A 57-year-old African-American male patient with a history of nephrectomy and dyslipidemia was seen in the outpatient department for his annual checkup. The patient has a history of exceptionally high levels of HDL cholesterol without any symptoms of dyslipidemia. Further examination revealed that his high-density lipoprotein level was once more abnormally high (199 mg/dL).

High Total cholesterol levels are a biomarker associated with an increased risk of coronary heart disease and High‐density lipoprotein cholesterol is a biomarker inversely associated with an increased risk of Coronary Heart Disease (CHD) events. It is of considerable value in assessing patients’ coronary artery disease risk. A 2009 meta‐analysis of 108 randomized trials involving nearly 300 000 patients at risk of cardiovascular events found no association between treatment‐induced increases in HDL cholesterol with risk ratios for CHD deaths, CHD events or total deaths after adjustment for changes in Low‐Density Lipoprotein (LDL) cholesterol [1].

High‐density lipoprotein is a complex circulating particle with many subspecies that vary in lipid and protein composition [2]. Cholesterol is a major component of the particle and the amount of cholesterol contained in HDL particles can be directly measured; it is referred to as HDL cholesterol. In clinical practice, non‐HDL cholesterol, rather than HDL cholesterol, is used to risk stratify patients. On the other hand, extremely high levels of HDL have been associated with high cause mortality in men and women [3,4]. Therefore, we share this interesting case of extremely high HDL levels with its differentials.

A 57-year-old African-American male patient with a history of nephrectomy and dyslipidemia was seen in the outpatient department for his annual checkup. The patient has a history of exceptionally high levels of HDL cholesterol without any symptoms of dyslipidemia. Further examination revealed that his high-density lipoprotein level was once more abnormally high (199 mg/dL). The patient smoked one pack of tobacco each day for 17 years prior to quitting 10 years ago. Additionally, the patient has a history of occasional drinking. The patient has no previous history of taking medications. The patient has a family history of symptomatic dyslipidemia in   his   mother   and  maternal  grandmother but  was  not documented. Vitals upon admission were blood pressure of 124/86 mm Hg and a heart rate of 86 beats per minute. His electrocardiogram showed normal sinus with no ST‐T wave changes.

Further laboratory data showed triglyceride 104 mg/dL (0‐150), total cholesterol 320 mg/dL (107‐200), LDL 100 mg/dL (0-130), HDL 199 mg/dL (23‐92) with repeated level of 199 mg/dL.                

His haemoglobin A1C was 5.8% (0.5.5), TSH was 0.431 uIU/mL (0.554.78), folic acid was more than 24.0 ng/mL (5.3824.0), vitamin B12 was 530.0 pg/mL (2501100) and vitamin D was 15.0 ng/mL. (32-100). Other laboratory results were normal, such as a complete blood count and a comprehensive metabolic panel. His echocardiogram revealed paradoxical septal motion with overall normal LV EF, an estimated left ventricular ejection fraction of 60%, trace mitral valve regurgitation and a Chiari network in the right atrium. Carotid Doppler findings were normal. Recommendations for additional lipidology and genetic testing?

High serum HDL cholesterol levels (>60 mg/dL [1.6 mmol/L]) can be inherited or caused by conditions such as alcohol abuse, hypothyroidism, phenytoin treatment, insulin treatment in type 1 diabetes or regular moderate to vigorous aerobic exercise. It is typically linked to a lower risk of Coronary Heart Disease (CHD) [4]. High HDL cholesterol levels have been linked to an increased risk of atherosclerosis and cardiovascular events in several studies [5]. In these cases, HDL particles' antiatherogenic properties are dysfunctional [6]. Large HDL particles have a lower concentration of anti-inflammatory proteins and lipids, which may explain their dysfunctional properties. However, whether HDL particles are functional in patients with high HDL cholesterol levels remains to be seen. In one series of patients with elevated HDL cholesterol levels who had CHD, it was found that the HDL particles were functionally impaired with regard to antioxidant and anti‐inflammatory activities [5].

Our patient's serum HDL lipoprotein levels were extremely high on four occasions and despite the high HDL levels, he had no evidence of coronary artery disease. It has been reported that his moderate alcohol consumption raises HDL cholesterol levels [7].

Second on our list is CETP deficiency, which is involved in HDL metabolism by mediating the transfer of cholesteryl esters from HDL particles to the triglyceride-rich lipoproteins LDL and Very Low-Density Lipoprotein (VLDL). His elevated HDL levels are likely due to a family history of dyslipidemia. Polymorphisms that affect CETP activity are common, such as isoleucine for valine substitution at codon 405 (I405 V). In one Danish study, for example, 43 percent of those studied were heterozygous for I405V, while 11 percent were homozygous for I405V [8]. Polymorphisms that reduce CETP activity, such as I405 V, typically increase plasma HDL cholesterol concentrations [9-11]. Although we did not test the patient as an inpatient, upon discharge recommendations were for further lipidology and genetic testing as an outpatient.

We present an intriguing case of extremely high serum HDL and how a patient with significant dyslipidemia is asymptomatic despite having abnormal lab values for the past two years. Our patient's serum HDL lipoprotein levels were extremely high on four occasions and despite the high HDL levels, he had no evidence of coronary artery disease. It has been reported that his moderate alcohol consumption raises HDL cholesterol levels. Second on our list is CETP deficiency, which is involved in HDL metabolism by mediating the transfer of cholesteryl esters from HDL particles to the triglyceride rich lipoproteins LDL and Very Low-Density Lipoprotein (VLDL). His elevated HDL levels are likely due to a family history of dyslipidemia.

Ethical Approval

Our institution does not require ethical approval for reporting individual cases or case series.

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