia. Am J Cardiovasc Dis 2014; 4:58-69.
18.Alatab S, Fakhrzadeh H, Sharifi F, Mostashfi A, Mirarefin M, Badamchizadeh Z, et al. Impact of hypertension on various markers of subclinical atherosclerosis in early type 2 diabetes. J Diabetes Metab Disord 2014; 13:24.
19.Salman M, Dasgupta S, D\\\'Souza CJM, Xaviour D, Raviprasad BV, Rao J, et al. Impact of hypertension on type 2 diabetes in Mysore population of South India. Int J Clin Med 2013; 4:561-70.
20.Oyelola OO, Ajayi AA, Babalola RO, Stein EA. Plasma lipids, lipoproteins, and apolipoproteins in Nigerian diabetes mellitus, essential hypertension, and hypertensive-diabetic patients. J Natl Med Assoc 1995; 87:113-8.
21.Alam SM, Ali S, Khalil M, Deb K, Ahmed A, Akhter K. Serum lipid profile in hypertensive and normotensive type II diabetes mellitus patients--a comparative study. Mymensingh Med J 2003; 12:13-6.
22.Rodríguez-Roca GC, Alonso-Moreno FJ, Barrios V, LlisterriJL, Lou S, Matalí A, Banegas JR, etal. Cardiovascular; Groupd de Hipertensión Arterial de la Sociedad Española. [Blood pressure findings in Spanish dyslipidemic primary care patients. LIPICAP-PA Study]. Rev Esp Cardiol 2007; 60:825-32. Spanish.
23.Correa V Jr, Fuchs FD, Moreira LB, Gerhardt M, Fuchs SC, Sloczinski CR, et al. Blood pressure lowering effect of simvastatin: a placebo-controlled randomized clinical trial with 24-h ambulatory bood pressure monitoring. J Hum Hypertens 2014; 28:62-7.
24.Erem C, Hacihasanoglu A, Deger O, Kocak M, Topbas M. Prevalence of dyslipidemia and associated risk factors among Turkish adults: Trabzon lipid study. Endocrine 2008; 34:36-51.

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