Lipid Profile and Lipoprotein(a) Testing

Abstract

Background

The treatment of dyslipidemias plays a major role in the primary and secondary prevention of cardiovascular disease. Proper evaluation of the patient’s lipid status is very important for risk assessment and as a guide to treatment.

Methods

This review is based on publications retrieved by a selective search of the literature, including current guidelines.

Results

Measurement of the plasma concentration of cholesterol, triglycerides, HDL- and LDL-cholesterol, calculation of the non-HDL cholesterol concentration, and—on a single occasion—determination of the lipoprotein (a) concentration enable the clinician to quantify the lipid-associated health risk and monitor the effects of treatment. These blood tests can be performed in a non-fasting state except in special situations (particularly, hypertriglyceridemia). The HDL quotient is an obsolete measure. The main goal of treatment is to achieve an LDL-cholesterol level adequate to the patient‘s cardiovascular risk through lifestyle modification and, if necessary, medication. A high lipoprotein (a) concentration cannot be lowered with orally administered drugs; above all, patients should lower their LDL-cholesterol levels while minimizing all other risk factors.

Conclusion

Measurement of the concentration of cholesterol, triglycerides, and HDL- and LDL-cholesterol and calculation of the non-HDL-C suffice as a guide to lipid-lowering treatment. The primary therapeutic goal is to lower LDL cholesterol.

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Randomized studies on primary and secondary prevention have shown that LDL-lowering treatment reduces the risk of cardiovascular disease and–where assessed—also cardiovascular mortality and all-cause mortality (1). Lowering of the LDL cholesterol concentration by 1 mmol/L (approximately 40 mg/dL) resulted in a reduction in relative risk for cardiovascular events of 22% (2). The absolute risk reduction and consequently the number needed to treat (NNT) depends largely on the global vascular risk of the patient treated, the baseline cholesterol level, the extent of cholesterol reduction, and the duration of treatment; in primary prevention studies, it varied between 52 (3) and several hundred per year.

The absolute benefit is greatest in patient populations at very high absolute risk, for example, patients with manifest atherosclerosis (2). Thus, clinical decisions with regard to lipid-lowering treatment and its intensity are made on the basis of risk—not on the basis of the lipid profile only. Other than patients with known atherosclerosis, patients with impaired renal function, familial hypercholesterolemia and diabetes are at high or very high risk and usually require intensified drug treatment. In asymptomatic patients between 40 and 89 years of age, the need for treatment is determined using the SCORE2 risk system. In comparison to other risk calculators (SCORE, arriba calculator), SCORE2 offers the advantage that it is based on current data, assesses risk on a country-specific basis and takes greater account of age (4).

In clinical practice, it is very important to establish the lipid status correctly. Firstly, the lipid profile results feed into the risk assessment: total cholesterol, high-density lipoprotein (HDL) cholesterol and lipoprotein (a) [abbreviated Lp(a)]. Second, they can be used to monitor whether the LDL cholesterol and non-HDL cholesterol target levels have been achieved with the treatment, since all current recommendations support a target-oriented approach (1, 5). The target levels are listed in Table 1 (1, 4).

Table 1. Target lipid levels for cardiovascular disease prevention.

	Primary target		Secondary targets
Cardiovascular risk*	LDL-C		Non-HDL-C		ApoB
	mg/dL	mmol/L	mg/dL	mmol/L	mg/dL
Low	<115	<3.0	<145	<3.8	Not defined
Moderate	<100	<2.6	<130	<3.4	<100
High	<70	<1.8	<100	<2.6	<80
Very high	<55	<1.4	<85	<2.2	<65

* Estimation of cardiovascular risk based on clinical parameters as well as the ESC Score2

(Risk of a fatal or nonfatal cardiovascular event within the next 10 years);

“low risk“ with age-dependent risk according to Score2 (age <50 years: <2.5%; 50–69 years: <5%; ≥ 70 years: <7.5%); “moderate risk”, e.g., in case of recent onset of diabetes mellitus without other risk factors or age-dependent risk according to Score2 (age <50 years: <2.5%; 50–69 years: <5%; ≥ 70 years: <7.5%); “high risk“, e.g., in case of diabetes mellitus without end-organ damage or age-related risk according to Score2 (age <50 years: 2.5 to <7.5%; 50–69 years: 5% to <10%; ≥70 years: 7.5% to <15%); “very high risk“, e.g., in case of evidence of atherosclerosis, severely impaired renal function (GFR<30 mL/min) or diabetes mellitus with end-organ damage or age-dependent risk according to Score2 (age <50 years: ≥7.5%; 50–69 years: ≥10%; ≥ 70 years: ≥ 15%) (1, 4).

ApoB, apolipoprotein B; LDL-C, low-density lipoprotein cholesterol;

Non-HDL-C, non-high density lipoprotein cholesterol

The current guideline of the German Federal Joint Committee (G-BA, Gemeinsamer Bundesausschuss) on health checks recommends measuring cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol levels. Furthermore, the additional calculation of non-HDL cholesterol and the one-time measurement of Lp(a) seems to be necessary and useful to correctly assess the lipid-related risk and to verify the effects of treatment (Table 2) (6). All other parameters are reserved for special situations.

Table 2. Major lipid parameters.

Parameter	Clinical significance	Comment
Cholesterol	Cardiovascular risk factor	Summation parameter comprising LDL, HDL, but also cholesterol associated with triglyceride-rich lipoproteins and cholesterol bound to lipoprotein (a)
LDL cholesterol	Causal cardiovascular risk factor	LDL causes direct damage to the blood vessels
HDL cholesterol	Low values risk indicator	Low HDL cholesterol levels are indicative of increased risk; to increase HDL cholesterol does not reduce risk
Triglycerides	Risk factors for cardiovascular disease and acute pancreatitis	Moderate elevation (up to approx. 600 mg/dL; 6.8 mmol/L) increases cardiovascular risk
Non-HDL cholesterol	Cardiovascular risk factor	Summation parameter, covering all cholesterol associated with atherogenic lipoproteins; important in hypertriglyceridemia
Lipoprotein(a)	Risk factor for cardiovascular disease and aortic valve stenosis	Independent, genetic risk factor; is thought to be causally linked to atherosclerosis
Lipid electrophoresis	Simple classification of dyslipidemia	Rarely used today
Apolipoprotein B	Cardiovascular risk factor	Summation parameter, comprises all atherogenic lipoproteins
Additional apoprotein testing	More accurate classification of rare disorders	Determination by lipid specialists
Genetic testing	In situations of clinical uncertainty	Enhances treatment adherence; allows in certain cases use of medications requiring genetic testing
Sitosterol	Diagnosis of sitosterolemia	Determination by lipid specialists

HDL, high-density lipoprotein; LDL, low-density lipoprotein

Basic parameters

Total cholesterol

Total cholesterol comprises LDL cholesterol, HDL cholesterol and cholesterol associated with triglyceride-rich lipoproteins (very-low-density lipoprotein [VLDL] cholesterol or remnant cholesterol).In addition, Lp(a)-associated cholesterol is assessed. With LDL cholesterol being the main component of total cholesterol, total cholesterol correlates well with risk from an epidemiological perspective. However, given that an increase in HDL cholesterol may also be behind an elevated total cholesterol level, assessing overall risk on the basis of total cholesterol is problematic when looking at individual patients. Nevertheless, it is necessary to measure total cholesterol in order to calculate the non-HDL cholesterol component.

LDL cholesterol

A homogenous enzymatic colorimetric assay is typically used to measure LDL cholesterol (direct measurement of LDL cholesterol). The Friedewald formula used in the past relies on fasting blood for testing and is prone to inaccuracy when triglyceride levels are elevated (7). It should be noted, however, that direct LDL cholesterol assays may also produce inaccurate results in low ranges and in the presence of high triglyceride levels (8). Both methods of measuring LDL cholesterol include the Lp(a) cholesterol component.

Each LDL is composed of one apolipoprotein B molecule, other apolipoproteins and a variable number of cholesterol molecules (typically in the form of cholesterol ester). Such variability implies a certain inhomogeneity, with LDLs with particularly low cholesterol (small, dense LDLs) or those with particularly high cholesterol (large LDLs; large buoyant LDL particles) being considered especially atherogenic (9). Here, it should be noted that elevated levels of particularly pathogenic LDL are characteristic of patients with concomitant hypertriglyceridemia or poorly controlled diabetes mellitus (10). Since the evidence for risk reduction by lowering of lipid levels is based on measuring LDL cholesterol (and not its subtypes), it is not recommended to measure the levels of LDL subtypes. The primary goal of treatment is lowering the LDL cholesterol concentration (1).

HDL cholesterol

As with LDL cholesterol, different HDL subfractions can be distinguished which differ in their apolipoprotein composition and also in the amount of cholesterol transported (11, 12). HDL-associated proteins display considerable heterogeneity and can, for example, mediate negative vascular effects in patients with systemic inflammation (13). Low HDL cholesterol levels are indicative of metabolic disorders (especially diabetes) and inflammation and are associated with an increased risk of cardiovascular events (14). The neutral results of interventional studies on HDL increases as well as genetic data have shown that this relationship is not causal. Contrary to earlier assumptions, high HDL-C levels have no protective effect (15). For clinical practice it is important to note that consequently ratios (such as total cholesterol/HDL cholesterol or LDL cholesterol/HDL cholesterol) are obsolete.

Triglycerides

Triglycerides are transported on a number of different lipoproteins (16, 17). The most important triglyceride-transporting lipoproteins are VLDL, chylomicrons and chylomicron remnants (18). The level of triglyceride concentration correlates with the rate of cardiovascular events (adjusted hazard ratio [HR] for myocardial infarction, 1.5–2.0 per 89 mg/dL [1 mmol/L] triglyceride increase) and risk of acute pancreatitis: the adjusted HR for acute pancreatitis is 1.17 (95% confidence interval [1.10; 1.24]) per 89 mg/dL (1 mmol/L) triglyceride increase) (19). Here, it should be noted that the cardiovascular risk does not increase any further beyond a triglyceride level of approximately 5 mmol/L (450 mg/dL), whereas the risk of acute pancreatitis increases continuously and is greatly increased at levels above 11 mmol/L (approximately 1000 mg/dL). The increased cardiovascular risk is not attributable to the triglycerides as such. The pathogenic effect is primarily due to the cholesterol component in triglyceride-rich lipoproteins, the particle as such and the change in LDL and HDL metabolism triggered by the increased concentration of triglyceride-rich lipoproteins (18). Thus, the risk associated with triglyceride-rich lipoproteins can be better estimated based on the cholesterol component (for example, VLDL cholesterol or remnant cholesterol) or based on the apolipoprotein-B level. The cholesterol associated with triglyceride-rich lipoproteins is included in the parameter non-HDL cholesterol (14).

Non-HDL cholesterol

Non-HDL cholesterol is a calculated parameter (total cholesterol minus HDL-C), i.e. no additional analysis costs are incurred. Non-HDL-C totals all cholesterol that is not attributable to HDL (Figure 1), i.e. transported in apolipoprotein-B-containing lipoproteins. In addition to LDL-C and Lp(a), it includes the cholesterol contained in triglyceride-rich lipoproteins. All apolipoprotein B-containing lipoproteins (and presumably only these) are considered to be pro-atherogenic (20). Non-HDL cholesterol is therefore viewed as a global parameter for lipid-associated risk, similar to the apolipoprotein B concentration. The more elevated the serum triglyceride levels, the greater the superiority of non-HDL-C over LDL-C with regard to risk stratification and treatment monitoring. For this reason, it is particularly helpful to look at non-HDL cholesterol in patients with elevated triglyceride levels.

Figure 1.

Allocation lipids – lipoprotein fractions

ApoB, apolipoprotein B; -C, cholesterol; HDL, high-density lipoprotein;

IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; Lp(a); lipoprotein (a); VLDL, very-low-density lipoprotein; TG, triglyceride

Lipoprotein (a)

Concentrations of Lp(a) are reported as either molar concentration (typically in nmol/L) or mass concentration (typically as mg/dL or g/L). Given the considerable variability of Lp(a) size, it is not possible to directly convert molar concentration to mass concentration (21). Furthermore, ethnicity- and sex-related differences in Lp(a) concentrations are found (women have on average 5–10% higher Lp(a) levels than men) (22). Lp(a) concentration does not show a normal distribution in the population, but is significantly shifted to the left. That is, there is a great number of persons with very low Lp(a) levels and a few with excessively high levels. In the Caucasian population, approximately 15% have high Lp(a) levels above 125 nmol/L, while 10% have Lp(a) levels >170 nmol/L and 5% have Lp(a) levels >220 nmol/L (21). Lp(a) levels are largely determined by genetic factors. Furthermore, renal impairment (increases Lp[a] levels) and impaired hepatic function (decreases Lp[a] levels) can also have an effect on plasma concentrations. Nutrition and physical activity have been shown to have no effect, and oral lipid-lowering treatments have little impact on Lp(a) levels. While there is a linear relationship between Lp(a) level and cardiovascular event rate, the following classification is currently used for clinical and practical reasons:

• “not elevated“: <30 mg/dL; <75 nmol/L

• “marginal”: 30–50 mg/dL; 75–125 nmol/L

• “elevated“: >50 mg/dL; >125 nmol/L

Supplementary parameters (based on the clinical situation)

Lipid electrophoresis

This previously widely used method for classifying dyslipidemia is now only rarely used. It still plays a certain role in the diagnosis of type III hyperlipoproteinemia (familial dysbetalipoproteinemia) and the detection of chylomicrons.

Apolipoprotein B

Similar to the non-HDL cholesterol concentration, the plasma concentration of apolipoprotein B is closely correlated with cardiovascular risk. In the light of recent epidemiological studies, it must be assumed that apolipoprotein B is the best risk marker in primary and secondary prevention (23, 24). However, at the individual level, no clinically relevant improvement in risk prediction is achieved compared to non-HDL-C, so routine testing of apolipoprotein B is currently not recommended. Measuring the concentration of apolipoprotein B can be useful in the work-up of an “apparent” increase in LDL concentration in patients with cholestatic liver disease. If apolipoprotein B levels are also elevated in this situation, this is indicative of a true elevation of atherogenic lipoproteins. If the apolipoprotein B concentration is discordant with the LDL cholesterol concentration, it indicates the presence of abnormal lipoproteins, a typical finding in cholestasis (25).

Additional apolipoprotein testing

In exceptional cases (extreme hypo- or hyperlipoproteinemia), it can be useful to also measure the levels of other apoproteins (apo-A-I, apo-A-II, apo-E, apo-C-III, etc.) to enable a more precise classification of the dyslipidemia. The results should be interpreted by lipid specialists.

Genetic testing for familial hypercholesterolemia

Usually, the diagnosis is established on the basis of clinical findings, including the level of LDL cholesterol (>200 mg/dL; 5 mmol/L), the family history and cutaneous manifestations. The cardiovascular risk is mediated by LDL-cholesterol phenotype rather than genotype. Genetic testing is useful when biological parents are unknown, when the characteristic phenotype of familial hypercholesterolemia only develops later in life, and when it helps to implement treatments (e.g., in affected children, adolescents or young adults) (26, 27).

Genetic testing for familial chylomicronemia syndrome

Severe hypertriglyceridemia (triglyceride levels >1000 mg/dL [11 mmol/L]) is usually due to genetic predisposition in combination with secondary factors (diabetes mellitus, overweight, alcohol consumption, medication). Rarely, severe hypertriglyceridemia is caused by familial chylomicronemia syndrome: always triglyceride levels >1000 mg/dL, frequently a history of pancreatitis, no secondary triggers of hypertriglyceridemia. The diagnosis is confirmed by genetic testing. The management of these patients is in the hands of specialized outpatient clinics (28, 29).

Apolipoprotein E genotyping or phenotyping

The purpose of this test is to rule out familial dysbetalipoproteinemia (previously type III hyperlipoproteinemia). This should be considered when cholesterol and triglyceride levels are concomitantly elevated (typically 250–400 mg/dL) and LDL cholesterol levels fluctuate widely at the same time. Since cholesterol levels fluctuate considerably, non-HDL cholesterol is a better parameter to estimate the associated increased risk of atherosclerosis and guide treatment (30). Here again, it is helpful to have lipid specialists involved in care provision.

Determining sitosterol and other phytosterols

The purpose of determining sitosterol and other phytosterols is to rule out the rare disease of sitosterolemia. The phenotype of sitosterolemia typically resembles that of homozygous familial hypercholesterolemia (xanthomas, coronary heart disease, aortic valve calcification), with the LDL cholesterol level being elevated, but usually not as high as in homozygous familial hypercholesterolemia. Since sitosterolemia responds well to treatment with ezetimibe, it is an import differential diagnosis of familial hypercholesterolemia (31).

Sample collection conditions

Ideally, a patient’s lipid status should be determined under steady-state conditions. All lipoproteins and lipids reach a new equilibrium 4–6 weeks after a change (for example, weight reduction, dietary change, pharmacotherapy). Consequently, a detailed evaluation of any intervention is only useful once this period has elapsed. This also applies to the situation after an acute event (e.g., extensive surgery, acute myocardial infarction). Under such circumstances, lipid levels may be decreased or increased compared to the steady-state condition. For this reason, the lipid status should be reassessed after a few weeks, irrespective of the treatment provided, in order to make changes to the regimen, if necessary.

For a long time, it was a dogma in lipidology that fasting blood levels should be assessed. Nowadays, lipid levels may also be measured in a nonfasting state, provided that there is no hypertriglyceridemia and LDL cholesterol is measured directly or by ultracentrifugation (Box) (32).

Box. Indications for measuring triglycerides in fasting blood according to (32).

• Non-fasting triglyceride levels >440 mg/dL (5 mmol/L)

• Known hypertriglyceridemia

• After hypertriglyceridemia-associated pancreatitis

• Prior to start of medications which may cause hypertriglyceridemia

• When other tests require fasting blood collection (e.g. blood glucose testing or drug-level testing)

Interpretation

Lipid levels are usually measured to assess the risk of a cardiovascular event and must be interpreted in the context of the presence of other risk factors. Helpful in this regard is the classification proposed by European medical societies of various disciplines (cardiology, atherosclerosis, diabetology) which distinguishes persons at very high, high, moderate, and low risk (1). From this classification, LDL cholesterol targets (primary target) and non-HDL cholesterol targets (secondary target) are derived (Table 1). Once the individual LDL cholesterol target has been established, lifestyle modification, statins, ezetimibe, bempedoic acid, and PCSK9 inhibitors should be used for treatment. Endpoint studies evaluating these treatment strategies have shown that the LDL cholesterol reduction induced by these measures translates into a relevant risk reduction (1). Most recently, this was shown in a study on bempedoic acid with 13 970 statin-intolerant patients (HR 0.87; p = 0.004; absolute risk reduction 1.6%) (33).

Since observational studies have shown that especially patients at very high risk fail to reach their targets, experts have advocated the early (initial) use of combination therapies in very-high risk patients who are clearly far from target levels, analogous to the principles applied in the treatment of hypertension (Figure 2) (34– 36). While the management of elevated LDL cholesterol levels is rather clearly defined, there is still uncertainty as to the management of elevated Lp(a) levels, since interventional studies are still missing. Thus, essential practical aspects of Lp(a) testing will be summarized in the following.

Figure 2.

Possible treatment algorithm to achieve the LDL cholesterol target

*¹LDL targets according to ESC and EAS are listed in Table 2; *²In acute coronary syndrome, a significant decrease should be induced as soon as possible; re-evaluation after 4–6 weeks is useful; *³typically high-dose atorvastatin (40 mg/d) or rosuvastatin (20 mg/d or 40 mg/d); *⁴Only in case of very high risk and a marked gap to the target (prescription restriction must be considered);

ESC, European Society of Cardiology; EAS, European Atherosclerosis Society; LSM, lifestyle modification

Elevated lipoprotein (a) levels

Epidemiological and genetic studies have shown that there is a causal relationship between elevated Lp(a) levels and cardiovascular morbidity and mortality: HR 1.11 (1.10; 1.12) per 50 nmol/L increase. Markedly elevated Lp(a) levels (>168 nmol/L; 90^th percentile) are associated with a three- to fourfold increased rate of myocardial infarction (22, 37). Data from the UK Biobank of more than 415 000 persons of European descent show that failure to consider Lp(a) concentrations may result in a relevant miscalculation of risk. For example, the lifetime risk of a cardiovascular event for a person with a baseline risk of 5%, excluding Lp(a), increases absolutely by 1.1% to 6.6% when Lp(a) is 30 mg/dL rather than 7 mg/dL, and by 3.3% to 8.3% when Lp(a) is 75 mg/dL. For a person with a baseline risk of 25%, the corresponding absolute risk increase is 5.5% (to then 30.5%) and 9.9% (to then 34.9%), respectively (21). The discussion as to how an elevated level should be incorporated into risk scores is still ongoing. In addition to cardiovascular events, aortic valve stenosis, cardiovascular mortality and all-cause mortality are associated with elevated Lp(a) concentrations (21, 38, 39). With increasing levels, there is a continuous increase in risk. Even though Lp(a) contains a thrombogenic component, genetic variants causing elevated Lp(a) levels are not associated with venous thrombosis events or embolism.

Given the strong genetic determinant of Lp(a) concentrations, family screening is an important implication of elevated Lp(a) levels. In patients with high Lp(a) levels and premature atherosclerosis, e.g., myocardial infarction at a young age, it is reasonable to already screen the children (21).

Since no effective specific therapy is currently available to lower Lp(a) levels, the focus is on optimizing the control of other risk factors (Figure 3). In addition to not smoking, lowering LDL cholesterol levels to risk-specific targets is key (21).

Figure 3.

Recommended management of patients with elevated lipoprotein (a) levels

LDL, low-density lipoprotein; Lp(a), lipoprotein (a)

PCSK9 inhibitors can lower Lp(a) levels by 20–25%. However, it is unknown how such lowering of Lp(a) levels translates into a reduction in the risk for cardiovascular disease. Regular lipoprotein apheresis treatment may be an option to be discussed in patients with progressive atherosclerotic disease despite optimal control of all other risk factors as well as lipoprotein (a) levels of >60 mg/dL. This extracorporeal procedure can lower Lp(a) levels by approximately 60–70% per session (duration of 2–4 hours), resulting in mean reductions of 30–50% with weekly apheresis, taking rebound kinetics into account. (40). However, there are no randomized endpoint studies on lowering of Lp(a) levels by apheresis treatment available as yet.

In addition, specific drugs (small interfering RNA) are being developed that can lower Lp(a) levels by 80% and more (e1). These drugs are currently being evaluated in large endpoint trials, with initial results expected to be available in 2025.

Questions on the article in issue 35–36/2023:

Lipid Profile and Lipoprotein (a) Testing

The submission deadline is 21 August 2024. Only one answer is possible per question.

Please select the answer that is most appropriate.

Question 1

What does the abbreviation LDL stand for in the text?

1. Low-density lipoprotein

2. Long-duration lipoprotein

3. Low-density lipids

4. Lipid-disease lipoprotein

5. Low-density lipopolysaccharides

Question 2

Which of the following blood test parameters cannot be effectively lowered using oral medication?

1. LDL

2. Cholesterol

3. Lipoprotein(a)

4. Triglycerides

5. Blood sugar

Question 3

Which of the following parameters is not included in the German Federal Joint Committee’s recommendation for lipid status basic screening?

1. Cholesterol

2. Triglycerides

3. HDL cholesterol

4. Sitosterol

5. LDL cholesterol

Question 4

The SCORE2 risk system is used to estimate cardiovascular risk for which population of patients?

1. Symptomatic patients aged between 50 and 70 years

2. Asymptomatic patients aged between 40 and 89 years

3. Symptomatic and asymptomatic patients of any age

4. Symptomatic and asymptomatic patients aged between 60 and 90 years

5. Asymptomatic patients aged between 40 and 65 years

Question 5

Which statement about effects on lipoprotein (a) levels is true?

1. Lipoprotein (a) levels may be increased due to impaired renal function.

2. Lipoprotein (a) levels may be increased due to impaired hepatic function.

3. Lipoprotein (a) levels are largely independent of genetic factors.

4. Lipoprotein (a) levels are is largely determined by diet.

5. Lipoprotein (a) levels are considerably reduced by moderate physical activity.

Question 6

Which of the following blood components is not a triglyceride-rich lipoprotein?

1. Chylomicrons

2. VLDL

3. Chylomicron remnant

4. IDL

5. HDL

Question 7

After an intervention or an event (e.g., drug therapy, weight loss, myocardial infarction), how long does it usually take until the lipid status has returned to a steady state?

1. 12–24 hours

2. 4–6 days

3. 1–2 weeks

4. 4–6 weeks

5. 3–4 months

Question 8

In cardiovascular disease prevention by means of intervention in lipid metabolism, which parameter does the primary treatment goal address?

1. Lowering of LDL cholesterol levels

2. Stabilization of HDL cholesterol levels

3. Reduction of lipoprotein (a) levels

4. Increase in apolipoprotein B levels

5. Increase in VLDL levels

Question 9

Which of the following drugs is not used to lower LDL cholesterol levels?

1. Ezetimibe

2. Bempedoic acid

3. Memantine

4. PCSK-9 inhibitors

5. Statins

Question 10

Which of the following drugs can lower lipoprotein (a) levels by 20–25%?

1. Ezetimibe

2. Statins

3. Bempedoic acid

4. PCSK-9 inhibitors

5. Imatinib