A Cross-Sectional Study of the Current Management of Hypertriglyceridemia

Objectives To estimate the prevalence of hypertriglyceridemia (HTG), determine the association between HTG and the risk of ischemic heart disease and major adverse cardiovascular events. Lastly, to assess the management outcomes of HTG in terms of the different drugs in the treatment plan. Methods A retrospective, longitudinal study at a tertiary hospital was conducted. All who came in were screened. Patients with HTG (TAG [triacylglyceride] 2.3 mmol/L) in the last five years were included in the study. The data included the demographic variables, potential causes, and the methods of management. All data were recorded in a standard data collection form and analyzed by an appropriate statistical tool, using the John Macintosh Project (JMP) software version 15 (Cary, NC: SAS Institute Inc.). Results Of 300 patients included, 174 (58.0%) were male, with a mean age of 57.8±13.4 years. Pre-treatment, the mean triglycerides (TG) was 3.2±2.3 mmol/L, low-density lipoprotein (LDL) 2.7±1.3 mmol/L, high-density lipoprotein (HDL) 0.93±0.30 mmol/L, and the total cholesterol (TC)was 5.2±1.3 mmol/L. All the patients have prescribed a statin, 144 (48.0%) received aspirin, six (2.0%) fenofibrate, and three (1.0%) gemfibrozil. At the follow-up, the level of the TG was 2.6±1.3 mmol/L (P=0.001), LDL 2.5±1.2 mmol/L (P=0.006) and total cholesterol (TC) 4.7±1.5 mmol/L (P=0.001). Almost a third (28.2%) developed cardiac complications, five (1.6%) presented with unstable angina, six (2.0%) as non-ST segment elevation myocardial infarction (NSTEMI), three (1.0%) had ST segment elevation myocardial infarction (STEMI), and 19 (6.3%) had heart failure. A small proportion (17.3%) had a percutaneous coronary intervention, 27 (9.0%) had single-vessel disease, 12 (4.0%) two-vessel disease, and 13 (4.3%) three-vessel disease. Conclusions Many physicians do not pay attention to HTG in everyday practice, although HTG contributes significantly to the occurrence of coronary heart disease. In our study, the majority had mixed hyperlipidemia. One-third of patients with high triglycerides developed ischemic heart disease. The use of fenofibrate and gemfibrozil was not high. A low occurrence of pancreatitis was noted in our series.


Introduction
Cardiovascular diseases and atherosclerosis have been associated with low-density lipoprotein cholesterol (LDL-C) levels in the last decade, but growing evidence supports the positive relationship between cardiovascular diseases and high levels of triglycerides (TG) [1]. Severely elevated TG is associated with pancreatitis but other systems may also be affected. TG elevation could be primary or familial or due to a secondary cause, such as uncontrolled diabetes, obesity, or alcohol consumption. A high TG, in many cases, is asymptomatic until it exceeds 500 -1,000 mg/dL (5.7 mmol/L or above) [2]. Recently, TG was considered a major independent risk related to LDL-C or to its lowering therapy [3]. The prevalence of high TG in Saudi Arabia is estimated at 40.3% [4].
It is debatable whether the reduction of TG will prevent cardiovascular risks [5][6]. Our study focused on the association of TG as an independent risk factor for cardiovascular disease (CVD) in Saudi adults. The study also determined the effect of the current management in lowering the level of high TG.

Materials And Methods
This was a retrospective, longitudinal study conducted at a tertiary care center in Saudi Arabia, in the period 2015-2020. The participants were selected consecutively from the hospital's electronic medical record system. All patients aged > 18 years included. Those with incomplete data (42 patients ) were excluded. The study incorporated all the patients with a TG > 2.3 mmol/L over the last five years. The demographic characteristics, including the comorbidities, medication, and complications related to a high TG profile were collected. In total, 300 patients were enrolled in the study. All the desired information was recorded in a standard Excel sheet (Redmond, USA: Microsoft Corporation). Acute pancreatitis was defined by (a) abdominal pain suggestive of pancreatitis, (b) serum amylase or lipase level greater than three times the upper normal value, or (c) characteristic imaging findings of acute pancreatitis. Acute kidney injury was defined by measuring the abrupt (≤48 hours) reduction of kidney function: increased serum creatinine levels 1.5-fold from baseline. Cardiac disease was recorded if the patient had chest pain with ECG changes and rise in troponin, and undergone cardiac catheterization. Death due to a cardiac cause was included as a measured outcome.
This study was approved by the Institutional Review Board of King Abdullah International Medical Research Center. Frequency and percentage were used to describe the categorical variables. The Chi-square or Fisher's exact test was used to compare the categorical data. A p-value of less than 0.05 was considered statistically significant. The data were analyzed using the John Macintosh Project (JMP) software version 15 (Cary, NC: SAS Institute Inc.).

Results
A total of 342 patients were identified as TG >2.3 mmol/l. The sample realized as 300, with a mean age of 57.8±13.4 years. 42 patients were excluded due to incomplete data. More than half (58.0%, n=174) were male. Of the female group, six (2.0%) were pregnant. The mean body mass index (BMI) was 31.1±6.5 kg/m2. A small proportion (4.7%, n=14) had a family history of high TG, 31 (10.3%) were smokers, and 17 (5.7%) were ex-smokers. Only one (0.3%) reported alcohol intake.

Discussion
The association between cardiovascular diseases and atherosclerosis with the blood triglyceride level has been controversial as a risk factor [7,8,9,10]. Elevated TG association with an increased risk of atherosclerotic cardiovascular disease (ASCVD) becomes insignificant after adjusting for non-HDL cholesterol (non-HDL-C), which represents the total concentration of all Apo B-containing lipoproteins [11]. The fibrate lowering of TG reduces the risk of cardiovascular events when measured per unit change of non-HDL-C [12,13]. A systematic review and meta-analysis of observational studies evaluating hypertriglyceridemia (HTG) and LDL cholesterol (LDL-C) levels (hazard ratio 0.8; P=0.025) [14]. However, most studies suggested that hypertriglyceridemia is associated with a substantially increased long-term total mortality and CVD risk. No such data are available in developing countries, including Saudi Arabia.
In our study, the groups with a high TG and TC were similar in terms of gender at the mid-fifties age range. This is comparable with a Turkish report, with a lipid abnormality recorded in 78.7% of men and 80.4% of women, and the highest prevalence in the 46-65 years age group [15].
One-quarter of our population had cardiac disease, all confirmed with coronary angiography. A varying spectrum of the coronary lesions was noted. The prevalence was similar to another study conducted in Riyadh, Saudi Arabia that suggested 20% of their sample had coronary heart disease [16]. The occurrence of the acute coronary syndrome spectrum was low, less than 2%. Reviewing the literature, we only found one case report of acute STEMI complicated by severe HTG [17].
The current study revealed that most of the current lipid therapy achieved the target goal with a significant reduction in the TG, LDL, and TC. A systematic review revealed statin can lower TG level (MD =-0.43; 95% CI: -0.76 to -0.09; Z =2.51; P=0.01) [18]. This effect is more marked with a potent statin. This approach is recommended by the guidelines. Statin treatment is recommended as the first drug of choice to reduce CVD risk in high-risk individuals with HTG ( >2.3 mmol/L or >200 mg/dL) [19] The use of fenofibrate and gemfibrozil was low in the sample, probably due to achieving the target with statins. The use of these two drugs was given class IIb [19]. It is important to stress the role of diet, exercise, and community-based intervention to decrease cardiac risk profile in patients with high TG [20] The study will stimulate additional research in our region and other developing countries, as some of the findings may be related to the sample size.

Conclusions
High triglycerides level is an overlooked factor in the association between lipid parameters and coronary artery disease, which should be managed when evaluating the risk profile of patients. Our study indicated that a high TG presents mostly as chronic heart disease, rarely as an acute coronary syndrome. The current standard lipid therapy is an effective mode of therapy with a low incidence of pancreatitis. In our study, the majority had mixed hyperlipidemia. The use of fenofibrate and gemfibrozil was not high in our series.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. King Abdullah International Medical Research Center issued approval RJ 19/074/J. The study granted approval after full review by the IRB office. No consent is required as the study does not disclose the particpants identification. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.